The Department of Internal Medicine’s commitment to the career development of young physicians and academic mission to pursue novel disease prevention and treatment strategies has led to the development of the Physician-Scientist Training Program (PSTP) in 2013. This program merges the outstanding clinical training provided by the Department of Internal Medicine with an intensive mentorship program focused on development of essential skill sets for the physician scientist.
Trainees have the opportunity to participate in one of eight existing T32 training programs within the medical center, access to a multidisciplinary mentorship team, access to didactics and workshops within the Center for Clinical and Translational Research (CCTS) and financial support for career development activities.
Goals of the PSTP are to provide a combined training experience in internal medicine and subspecialty of choice with a focus on linking trainees with post graduate research mentors. Emphasis is placed on optimizing career development to transition efficiently into an independently funded faculty position. The overarching goal of the program is to produce outstanding physician scientists who are committed to the pursuit of an independent academic career pathway. Trainees have transitioned into tenured track positions each with fully funded laboratory programs.
Internal medicine training: 24 months
Subspecialty training: 12-24 months (dependent on subspecialty)
Research training (80%): 36 months
Ambulatory Clinic during research training: ½ day per week
For select, qualified candidates, option to join faculty during last year of training (as instructor or assistant professor). Targeted ABIM Internal Medicine Board Eligibility: PGY 4. Targeted ABIM Subspecialty Board Eligibility: PGY 5 or 6 (depending on subspecialty).
PSTP Career Development Supplements are provided during PGY 1-6:
Internship $4,000 support for travel to a national meeting, journals
Junior Residency $4,000 support for travel to a national meeting, journals Year Three
Clinical Fellowship $4,000 support for a computer and software, travel to a national meeting, journals Years Four - Six Research
$15,000 $10,000 to supplement salary; $5,000 to support travel and other expenses
- Trainees who have performed exceptionally well (K award or equivalent and impactful publications), have the option in the last year of program (PGY5 or 6 depending on subspecialty) for negotiating full-time faculty position (instructor vs. assistant professor per division's discretion).
- Assistance targeting extra/intra mural grants (including NIH loan repayment program)
- For categorical candidates who do not participate in the ABIM research pathway, there are opportunities to pursue an extended research block
- A new International Scholars Track will be piloted in 2022
PSTP curriculum: Meetings for special topics or research in progress for candidates in research years. Specialized topics include pursuit of funding (K and first time R01 workshops), career planning and negotiating job positions, commercializing discoveries, CCTS/Fisher College of Business Innovation Workshop, engaging in development and philanthropic activities, communicating your science to the public, preparing for presentations, mentorship, how to run a lab, etc.).
Obtain mentorship skills: Regular interaction with MSTP program providing mentorship to graduate student trainees to aid in transition to a residency within a PSTP
Career development activities in our Center for Clinical and Translational Science (CCTS)
Present your research: Participate in the annual departmental research meeting and others
Individuals who hold an MD or PhD degree or an MD degree with significant research experience are eligible for the PSTP Research Pathway. Categorical residents interested in obtaining extended research blocks will be invited to submit an application outlining scope of the research project, timeline and mentorship information. Eligible candidates will be invited for an interview with the department, faculty within subspecialty of interest and the PSTP director. Questions regarding eligibility can be sent directly to Dr. Robert Baiocchi Robert.Baiocchi@osumc.edu.
Please note that we have a separate rank list for our PSTP track. When applying through ERAS, please look for the “Internal Medicine-Research Track” to apply directly to the PSTP track. The code to rank the PSTP track on the NRMP is 1566140C1. Please note that you can use NRMP code 1566140C0 if you want to be considered for the categorical program as well as ranking the PSTP track with its NRMP code.
Faculty and TraineesWe have an established track record of our trainees advancing to tenured track positions in academic medicine programs. Our trainees leave the program funded and join faculty positions. Thus far, most trainees have obtained independent funding and have accepted competitive laboratory packages to begin their careers as a physician scientist.
Leadership and PSTP Alumni
Robert Baiocchi, MD, PhD
Assistant Program Director for Research, Director, Physician-Scientist Training Program
MD: The Ohio State University
PhD: State University of New York at Buffalo
Residency: The Ohio State University
Fellowship: The Ohio State University
Lapo Alinari, MD, PhD
Assistant Professor of Internal Medicine
Clinical interests: Lymphoma
Research: Experimental Therapeutics in Lymphoid Malignancies
MD: University of Florence, Italy
Residency/Fellowship: The Ohio State University
Nicole Grieselhuber, MD, PhD
Assistant Professor of Medicine
My current research interests include molecular mechanisms of leukemogenesis, pharmacology of targeted inhibitors and the application of genomic technologies to patient care.
Ann-Kathrin Eisfeld, MD
PSTP Trainee, PGY2
The James Cancer Center, the incredibly enthusiastic and supportive faculty in the Divisions of Hematology and Oncology, and the rich campus diversity, made OSU my top choice among all PSTP training programs.
Courtney Campbell, MD, PhD
Cardio Oncology Fellow at Washington University
Francesca Cottini, MD
Dimitrios Papaioannou, MD
Dionisia Quiroga, DO, PhD
PSTP Trainee, PGY2
I became interested in medicine at a young age through my father, a local OB/GYN. After completing my BS in physiology with a specialization in bioethics, I was accepted into Michigan State University's D.O./Ph.D Physician Scientist Training Program.
Caner Saygin, MD
Our PSTP Trainees
Hyunwoo (Tony) Kwon, MD, PhD PGY-1
I was born and raised in Seoul, South Korea, until I was 11 years old when my family moved to Canada. My first research experience came as a high school student in the microbiology laboratory of Dr. John McCormick at Western University in London, Canada, where I characterized the antimicrobial activity of fresh garlic extract against Group A Streptococcus. As an undergraduate student in the immunology specialist program at the University of Toronto, I continued to pursue my passion for discovery in the cell biology laboratory of Dr. John Brumell at SickKids Hospital, investigating host-pathogen interactions by using Salmonella and Listeria as model organisms. During these 4 years, I also learned through clinical volunteering opportunities how incredibly rewarding it is to witness physical and emotional transformations that occur to patients and their loved ones upon healing. Given my passion for both scientific investigation and clinical practice, I decided to pursue a career as a physician-scientist.
In 2014, I moved to the US to join the Medical Scientist Training Program at the Medical University of South Carolina (MUSC). During my training, I became drawn to medical oncology as a meaningful profession that entails close interactions with patients, with the responsibility and privilege to have a fundamental impact on their lives. It also embodies opportunities for multidisciplinary collaboration and active research participation to provide the best evidence-based care. There has never been a more exciting time in medical oncology as several decades of basic science research are translating to increasing success in treating or palliating patients with advanced disease. I am particularly passionate about Immuno-Oncology, which represents one of several advances that have revolutionized cancer therapy.
I completed my graduate dissertation under the mentorship of Dr. Zihai Li, who was previously at MUSC and now is the founding director of Pelotonia Institute for Immuno-Oncology (PIIO) at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). Based on our investigation of sexual dimorphism in cancer immunity, we demonstrated that androgen promotes dysfunction of CD8+ T cells – often referred to as cancer “killer” cells – in the tumor microenvironment. Our findings provide an important immunological mechanism underlying the male-biased incidence and mortality of various cancers and highlight androgen as a new target for cancer immunotherapy.
My long-term career goal is to utilize the “bedside-bench-bedside” approach of using clinical findings to facilitate mechanistic investigations that will help drive immunotherapy breakthroughs towards cancer cures. I am excited to join the Ohio State’s Physician Scientist Training Program that simultaneously provides extensive clinical training, clear research support and intensive mentorship – all focused on the development of physician scientists. Given my goals, Ohio State is clearly a special place for its community-level commitment to Immuno-Oncology. As I look forward to my next chapter in my training, I feel confident that I have the experience, curiosity, and most of all, compassion to assist patients in need and contribute to our fundamental understanding of cancer immunology.
When I am not working, I enjoy spending time with my fiancé, family, and friends, as well as travelling and exploring local breweries and coffee shops.Education
MD, Medical Scientist Training Program, MUSC, 2022
PhD, Medical Scientist Training Program, MUSC, 2022
BS, University of Toronto, 2014
Canadian Institutes of Health Research Doctoral Research Award – Doctoral Foreign Study Award (Ranked in top 2%), May 2019
Hollings Cancer Center Graduate Fellowship, March 2018
Korean Canadian Scholarship Foundation Award (Ph.D. Category), May 2018
APSA Excellent Mentor Award, May 2017
Abney Foundation Scholarship, MUSC Hollings Cancer Center, Jul 2015, 2016
Canada’s Top 20 Under Twenty Award, Youth in Motion, Apr 2010
Kwon H, Schafer JM, Song NJ, Kaneko S, Li A, Xiao T, Ma A, Allen C, Das K, Zhou L, Riesenberg BP, Chang Y, Weltge P, Velegraki M, Oh DY, Fong L, Ma Q, Sundi D, Chung D, Li X and Li Z. 2022. Androgen Conspires with the CD8+ T Cell Exhaustion Program and Contributes to Sex Bias in Cancer. Sci Immunol. First Release. PMID: 35420889
Schafer JM, Xiao T, Kwon H, Collier K, Chang Y, Bolyard C, Chung D, Yang Y, Sundi D, Ma Q, Theodorescu D, Li X, and Li Z. 2022. Sex-Biased Adaptive Immune Regulation in Cancer Development and Therapy. Submitted to special issue entitled "Sex Differences in Cancer” in iScience.
Salem M, Wallace CH, Velegraki M, Li A, Ansa-Addo EA, Metelli A, Kwon H, Riesenberg B, Wu BX, Zhang Y, Guglietta S, Sun S, Liu B, and Li Z. 2019. GARP Dampens Cancer Immunity by Sustaining Treg Cell Function and Driving their Accumulation in the Colon. Cancer Res. 79(6):1178-1190. doi: 10.1158/0008-5472.CAN-18-2623. PMID: 30674536.
Kwon H, Lin CY, Chung D, Li X, and Li Z. 2018. Sex as a predictor of response to cancer immunotherapy – Correspondence to “Cancer Immunotherapy Efficacy and Patients’ Sex: A Systematic Review and Meta–analysis”. Lancet Oncol. 19(8):PE379. DOI: https://doi.org/10.1016/S1470-2045(18)30445-5.
Lin CY, Kwon H (co–first author), Rangel–Rivera GO, Li X, Chung D, and Li Z. 2018. Sex Differences in Using Systemic Inflammatory Markers to Prognosticate Patients with Head and Neck Squamous Cell Carcinoma. Cancer Epidemiol Biomarkers Prev. 27(10):1176-1185. PMID: 30049843.
Liu X, Kwon H (co–first author), Li Z and Fu YX. 2017. Is CD47 an Innate Immune Checkpoint for Tumor Evasion? J Hematol Oncol. 10(12). PMID: 28077173.
Fattouh R, Kwon H (co–first author), Czuczman MA, Copeland JW, Pelletier L, Quinlan ME, Muise AM, Higgins DE, and Brumell JH. 2015. The Diaphanous–related Formins Promote Protrusion Formation and Cell–to–Cell Spread of Listeria monocytogenes. J Infect Dis. 211(7):1185–95. PMID: 25281757.
Roppenser B, Kwon H, Canadien V, Xu R, Devreotes PN, Grinstein S, and Brumell JH. 2013. Multiple host kinases contribute to Akt activation during Salmonella infection. PLoS One. 8(8):e71015. DOI: 10.1371/journal.pone.0071015.
Selected posters and oral presentations
Kwon H, Schafer JM, Song NJ, Kaneko S, Li A, et al. T cell intrinsic androgen signaling contributes to sex-biased CD8+ T cell dysfunction in the tumor microenvironment. AAP/ASCI/APSA Joint Meeting. April 2022. Chicago, USA.
Kwon H and Li Z. Sex Differences in CD8+ T Cell Programming in the Tumor Microenvironment. Bladder Cancer Advocacy Network (BCAN) Think Tank: Biological Basis of Sex Disparities breakout session. Aug 2020 cancelled due to COVID19; Aug 2021. Virtual. Invited Speaker.
Kwon H. Immunological Basis for Sex Differences in Bladder Cancer. Pelotonia Institute for Immuno-Oncology (PIIO) Research in Progress Meeting. July 2019. Columbus, USA.
Kwon H, Kaneko S, Lin CY, Li A, Salem M, et al. Mechanisms Underlying Sex Discrepancy in Bladder Cancer Outcome. Perry V Halushka 2018 MUSC Research Day. Nov 2018. Charleston, USA.
- Awarded 1st place in “PhD VI: Oral Presentation Category” – Willard and Betty Peterson Award
Kwon H, Kaneko S, Lin CY, Li A, Salem M, et al. Identifying Immunological Basis for Bladder Cancer Sex Bias. 28th Annual MUSC MSTP Research Day. Oct 2018. Charleston, USA.
Kwon H, Lin CY, Rangel Rivera GO, Kaneko S, Wallace C, et al. Mechanisms Underlying Sex Discrepancy in Bladder Cancer Outcome. 27th Annual MUSC MSTP Research Day. Dec 2017. Charleston, USA.
Kwon H, Lin CY, Rangel Rivera GO, Kaneko S, Wallace C, et al. Mechanisms Underlying Sex Discrepancy in Bladder Cancer Outcome. Perry V Halushka 2017 MUSC Research Day. Nov 2017. Charleston, USA. o Awarded 1st place in “PhD IV: Years 1–2 Oral Presentation Category”
Briana To, DO, PhD PGY-1
I was born and raised in sunny San Jose, California. After high school, I moved to the small beach town of Santa Cruz to begin my undergraduate studies at the University of California Santa Cruz (Go Banana Slugs!) I thought I would follow in my father’s footsteps as a computer programmer, however I quickly discovered my greatest interest was in biology. Unsure of what I wanted to do with a potential biology degree, I decided to explore research and joined the laboratory of Dr. Philip Berman as a research assistant. The Berman lab focused on developing an effective HIV-1 vaccine by studying antigen processing and presentation of virus envelope proteins.
After three exciting years in an academic research lab, I became interested in experiencing research in industry. Following graduation, I took a position as a research assistant in the department of Pharmacokinetics at Genentech. My team and I focused on an ophthalmologic drug used to treat macular degeneration and diabetic retinopathy. I worked on increasing the half-life of the drug through molecular and chemical modifications and developed and optimized pharmacokinetic assays.
While deciding between medical school or graduate school, I realized that I enjoyed aspects of both fields and ultimately decided to pursue a dual degree program. After over a year at Genentech, I moved to Michigan to join the DO-PhD program at Michigan State University. Although I have worked in various areas of research, I was most drawn to the field of breast cancer research. I chose to join the laboratory of Dr. Eran Andrechek because I was interested in integrating bioinformatics, molecular techniques and animal models. My dissertation focused on characterizing mammary gland development and tumor formation in a novel mouse model of breast cancer. I would like to continue pursuing this integrative research to understand cancer modeling, metastasis, drug resistance and the tumor microenvironment.
In my free time, I enjoy spending time with my pets: Maynard (the corgi), Bear and Bunji (the bunnies), and Siggy (the cat). I also enjoy exploring new restaurants and trying new foods from around the world.
Kristin Weeks, MD, PhD PGY-1
After growing up in a small, rural town outside of Buffalo, NY, I attended the Syracuse University Renée Crown University Honors Program as a Coronat Scholar. There, I earned my Bachelors of Science majoring in biology, sociology, and political science. After a year spent training as an EMT and working as a sexual assault crisis response advocate in Brooklyn, NY, I joined the Medical Scientist Training Program (MSTP) of The Carver College of Medicine at The University of Iowa. I earned a Doctorate of Medicine as well as a Doctorate of Philosophy in Epidemiology and a graduate certificate in Biostatistics through the University of Iowa College of Public Health. The focus of my doctoral work was chronic disease/cancer outcomes and health disparities research. My PhD thesis, “Gynecologic Oncologist Involvement in Rural Ovarian Cancer Patient Care: Exploring Disparities in Surgery, Chemotherapy, and Survival Outcomes in the Midwestern United States,” investigated disparities in rural ovarian cancer care in the Midwestern United States for a special CDC investigation of Midwestern State Cancer Registry patients, and formed interventions to reduce disparities in ovarian cancer care delivery in Iowa. During my Doctorate of Medicine studies, I completed four distinction programs through The Carver College of Medicine graduating with distinction in teaching, humanities, service, and healthcare delivery science, management, and policy.
Pursuing the next phase of my training through the Physician Scientist Training Program at The Ohio State University was an easy choice. The program offers outstanding internal medicine residency training with balanced development of inpatient and outpatient care, exceptional hematology and oncology fellowship training at a world-renown cancer hospital (The James Cancer Hospital), and an unmatched epidemiology research opportunity through the College of Public Health, the Comprehensive Cancer Center and Cancer Control Program. Furthermore, I share the core goals of caring for community by conducting epidemiology research across the cancer control continuum. I am excited to be moving to Columbus, a vibrant big city with a comfortable neighborhood feel, fantastic restaurants and entertainment, and beautiful parks and running trails. ion for Cancer Research Annual Meeting, April 8-13, 2022, in New Orleans, LA
Sayan Mullick Chowdhury, DO, MS, PhD PGY-2
I was born and grew up in Kolkata on the eastern part of India and finished my undergraduate degree in Human Physiology and master’s degree in Biochemistry from University of Calcutta before coming to US to start my PhD at Stony Brook University. My research during PhD was completed at the Multifunction Nano Biosystems Laboratory in the Department of Bioengineering at Stony Brook University where I learnt the basics of tissue engineering and nanobiology. My primary research focus was development of nanoparticle based targeted drug delivery and imaging probes for tumors over-expressing epidermal growth factor receptors (EGFR). As part of my doctoral thesis, I developed nanoparticles that can target EGFR and showed high uptake and chemotherapeutic drug delivery in tumors over-expressing these receptors through an actin dependent micropinocytosis like process. As an offshoot of this work, I also identified how the human papilloma virus (HPV) protein E5 interacts with EGFR to increase uptake of these particles. In a separate project, I also utilized the same nanostructures for the sustained release of the drug lucanthone for effective inhibition of the APE- 1(Human apurinic/apyrimidinic endonuclease 1) gene in glioblastoma. Furthermore, while at Stony Brook I have also helped develop a nanoparticle-based MRI contrast agent for targeted imaging of solid tumors.
While finishing my doctoral thesis work at Stony Brook, I was presented the opportunity to work in the Translation Molecular Imaging Lab at Stanford University to develop an ultrasound imaging guided protocol for safe and effective delivery of biodegradable nanoparticles into Hepatocellular Carcinoma. The project had particular focus on miRNA delivery for modulation of the HCC tumor microenvironment. As part of this project, I developed a nanoparticle-based miRNA delivery platform that can be guided using ultrasound imaging into HCC. I successfully tested the platform in both large and small animal models. During my time at Stanford, I was offered both NIH Stanford Molecular Imaging Scholarship and the NCI Stanford Cancer Imaging Training Award. My research was also awarded the World Molecular Imaging Congress Trainee Travel award thrice (2015-2017) and World Molecular Imaging Congress Late Breaking Abstract Travel Award (2017). My talk at World Molecular Imaging Congress 2017 was also presented the “Best Pre-clinical Paper Award”. I was the only researcher from Stanford University chosen for the Radiological Society of America “Introduction to Academic Radiology for Scientists” Program in 2016. As part of the Stanford Molecular Imaging Scholarship, I was given the opportunity to shadow and work with several physicians including several hematologists and oncologists. It was at this time that I realized my passion for medicine and decided to transition to medical school. I was accepted to Ohio University and continued my medical education on their Dublin (Columbus) Campus. While in medical school, I did two hematology clerkships which I found highly interesting and decided to explore the field further.
I started working with Dr Lalit Sehgal, PhD at Ohio State University to explore the basic research aspect of hematology and worked with Dr Naren Epperla, MD to experience the clinical aspects of the field. My research while in medical school was mainly focused on developing a bone marrow microenvironment mimicking biodegradable scaffold that can be used to study different hematological malignancies. When it came to choosing my residency program, I chose OSU PSTP because during interview day I felt everyone was very welcoming. Almost everyone I interviewed with was very enthusiastic about the great collaborative environment at OSU and spoke about the help and support that is available to ensure that every resident/fellow finds success.
As I continue my journey through residency, I am continuing to experience the wonderful learning environment that OSU fosters. In the future, I want to finish my fellowship in hematology/oncology and continue my research developing scaffold-based 3D models that mimic the bone marrow microenvironment to provide more tools to study hematological malignancies.
Honors and Awards
- Awarded OUHCOM Outstanding Research Award, 2021
- Awarded National Medical Student Researcher of the Year (2019-2020) AACOM Awards 2019, Washington DC
- Awarded Trainee Research Travel Award (Midwest Clinical and Translational Research Meeting) (2020)
- OUHCOM Admissions Scholarship (2018-2019)
- Awarded the World Molecular Imaging Society LBA Student Award (2017)
- Awarded the World Molecular Imaging Society Student Travel Award (2017)
- Awarded the World Molecular Imaging Society Student Travel Award (2016).
- Awarded World Molecular Imaging Society Best Pre-Clinical Paper Award at World Molecular Imaging Congress (2016).
- Awarded the Introduction to Academic Radiology for Scientists Scholarship by Radiological Society of North America (RSNA) (2016). (Only researcher nominated from Stanford University)
- Awarded the National Institutes of Health Stanford Molecular Imaging Fellowship (R25) (2015)
- Mullick Chowdhury S, Daniel Dedora, Balaji Sitharaman, Lilliane Mujica-Parodi. Near-Infrared Spectroscopy and Optical Reporter. US Patent WO/2014/026113
- Mullick Chowdhury S, Balaji Sitharman. Carbon Material Delivery System and Metho
- Mullick Chowdhury S, Lalwani G, Zhang K, Yang JY, Neville K, Sitharaman B. Cell specific cytotoxicity and uptake of graphene nanoribbons. Biomaterials. 2013; 34:283-93.
- Mullick Chowdhury S, Kanakia S, Toussaint JD, Frame MD, Dewar AM, Shroyer KR, Moore W& Sitharaman B. In vitro Hematological and In vivo vasoactivity assessment of dextran functionalized graphene. Scientific Reports .2013; 3: 2584
- Kanakia S, Toussaint JD, Mullick Chowdhury S, Lalwani G, Tembulkar T, Button T, Shroyer KR, Moore W & Sitharaman B. Physicochemical characterization of a novel graphene-based magnetic resonance imaging contrast agent.2013 International Journal of Nanomedicine. 8, 2821–2833.
- Mullick Chowdhury S, Manepalli P, Sitharaman B. “Graphene Nanoribbons Elicit Cell Specific Uptake and Delivery via Activation of EGFR Enhanced by HPVE5” Acta Biomaterialia, 2014, 10.10: 4494-4504.
- Mullick Chowdhury S, Dasgupta S, Mcelroy A, Sitharaman B “Structural disruption increases toxicity of graphene nanoribbons” Journal of Applied Toxicology 34.11 (2014):1235-1246.
- Mullick Chowdhury S, Surhland C, Sanchez Z, Chaudhary P, Suresh Kumar MA, Lee S, Peña LA, Waring M, Sitharaman B and Naidu M. “Graphene Nanoribbons as a Drug Delivery Agent for Lucanthone Mediated Therapy of Glioblastoma Multiforme. Nanomedicine: Nanotechnology, Biology and Medicine 11.1 (2015): 109-118.
- Frame MD, Dewar AM, Mullick Chowdhury S, Sitharaman B. Vasoactive Effects of Stable Aqueous Suspensions of Single Walled Carbon Nanotubes in Hamsters and Mice.2014. Nanotoxicology. 8.8:867-875.
- Kanakia S, Toussaint J, Mullick Chowdhury S, Tembulkar T, Lee S, Jiang Y, Lin R, Shroyer KR, Moore W, Sitharaman B “Dose Range Finding, Acute Toxicity and Safety Pharmacology of Intravenously Administered Functionalized Graphene Nanoparticle Formulations” Biomaterials 35.25 (2014): 7022-703.
- Mullick Chowdhury S, Fang J, Sitharaman B. “Interations of Graphene Nanoribbons with components of the blood vascular system” Future Science OA, (0) 1-17, 2015.
- Wang, TY, Choe JW, Pu K, Devulapally R, Bachawal S, Machtaler S, Mullick Chowdhury S et al. "Ultrasound-guided Delivery of microRNA Loaded Nanoparticles into Cancer." Journal of Controlled Release 203, 99-108. (2015)
- Kanakia S, Toussaint J, Hoang DM, Mullick Chowdhury S, Lee S, Button T, Shroyer KR, Moore W, Sitharaman B, Wadhgiri YZ. “Towards an Advanced Graphene-Based Magnetic Resonance Imaging Contrast Agent: Sub-acute Toxicity and Efficacy Studies in Small Animals.” Scientific Reports (5) 2015
- DeDora DJ, Suhrland S, Goenka S, Mullick Chowdhury S, Lalwani G, Mujica-Parodi LR, Sitharaman B “Sulfobutyl Ether β-Cyclodextrin (Captisol®) and Methyl β-Cyclodextrin Enhance and Stabilize Fluorescence of Aqueous Indocyanine Green. Journal of Biomedical Materials Research: Part B-Applied Biomaterial, Aug 6, 2015.
- Mullick Chowdhury S, Tellez V, Zafar S, Sitharaman B “A novel graphene nanoribbon based platform for highly efficacious nuclear gene delivery” ACS Biomaterials Science & Engineering 2.5 (2016): 798-808.
- Mullick Chowdhury S, Xie S, Fang J, Lee SK, & Sitharaman, B. (2016). “Nanoparticle- Facilitated Membrane Depolarization Induced Receptor Activation: Implications on Cellular Uptake and Drug Delivery”.ACS Biomaterials Science & Engineering 12(2016):2153-2161.
- Mullick Chowdhury S, Wang TY, Bachawal S, Devulapally R, Choe JW, Elkacem, LA& Willmann JK. (2016). “Ultrasound-guided therapeutic modulation of hepatocellular carcinoma using complementary microRNAs”. Journal of Controlled Release, 238, 272- 280.
- Kanakia S, Toussaint J, Kulkarni K, Lee S, Mullick Chowdhury S, Khan S, Shroyer KR, Mallipattu SK, Moore W, Sitahraman B. “Safety and Efficacy of A Novel Graphene-Based Magnetic Resonance Imaging Contrast Agent for Renal Abnormalities” Graphene Technology, 1-12 (2016)
- Abou-Elkacem L, Wilson KE, Johnson S, Mullick Chowdhury S, Bachawal SV, Hackel BJ, Willmann JK “Ultrasound molecular imaging of breast cancer neovasculature using engineered fibronectin scaffold ligands: A novel class of targeted contrast ultrasound agent” Theranostics 2016; 6(11):1740-1752.
- Patel, S. C., Lee, S., Lalwani, G., Suhrland, C., Mullick Chowdhury, S., & Sitharaman, B. (2016). “Graphene-based platforms for cancer therapeutics”. Therapeutic delivery, 7(2), 101-116.
- Mullick Chowdhury, S., Lee T., Sitharaman B (2017) “Ultrasound guided Drug delivery in Cancer” Ultrasonography,36.3,171.
- Lee T, Hyun D, Mullick Chowdhury S, Jakovljevic M, Willmann JK. and Dahl J (2017). “High-resolution passive cavitation mapping by source localization from aperture- domain signals”. Ultrasonics Symposium (IUS), 2017 IEEE International.
- Lee T, Hyun D, Chowdhury SM., Bachawal S, Herickhoff CD, Dahl J. and Willmann JK. (2017). “Image-guided ultrasound/microbubble-mediated drug delivery platform with passive cavitation mapping”. Ultrasonics Symposium (IUS),2017 IEEE International.
- Mullick Chowdhury S, Lee T, Bachawal S, Devulapally R, Elkacem LA& Willmann JK. (2016). Longitudinal Assessment of Ultrasound Guided complementary microRNA therapy of hepatocellular carcinoma. Journal of Controlled Release, 238, 272-280.
- Abou-Elkacem L, Wang H, Mullick Chowdhury S, Kimura R, Bachawal SV, Gambhir SS Tian L, Willmann JK. Thy1 Targeted Microbubbles for Ultrasound Molecular Imaging of Pancreatic Ductal Adenocarcinoma” Clinical Cancer Research, clinicanres-2057, Jan
- Hyun D, Abou-Elkacem L, Perez VA, Mullick Chowdhury S, Willmann JK. and Dahl JJ. (2018). Improved Sensitivity in Ultrasound Molecular Imaging with Coherence-Based Beamforming. IEEE transactions on medical imaging, 37(1), pp.241-250.
- Koraseva A, Abou-Elkacem L, Mullick Chowdhury S, Lindner JR, Kaufmann BA. Seeing the invisible: Ultrasound Molecular Imaging. Ultrasound in Medicine & Biology, 46(3), 2020, 479-497.
- Jain N, Singh S, Singh RK, Khasab T, Shirazi F, Mullick Chowdhury S, Sircar A, Havranek O, Sehgal L, Samaniego F. “Targeting phosphatidylinositol 3-kinase-beta and-delta for Bruton’s Tyrosine Kinase resistance in diffuse large B-Cell Lymphoma” Blood Advances (Accepted).
- Wischussen J, Mullick Chowdhury S, Lee T, Wang H, Bachawal S, Devullapally R, Afjei R, Sukumar UK, Paulmurugan R. Ultrasound-Mediated Delivery of miRNA-122 and anti- miRNA-21 Therapeutically Immunomodulate Murine Hepatocellular Carcinoma In Vivo. Journal of Controlled Release, 321(2020), 272-284
- Sircar A*, Mullick Chowdhury S*, Hart A, Bell WC, Singh S, Sehgal L and Epperla N. “Impact and Intricacies of Bone Marrow Microenvironment in B-cell Lymphomas: From Biology to Therapy. International Journal of Molecular Sciences, 21(3), p.904. 2020 * equal first author
- Mullick Chowdhury S, Abou-Elkacem L, Lee T, Dahl J, Lutz A “Ultrasound and Microbubble Guided Therapeutic Delivery: Underlying mechanisms and Future Outlook” (Accepted, In Press, Journal of Controlled Release, May 2020)
- George B, Mullick Chowdhury S, Hart A, Sircar A, Singh SK, Nath UK, Mamgain M, Singhal NK, Sehgal L, Jain N. “Ibrutinib Resistance Mechanisms and Treatment Strategies for B-Cell Lymphomas” Cancers 2020, 12(5), 1328.
Scott Friedland, MD, PhD PGY-2
I was born and raised in the east suburbs of Cleveland, OH. My first exposure to molecular biology came during my senior year of high school at the Cuyahoga Community College in a biotechnology course. I was fascinated by microarray technology and started dreaming up experiments that I would want to do in the realm of cancer biology. I was drawn to cancer biology after losing multiple family members to cancer, and seeing not only the toll on their health, but the impact on our family while processing their illness and passing.
My first exposure to research outside of the classroom, came at a startup pharmaceutical company called Buckeye Pharmaceutical, where I worked as a laboratory assistant during the Summers of my undergraduate degree at the University of Rochester – where I studied molecular genetics. I helped to investigate potential therapeutic applications for alternating-current interdigitated electrodes. I also learned about various thermochemical techniques for studying the properties of pharmaceuticals. I thoroughly enjoyed the opportunity to develop novel techniques and analyses and expanded my abilities for working independently in a lab setting. I also came to realize that, while I loved research, I needed more of a human and interactive component to my career.
During my junior year of college, I became aware of the existence of MD/PhD programs and decided I would work in a lab and shadow physicians to make sure I had a sense of what I was getting myself into should I enter one. After a year and half of studying the role of an adhesion g protein-coupled receptor (GPR56) in the progression of melanoma in the lab of Dr. Lei Xu, PhD, and shadowing a pediatric oncologist and a radiation oncologist, I had a strong sense that combining the two endeavors of research and medicine would be an ideal career path for me. I wound up staying at the University of Rochester School of Medicine and Dentistry to pursue this path.
During my graduate training I worked under the mentorship of Dr. Aram Hezel, MD, an oncologist and cancer researcher whose lab focuses on the pancreatic cancer and cholangiocarcinoma. I studied the role of ARID1A in the development of each of these cancers. ARID1A, a member of the SWI/SNF chromatin remodeling complex, has multiple cellular functions including aiding in the regulation of chromatin accessibility and thereby altering gene expression. This work has sparked my interest in the interplay between chromatin biology, developmental biology, and process of transformation and progression in cancer.
During medical school, I found myself constantly asking, “Why?” In contrast to some of my classmates who would dutifully memorize the facts necessary to make one’s way through medicine, I always found myself wondering why things worked how they did, and what could be done to improve on what was known. This reaffirmed my desire to combine the two endeavors into the future. While, I had gone into medical school with understanding that oncology would be the most direct application of my research interests, I didn’t want to pigeonhole myself, and waited to make sure that it was the right choice for me before fully committing. During my fourth year of medical school, I finally found that clarity after during an elective on the bone marrow transplant service. I took care of a gentleman receiving CAR-T cell therapy. This overlap between oncology, immunology, and applied genetics floored me, as I could watch in real time as his cancerous lymph node became matted with cytotoxic T-cells and other effectors leading to, last I checked, a durable remission of his otherwise recalcitrant lymphoma.
I continue to have a strong interest in cancer and chromatin biology, and gene regulation. In the lab, I hope to continue to explore the inter-relationship of these processes and potentially find important nodes of regulation that might be leveraged for future treatment. Clinically, I am interested in applying what is known in the realm of cancer biology to try to create individualized therapies for patients who have failed conventional therapy.
In my free time, I enjoy spending time with my cats and friends, rock climbing, fermenting foods, and exploring nature.
- BS, University of Rochester, 2011
- PhD, University of Rochester School of Medicine and Dentistry, 2019
- MD, University of Rochester School of Medicine and Dentistry, 2021
- APSA/ASCI/AAP National Conference Travel Award, ASCI 2019
- URBEST Experience – Cold Spring Harbor Labs Course, UR BEST 2018
- URBEST Experience – Technical Entrepreneurship and Management 2017
- Runner-up Three-Minute Thesis, University of Rochester 2017
- Dean’s Scholarship 2007 – 2011
- GPR56 Inhibits Melanoma Growth by Internalizing and Degrading Its Ligand TG2 Liquan Yang, Scott Friedland, Nancy Corson and Lei Xu Cancer Res February 15 2014 (74) (4) 1022-1031; DOI: 10.1158/0008-5472.CAN-13-1268
- Wang W*, Friedland SC*, Guo B, et al ARID1A, a SWI/SNF subunit, is critical to acinar cell homeostasis and regeneration and is a barrier to transformation and epithelial-mesenchymal transition in the pancreas Gut 2019;68:1245-1258. DOI: http://dx.doi.org/10.1136/gutjnl-2017-315541 * Equal Contribution
Publications in progress
- Bing Guo, Scott C Friedland, William Alexander, et al. Mutations Promote Cholangiocarcinoma through Suppression of TGFβ-Smad4 Signaling Program
Selected Poster Presentations (chronological order)
- Friedland, Scott C., O’Dell, Michael R., Whitney-Miller, Christa L., Hezel, Aram F. Exploring the function of Arid1a and the SWI/SNF Complex in the Developing Pancreas and Pancreatic Cancer. APSA NE Regional Conference, Syracuse NY, 2015. Unpublished conference poster. University of Rochester Medical Center.
- Friedland, Scott C, Wang, Wenjia, O’Dell, Michael R, Whitney-Miller, Christa L, Hezel, Aram F. Arid1a Loss Synergizes with Key Oncogenes to Dysregulate Proliferation and Tissue Homeostasis in the Pancreas. National MD/PhD Student Conference, Keystone, CO, 2016. Unpublished conference poster. University of Rochester Medical Center.
- Friedland, Scott C., Wang, Wenjia, Guo, Bing, O’Dell, Michael R., Whitney-Miller, Christa L., Agostini-Vulaj, Diana, Huber, Aaron R., Getman, Michael R., Steiner, Laurie A., Hezel, Aram F. Exploring the Role of Arid1a in Kras-mediated Transformation (1). University of Rochester Medical Scientist Research Symposium, Rochester, NY, 2017. Unpublished conference poster. University of Rochester Medical Center.
- Friedland, Scott C., Wang, Wenjia, Guo, Bing, O’Dell, Michael R., Whitney-Miller, Christa L., Lillis, Jacquelyn A., Getman, Michael R., Steiner, Laurie A., Hezel, Aram F. Exploring the Role of Arid1a in Kras-mediated Transformation (2). University of Rochester 30th Annual Genetics Day, Rochester, NY 2018. Unpublished conference poster. University of Rochester Medical Center.
- Friedland, Scott C., Wang, Wenjia, Guo, Bing, O’Dell, Michael R., Whitney-Miller, Christa L., Lillis, Jacquelyn A., Getman, Michael R., Steiner, Laurie A., Hezel, Aram F. Exploring the Role of Arid1a in Kras-mediated Transformation (2). 23rd Annual James P. Wilmot Cancer Institute Annual Symposium, Rochester, NY, 2018. Unpublished conference poster. University of Rochester Medical Center.
- Friedland, Scott C., Wang, Wenjia, Guo, Bing, O’Dell, Michael R., Whitney-Miller, Christa L., Lillis, Jacquelyn A., Getman, Michael R., Steiner, Laurie A., Hezel, Aram F. Exploring the Role of Arid1a in Kras-mediated Transformation (2). APSA National Conference, 2018, Chicago, IL. Unpublished conference poster. University of Rochester Medical Center.
- Friedland, Scott C., Wang, Wenjia, Guo, Bing, O’Dell, Michael R., Whitney-Miller, Christa L., Lillis, Jacquelyn A., Getman, Michael R., Steiner, Laurie A., Hezel, Aram F. Exploring the Role of Arid1a in Kras-mediated Transformation (2). Cold Spring Harbor Labs Chromatin and Epigenetics Conference, Cold Spring Harbor, NY, 2018. Unpublished conference poster. University of Rochester Medical Center.
- Friedland, Scott C., Wang, Wenjia, Guo, Bing, O’Dell, Michael R., Whitney-Miller, Christa L., Lillis, Jacquelyn A., Getman, Michael R., Steiner, Laurie A., Hezel, Aram F. Exploring the Role of Arid1a in Kras-mediated Transformation (3). APSA NE Regional Conference, Syracuse NY, 2019. Unpublished conference poster. University of Rochester Medical Center.
- Friedland, Scott C., Wang, Wenjia, Guo, Bing, O’Dell, Michael R., Whitney-Miller, Christa L., Lillis, Jacquelyn A., Getman, Michael R., Steiner, Laurie A., Hezel, Aram F. Exploring the Role of Arid1a in Kras-mediated Transformation (3) APSA National Conference, 2019, Chicago, IL. Unpublished conference poster. University of Rochester Medical Center.
- Scott C. Friedland, “Transcriptomic Vulnerabilities to Screen for Novel Therapeutics for CMV”; Invited talk University of Rochester MSTP Annual Summer Retreat, Rochester, NY, 08/2013.
- Scott C. Friedland, “Exploring the Role of Arid1a in Kras-mediated Transformation”; Invited talk University of Rochester MSTP Medical Scientist Research Symposium, Rochester, NY, 04/2018.
Ankur Sheel, MD, MS, PhD PGY-2
I was born in the United Kingdom and raised in Amherst, Massachusetts. My first research experience came as an undergraduate at the University of Massachusetts, Amherst in the lab of Dr. Lawrence Schwartz studying Programmed Cell Death of the ptilinal muscles in the Tobacco Hawkmoth during pupal development. While using a moth as a model system was unique, I began to dabble in breast cancer research as I elucidated the role of the same process in promoting chemoresistance in Triple Negative Breast Cancers. My experience in the Schwartz lab showed me the personal importance of intellectual curiosity, translational research and how findings in simple model systems can be applied to complex diseases such as cancer. I ultimately completed a dual bachelor’s degree in Biochemistry & Molecular Biology and Neuropsychology at Umass Amherst. I also stayed at UMASS Amherst to complete a one-year thesis based Master’s in Molecular & Cellular Biology which ultimately allowed me to further dive into my research and publish my findings.
As an undergraduate student I had the opportunity to work at the world-famous Guy’s and St. Thomas’s Hospital in London. This experience gave me a glimpse of the potential life of a physician-scientist. I spent half my time on the oncology wards and clinics seeing patients with various malignancies and the other half of my time working on research projects. During my time at Guy’s, I worked on multiple projects involving surgical outcomes in patients with relapsed thymomas, resources available for patients with thymic malignancies, developing High resolution melting assays to detect KRAS and EGFR mutations in patients with Non-Small Cell Lung Cancer (NSCLC) and investigating the role of the KRAS gene in promoting chemoresistance in NSCLC. This experience allowed me to interact with patients with incurable cancer and see the integral role research plays in improving the treatment of these patients and their quality of life. This experience inspired me to ultimately purse a career as a Physician-Scientist.
I joined the Medical Scientist Training Program at the University of Massachusetts Medical school to pursue my MD/PhD. Given my prior work in KRAS and NSCLC I became curious about developing gene editing based therapeutics for NSCLC. Fortunately, my mentor Wen Xue had just joined UMASS as faculty. Having trained with Scott Lowe and Tyler Jacks, the Xue lab focused on developing CRISPR/Cas9 based tools for cancer research and creating CRISPR/Cas9 based therapeutics for NSCLC and HCC. My dissertation involved conducting a CRISPR based screen to identify therapeutic targets in Hepatocellular Carcinoma and then mechanistically validating those targets. I identified TRRAP, a 480kd pseudokinase, as a potential therapeutic target in HCC. CRISPR based knockdown of TRRAP resulted in G2-M senescence and inhibited tumor growth in both in-vivo and in-vitro models. Ultimately, TRRAP knockdown resulted in macrophage mediated clearance of tumor cells in vivo and thus promoting tumor regression in-vivo. I also worked on various other projects in which I developed CRISPR based tools to rapidly generate tumor models in vivo and in which I utilized CRISPR based techniques to study single protein dynamics during oncogenic transformation in-vitro. Participating in these projects exposed me to the world of experimental therapeutics in cancer research for the first time. Being at UMASS Medical school I was fortunate enough to be in an environment where RNA research was robust. I had the privilege of working with Victor Ambros, the Lasker award winner for the discovery of microRNAs. Under both Dr. Xue and Dr. Ambros’s guidance I successfully applied for an NIH F30 Ruth L. Kirschstein National Research Service Award (NRSA) to investigate the role of miR-34a in relapse of NSCLC after EGFR and KRAS inhibition.
When I returned to medical school for my clinical years I quickly gravitated to Internal Medicine and Oncology as my career choice. While applying for residency programs I was looking for a program that could help me develop into a well-rounded internist comfortable with medical management of acute and chronic conditions, as well as allow me to see rare, exotic case presentations while also promoting research. During my interview at OSU I quickly realized that OSU not only embodied this ideology in their training but the mentors at OSU and at the James were extremely approachable and willing to train mentees. This, combined with the commitment to mentorship and innovative approaches to career development, the excellent clinical training, and the amazing resources available through The James and the Comprehensive Cancer Center made Ohio State’s PSTP a clear choice for me.
- MD, Medical Scientist Training Program, The University of Massachusetts Medical School, 2021
- PhD, Medical Scientist Training Program, RNA Therapeutics Institute, The University of Massachusetts Medical School, 2021
- MS, Molecular and Cellular Biology, University of Massachusetts, 2014
- BS, Biochemistry & Molecular Biology, University of Massachusetts, Magna Cum Laude, 2013
- BS, Psychology (Neuroscience), University of Massachusetts, Magna Cum Laude, 2013
- NIH/NCI Ruth L. Kirschstein National Research Service F30 Award (F30CA232657) awarded on first application (5th Percentile), July 2018-July 2021
- Session Chair, 2018 RNA Therapeutics Symposium, University of Massachusetts Medical School.
- UMASS Medical School, NIH MSTP Fellowship Recipient, 2015-2017
- UMASS Amherst 21st Century Leaders Award Recipient, 2013
- UMASS Amherst Rising Researcher Award Recipient, 2013
- UMASS Amherst Junior Fellow in Life Sciences, 2012
- Harris, T.*, Sheel, A.*, Zong, Y.*, Hutchinson, L. M., Cornejo, K. M., Bubendorf, L., Yates, J. & Fischer, A. H. (2021). Cytologically targeted next-generation sequencing: a synergy for diagnosing urothelial carcinoma. Journal of the American Society of Cytopathology, 10(1), 94-102.
- Sheel, A.*, Shao, R.*, Brown, C.*, Johnson, J., Hamilton, A., Sun, D., Oppenheimer, J., Smith, W., Visconti, P.E., Markstein, M. Bigelow, C. & Schwartz, L.M. (2020). Acheron/larp6 is a Survival Protein that Protects Skeletal Muscle from Programmed Cell Death During Development. Frontiers in Cell and Developmental Biology, 8, 622.
- Elaimy, A. L., Wang, M., Sheel, A., Brown, C. W., Walker, M. R., Amante, J. J., Xue, W., Chan, A., Baer, C.,Goel, H., & Mercurio, A. M. (2019). Real-time imaging of integrin β4 dynamics using a reporter cell line generated by Crispr/Cas9 genome editing. Journal of Cell Science, jcs-231241. Kwan, S. Y*., Sheel, A.*, Song, C. Q., Zhang, X. O., Jiang, T., Dang, H., & Weng, Z. (2019). Depletion of TRRAP Induces p53-Independent Senescence in Liver Cancer by Down-Regulating Mitotic Genes. Hepatology, 71(1), 275-290.
- Sheel, A., Kwan, S., & Xue, W. (2019). Integrating CRISPR screening with tumor genomic analyses to identify therapeutic targets in hepatocellular carcinomas (HCC) independent of P53. American Society of Clinical Oncology, e14659-e14659.
- Mou, H.*, Ozata, D.M.*, Smith, J.L.*, Sheel, A., Kwan, S.Y., Hough, S., Kucukural, A., Kennedy, Z., Cao, Y.& Xue, W. (2019). CRISPR-SONIC: targeted somatic oncogene knock-in enables rapid in vivo cancer modeling. Genome Medicine, 11:21.
- Banna, G. L., Sheel, A., Sheel, V., Bille, A., Routledge, T., Fernando, S., Nair, A., & Lal, R. (2017). Treatmentand prognostic factors of patients with thymic epithelial tumors at first recurrence or progression. Future Oncology, 13(27), 2429-2439.
- Mou, H., Smith, J. L., Peng, L., Yin, H., Moore, J., Zhang, X. O., Song, C.Q., Sheel, A., Wu, Q., Ozata, D.M., Li, Y., Anderson, D.G., Emerson, C.P., Sontheimer, E.J., Moore., M.J., Weng, Z., & Xue, W. (2017). CRISPR/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion. Genome Biology, 18(1), 108.
- Sheel, A., & Xue, W. (2016). Genomic amplifications cause false positives in CRISPR screens. Cancer Discovery, 6(8), 824-826.
Youssef Youssef, MD PGY-2
I grew up in a small village called Oyoun El Wadi (Eyes of the Valley), located two hours north of Damascus in Syria. Through a small mountain pass in my village, there is a big stone inscribed with three words "SCIENCE-ETHICS-WORK". It was there that a village elder told me about a scientist he knew who devoted his entire life to understand the function of cells. This scientist’s work interests and life has become my professional guide.
After obtaining my Medical Degree from the University Damascus, Syria, in 2011. I moved to Columbus and joined the Comprehensive Cancer Center at the Ohio State University (OSU) in 2014 as a visiting scholar where I worked in Michael Caligiuri’s lab under the direct mentorship of Dr. Aharon Freud for two years. In Dr. Freud’s lab, I investigated C-type lectin-like surface activating receptor (NKp80), CD200R1 and killer immunoglobulin like receptor (KIR) expression patterns during later stages of NK cell development as these receptors are key determinants in NK cell anti-tumor activity and in NK cell graft-versus-leukemia effect in the post-transplant setting. I also investigated EBV-driven Extranodal NK/T-cell lymphoma (ENKTL) and its cell of origin based on the normal NK cell development framework. For these projects, I mastered multi-parametric flow cytometry and cell sorting techniques which I used to characterize NK cell maturation patterns and quantify KIR and NKp80 acquisition. Our work was published on Cell Report and Immunity in 2016-2018.
Later on, I completed three years of Clinical and Anatomical Pathology training up till 2018 at the Ohio State University. All these experiences allowed me to master critical laboratory techniques in cellular and molecular biology as well as cellular immunology. While I found this experience in basic immunology and pathology to be exciting and rewarding, I quickly realized that my true passion involves preclinical and clinical development of novel treatment strategies for hematologic malignancies and decided to continue my research effort in a translational laboratory where I could focus on the identification of novel therapeutic targets and drug development for aggressive B-cell Non-Hodgkin lymphomas.
During my post-doctoral fellowship, I worked on the characterization of the oncogenic role of transducine β-like 1 (TBL1) in aggressive B-cell lymphomas. TBL1 is a scaffold protein that promotes cell survival and proliferation by recruiting β-catenin to the promoter of Wnt target genes (MYC, BIRC5, and CCND1). My data showed that TBL1 is over-expressed and essential for DLBCL lymphoma cell survival. Tegavivint (first-in-class small molecule inhibitor of TBL1/currently in a phase-I clinical trial for desmoid tumors) leads to lymphoma cell death in vitro and in vivo. More importantly, we were the first to identify a novel, β-catenin-independent, pathway in which TBL1 regulates the stability of c-Myc rather than the transcription. This novel pathway is regulated by TBL1 interaction with the SCF complex a complex which controls the stability of many critical cellular proteins. We found PLK1 to be one of those downregulated protein upon TBL1 inhibition. PLK1 is key regulator of c-Myc stability. This TBL1-PLK1-Myc identified novel circuit is critical for lymphoma cell survival in general and Myc addicted lymphoma in particular (Double Hit and Triple Hit lymphomas). My current research line is extremely valuable, and has important clinical implications as it provides the scientific rationale and framework to translate into clinic tegavivint especial in aggressive NHL in general and Myc-driven subsets in particular. This work was awarded by Pelotonia fellowship grant with the highest score at OSU and was recently published (9/2020) in Haematologica.
My long-term career goal is to become a well-trained hematologist and to eventually lead a translational research laboratory as an independent investigator in the field of hematological malignancies aiming to dissect their molecular mechanisms with the final goal of finding novel therapeutic approaches and lead innovative clinical trials. I strongly believe that the Physician Scientist Training Program at the Ohio State University is the right place where I would be supported by a great mentorship team and be provided with the right exposure to research and clinical hematology to continue developing the required skills to become an excellent physician scientist.
In my free time I like to travel, exercise and buy new shoes.
Education and training
- MD, Damascus University School of Medicine, 2006 - 2012.
- Post-doctoral fellowship, The Ohio State University, 2014 – 2016.
- Anatomical and Clinical Pathology, The Ohio State University, 2016 – 2019.
- Post-doctoral fellowship, The Ohio State University, 2019 – 2021.
Awards and Honors
- Selected Oral Presentation at Collage of American Pathologists 2017 Annual Meeting: Clinical, histological and cytological features in noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and follicular variant of papillary thyroid carcinoma (FVPTC) (CAP. 2017 Oct 8).
- Von Haam award for pathology resident academic productivity, second place (The Ohio State University. 2018 Jun 14).
- Selected Poster as a 2019 Annual Scientific Meeting Abstract Finalist, 20th Annual OSUCCC – James Scientific Meeting. Targeting transducin β-like protein 1 in diffuse large B-cell lymphomas (The Ohio State University. 2019 May 7).
- Pelotonia fellowship grant with highest score at OSU; 100k (04/2019-04/2021), Targeting TBL1 in Diffuse large B cell lymphoma.
- National Interest Waiver-EB2 status, granted by US Citizenship and Immigration Services (USCIS), Dallas, Texas. ‘‘granted to those who have exceptional ability and whose employment in the US would greatly benefit the nation’’. (uscis.gov) (2020 Apr 24).
- Selected Poster at the Ohio State University Pathology Retreat research day, second place in the experimental category. CD200R downregulation identifies a population of intermediate natural killer cells showing a mature epigenetic profile and capable of KIR acquisition (The Ohio State University. 2020 Nov 4).
- ASH achievement Award, CD200R downregulation identifies a population of intermediate natural killer cells showing a mature epigenetic profile and capable of KIR acquisition (ASH 2021).
- Freud, A.G., Keller, K.A., Scoville, S.D., Mundy-Bosse, B.L., Cheng, S., Youssef, Y., Hughes, T., Zhang, X., Mo, X., Porcu, P. and Baiocchi, R.A., 2016. NKp80 defines a critical step during human natural killer cell development. Cell reports, 16(2), pp.379-391.
- Victor, A.R., Nalin, A.P., Dong, W., McClory, S., Wei, M., Mao, C., Kladney, R.D., Youssef, Y., Chan, W.K., Briercheck, E.L. and Hughes, T., 2017. IL-18 drives ILC3 proliferation and promotes IL-22 production via NF-κB. The Journal of Immunology, 199(7), pp.2333-2342.
- Youssef, Y., Shen, R., Tonkovich, D. and Li, Z., 2018. Clinical features, onsite evaluation, and follow-up results in patients with suspicious for adenocarcinoma on EUS-guided FNA of pancreas. Journal of the American Society of Cytopathology, 7(4), pp.212-218.
- Chan, W.K., Kang, S., Youssef, Y., Glankler, E.N., Barrett, E.R., Carter, A.M., Ahmed, E.H., Prasad, A., Chen, L., Zhang, J. and Benson, D.M., 2018. A CS1-NKG2D bispecific antibody collectively activates cytolytic immune cells against multiple myeloma. Cancer immunology research, 6(7), pp.776-787.
- Mundy-Bosse, B., Denlinger, N., McLaughlin, E., Chakravarti, N., Hwang, S., Chen, L., Mao, H.C., Kline, D., Youssef, Y., Kohnken, R. and Lee, D.A., 2018. Highly cytotoxic natural killer cells are associated with poor prognosis in patients with cutaneous T-cell lymphoma. Blood advances, 2(15), pp.1818-1827.
- Chen, L., Youssef, Y., Robinson, C., Ernst, G.F., Carson, M.Y., Young, K.A., Scoville, S.D., Zhang, X., Harris, R., Sekhri, P. and Mansour, A.G., 2018. CD56 expression marks human group 2 innate lymphoid cell divergence from a shared NK cell and group 3 innate lymphoid cell developmental pathway. Immunity, 49(3), pp.464-476.
- Harrington, B.K., Wheeler, E., Hornbuckle, K., Shana’ah, A.Y., Youssef, Y., Smith, L., Hassan II, Q., Klamer, B., Zhang, X., Long, M. and Baiocchi, R.A., 2019. Modulation of immune checkpoint molecule expression in mantle cell lymphoma. Leukemia & lymphoma.
- Xiao, R., Mansour, A.G., Huang, W., Chrislip, L.A., Wilkins, R.K., Queen, N.J., Youssef, Y., Mao, H.C., Caligiuri, M.A. and Cao, L., 2019. Adipocytes: a novel target for IL-15/IL-15Rα cancer gene therapy. Molecular Therapy, 27(5), pp.922-932.
- Youssef, Y., Karkhanis, V., Chan, W.K., Jeney, F., Canella, A., Zhang, X., Sloan, S., Prouty, A., Helmig-Mason, J., Tsyba, L. and Hanel, W., 2021. Transducin b-like protein 1 controls multiple oncogenic networks in diffuse large B-cell lymphoma. haematologica, 106(11), p.2927.
- Nalin, A.P., Kowalski, J.J., Sprague, A.C., Schumacher, B.K., Gerhardt, A.G., Youssef, Y., Vedantam, K.V., Zhang, X., Siebel, C.W., Mace, E.M. and Caligiuri, M.A., 2020. Notch regulates innate lymphoid cell plasticity during human NK cell development. The Journal of Immunology, 205(10), pp.2679-2693.
- Sloan, S.L., Renaldo, K.A., Long, M., Chung, J.H., Courtney, L.E., Shilo, K., Youssef, Y., Schlotter, S., Brown, F., Klamer, B.G. and Zhang, X., 2021. Validation of protein arginine methyltransferase 5 (PRMT5) as a candidate therapeutic target in the spontaneous canine model of non-Hodgkin lymphoma. PloS one, 16(5), p.e0250839. (PLOS ONE. 2021 May 06).
- Jatiani, S.S., Christie, S., Leshchenko, V.V., Jain, R., Kapoor, A., Bisignano, P., Lee, C., Kaniskan, H.Ü., Edwards, D., Meng, F. and Laganà, A., 2021. SOX11 inhibitors are cytotoxic in mantle cell lymphoma. Clinical Cancer Research, 27(16), pp.4652-4663.
- Zhang, P., Brinton, L.T., Williams, K., Sher, S., Orwick, S., Tzung-Huei, L., Mims, A.S., Coss, C.C., Kulp, S.K., Youssef, Y. and Chan, W.K., 2021. Targeting DNA damage repair functions of two histone deacetylases, HDAC8 and SIRT6, sensitizes acute myeloid leukemia to NAMPT inhibition. Clinical Cancer Research, 27(8), pp.2352-2366.
Publication in progress
- Walter Hanel, Pushba Lata, Youssef Youssef, Liudmyla Tsyba, Dennis Huszar, Alex Prouty, Xiaoli Zhang, JoBeth Helmig-Mason, Bethany L Mundy-Bosse, Samir Parekh, Kami J Maddocks, Robert A Baiocchi, Lapo Alinari. Sumoylation is a therapeutic vulnerability in Mantle cell lymphoma. (Submitted 2021 Nov, The Journal of Clinical Cancer Research).
- Bethany Mundy-Bosse, Christoph Weigel, Yue-Zhong Wu, Salma Abdelbaky, Youssef Youssef, Susana Beceiro Casas, Nicholas Polley, Gabrielle Ernst, Karen Young, Kathleen McConnell, Ansel Nalin, Aharon Freud, and Christopher Oakes. Identification and targeting of the developmental blockade in extranodal natural killer/T cell lymphoma. (Submitted 2021 Nov, Blood Cancer Discovery).
- Youssef Youssef*, Ansel P. Nalin*, Jesse J. Kowalski, Matthew R. Lordo, Adam G. Gerhardt, Anthony G. Mansour, David Clever, Amir Horowitz, Bethany L. Mundy-Bosse, James S. Blachly, Bradley W. Blaser, Christopher C. Oakes, Aharon G. Freud. CD200R downregulation identifies a population of intermediate natural killer cells showing a mature epigenetic profile and capable of KIR acquisition.
- Youssef Youssef, Gru AA, Freud AG. NK-cell Leukemias/Lymphomas. In Gru AA, Schaffer, A. Wolters Kluwer Health, Lippincott Williams & Wilkins. (Ed.), Hematopathology of the Skin: Clinical & Pathological Approach. (pp. 11). Columbus: Gru AA (Published 2016).
- Youssef Youssef, Clinical, histological and cytological features in noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and follicular variant of papillary thyroid carcinoma (FVPTC) (CAP. 2017 Oct 8).
- Youssef Youssef, NK cell metabolic signature, Hematopathology department, Stanford University, CA (Hematopathology grand round. 2018 Feb 1).
Kurt Host, MD, PhD PGY-3
I was born and raised in Zoar, OH. Early illnesses in the family sparked an interest in both the how and why of diseases and, in particular, microbiology. Following high school, I enrolled at the Ohio State University with a major in microbiology. With a naive interest in the field and a want to explore the true work of microbiology, I applied for a wide range of lab positions. I was fortunate to land in the laboratory of Dan Wozniak. My work in the lab focused on a key phenotypic shift during the transition from acute to chronic Pseudomonas aeruginosa infections in Cystic Fibrosis patients. This work lead to a multitude of undergraduate presentations and a co-authorship. More importantly it opened my eyes to the possibility of research for my long term career. After having entered undergraduate with a vague thought of medical school, I found myself now gravitating towards both medicine and science.
To pursue both medicine and science, I enrolled in the University of North Carolina’s MD/PhD program in Chapel Hill, NC. During my early years in medical school, I remained interested in infectious diseases but found myself more and more interested in oncology. Again, I was fortunate to find a fantastic mentor who could span both subjects; Blossom Damania. My dissertation work focused on the interaction of Kaposi’s sarcoma associated herpesvirus (KSHV), an oncogenic virus, with the host immune system. In particular, we explored the effect of KSHV on immune checkpoint regulation. We were the first group to show that KSHV induces immune checkpoint inhibitor (Programmed Death Ligand 1 [PD-L1]) expression in monocytes, highlighting a potential target for treatment in KSHV associated malignancies and uncovering an additional avenue of immune modulation for KSHV. Upon finishing my graduate work and returning to medical school, my interest clinically ranged widely but my niche was clearly internal medicine.
As I transitioned to residency, Ohio State quickly differentiated itself as a special place to train. It offered both outstanding clinical training and clear research support in a highly collaborative environment. The resources, infrastructure, cutting edge work, and, most importantly, the people here set OSU apart. The Physician Scientist Training Program has been exceptionally welcoming and supportive of finding the right fit for my long term goals. Finally, Columbus is a lovely place to call home with a great food scene, lots of breweries, beautiful parks, and a very affordable cost of living.
My research interests remain in oncogenic viruses. Specifically in the epigenetic regulation of viral oncogenesis, virus-host immune interactions, and exploration of further malignant treatment modalities. I aim to continue working on KSHV and its associated malignancies but remain excited to branch out as the opportunities arise.
In my free time I enjoy brewing beer, cooking new recipes, and spending time with my wife and dogs.
Sahkalp Malhotra, MD, PhD PGY-3
I was born in New Delhi, India but was only two years old when my family moved abroad. After spending seven years in Papua New Guinea and a few months in Darwin, Australia, we immigrated to the United States and finally settled in the suburbs of Chicago in 1998. I graduated from Downers Grove South High School in 2007, hoping to pursue a future in medicine.
However, I did not realize my passion for research until I began my undergraduate studies at Miami University (Oxford, OH). As a microbiology major, I joined Dr. Joseph Carlin’s laboratory, wherein my project focused on IFN-gamma-mediated responses to Chlamydia infections. Under Dr. Carlin’s tutelage, I learned the foundational tenets of biomedical research: how to develop hypotheses, design and perform experiments, and communicate my findings. These formative experiences led to two summer research internships- one at a pharmaceutical company in Beaverton, Oregon, and another at Loyola University in Chicago. During both internships, I had the opportunity to explore how bacterial and viral pathogens circumvent the innate immune response, further solidifying a primary research interest in the host-microbial interface.
After completing my undergraduate studies, I joined the Ohio State University’s Medical Scientist Training Program (MSTP). I had the privilege of doing my graduate research in Dr. Daniel Wozniak’s laboratory, where I studied chronic pulmonary infections caused by Pseudomonas aeruginosa in cystic fibrosis (CF). Specifically, I focused on mechanisms of innate immune evasion by P. aeruginosa mucoid variants, aggressive mutants that arise during chronic colonization of the CF lung. I was fortunate that this work resulted in a pre-doctoral TL1 fellowship from the Center for Clinical and Translational Sciences, multiple presentations at national and internal conferences, as well as publications. Most importantly, given the genuine support of all my mentors and the extraordinary research and clinical training I had received at OSU, I decided to stay here for my internal medicine residency.
During my PGY-1 year, I joined the Physician Scientist Training Program (PSTP). The innovative vision of the program leadership, well-conceived but flexible pathways of research integration with clinical training, and the chance to seek ongoing guidance from a personalized research committee were some of the key features that drew me to our PSTP. Furthermore, as OSU continues to grow, opportunities for trainees in all sectors of clinical and research interests are truly limitless.
I remain interested in the pathophysiology of chronic infection/inflammation of the lungs and hope to pursue a fellowship in Pulmonary/Critical Care Medicine. In my free time, I enjoy sampling all of Columbus’s incredible restaurants and playing tennis and racquetball.
- BA, Miami University- 2011
- PhD, The Ohio State University- 2018
- MD, The Ohio State University- 2020
- Malhotra, S., Hayes, D. Jr., Wozniak, D.J. (2019) Mucoid Pseudomonas aeruginosa and regional inflammation in the cystic fibrosis lung. Journal of Cystic Fibrosis. 18 (6): 796-803. https://doi.org/10.1016/j.jcf.2019.04.009
- Malhotra, S., Hayes, D. Jr., Wozniak, D.J. (2019) Cystic fibrosis and Pseudomonas aeruginosa: The Host-Microbial Interface. Clinical Microbiology Reviews. 32:e00138-18. https://doi.org/10.1128/CMR.00138-18.
- Malhotra, S., Limoli, D.H., English, A.E., Parsek, M.R., Wozniak, D.J. (2018) Mixed communities of mucoid and nonmucoid Pseudomonas aeruginosa exhibit enhanced resistance to host antimicrobials. mBio. 9:e00275-18. https://doi.org/10.1128/mBio.00275-18.
- Brockson, M.E., Novotny, L.A., Mokrzan, E.M., Malhotra, S., Jurcisek, J.A., Akbar, R., Devaraj, A., Goodman, S.D., and Bakaletz, L.O. (2014) Evaluation of the kinetics and mechanism of action of anti-integration host factor mediated disruption of bacterial biofilms. Molecular Microbiology. 93(6): 1246-1258. https://doi.org/10.1111/mmi.12735 A
- bdulrahman, B.A., Abu Khweek, A., Akhter, A., Caution, K., Tazi, M., Hassan, H., Zhang, Y., Rowland, P.D., Malhotra, S., Aeffner, F., Davis, I.C., Valvano, M.A., and Amer, A.O. (2013) Depletion of the ubiquitin binding adaptor molecule SQSTM1/p62 from macrophages harboring CFTR ΔF508 mutation improves the delivery of Burkholderia cenocepacia to the autophagic machinery. The Journal of Biological Chemistry. 288: 2049-2058. https://doi.org/10.1074/jbc.M112.411728
- Malhotra, S. Yang, C. Hayes, D. Jr., Wozniak, D.J. Regional infection and inflammation in cystic fibrosis: A pilot study with lung explants and a novel histopathology grading system. Poster presentation: CHEST Annual Meeting; 2020 Oct 17-21; Virtual conference due to COVID-19
- Malhotra, S. and Prosek, J. Successful management of chronic ifosfamide nephrotoxicity with immunosuppression: A case series. Poster presentation: American Society of Nephrology- Kidney Week; 2020 Oct 22-25; Virtual conference due to COVID-19
- Malhotra, S., Cerne, J., Chen, D.T., Hing, Z.A., LaRocco, A.M., Saldivar, L.E., Scheetz, S.D., Besecker, B. Implementing a checklist to improve non-invasive ventilation decision-making in an ICU step-down unit. Poster presentation: OSU College of Medicine QI Symposium; 2020 Apr; Virtual event due to COVID-19.
- Malhotra, S., Wozniak, D.J., Hayes, D, Jr. Mucoid Pseudomonas aeruginosa infection is associated with regional inflammation in the cystic fibrosis lung. Oral presentation: ACTS Annual Meeting: Translational Science; 2018 Apr 18-21; Washington, D.C.
- Malhotra, S., Limoli, D.H., English, A., Wozniak, D.J. Mixed communities of mucoid and non-mucoid Pseudomonas aeruginosa exhibit enhanced resistance to host antimicrobials. Poster presentation: 16th International Conference on Pseudomonas; 2017 Sep 5-9; Liverpool, United Kingdom.
- Malhotra, S., Limoli, D.H., English, A., Wozniak, D.J. Mixed communities of mucoid and non-mucoid Pseudomonas aeruginosa exhibit enhanced resistance to host antimicrobials. Oral presentation: Pediatric Medical Student Research Forum; 2017 Sep 1-2; Orlando, FL.
- Malhotra, S., Limoli, D.H., English, A., Wozniak, D.J. Mixed communities of mucoid and non-mucoid Pseudomonas aeruginosa exhibit enhanced resistance to host antimicrobials. Poster presentation: ACTS Annual Meeting: Translational Science; 2017 Apr 19-21; Washington, D.C.
- Malhotra, S., Limoli, D.H., Wozniak, D.J. Mucoid and non-mucoid isolates of Pseudomonas aeruginosa exhibit enhanced resistance to host antimicrobials in mixed communities. Oral presentation: Hayes Graduate Research Forum; 2017 Mar 3; Columbus, OH.
- Malhotra, S., Limoli, D.H., English, A., Wozniak, D.J. Mixed communities of mucoid and non-mucoid Pseudomonas aeruginosa exhibit enhanced resistance to host antimicrobials. Oral presentation: Mid-Atlantic Microbial Pathogenesis Meeting; 2017 Feb 12-14; Wintergreen, VA.
- Malhotra, S., Limoli, D.H., Wozniak, D.J. Mucoid conversion affords Pseudomonas aeruginosa differential protection from neutrophil-derived antimicrobials. Oral presentation: Medical Scientist Training Program Faculty Forum; 2016 Jan 21; Columbus, OH.
- Malhotra, S., Novotny, L.A., Goodman S.D., Bakaletz L.O. Fine mapping the functional epitopes within Integration Host Factor, a novel therapeutic target for nontypeable Haemophilus influenzae- induced diseases of the respiratory tract. Poster presentation: AMA Research Symposium; 2014 Nov 7; Dallas, TX.
- Malhotra S., Novotny L.A., Goodman S.D., Bakaletz L.O. Identification of immunoprotective domains within the bacterial DNA-binding protein, Integration Host Factor. Oral presentation: Nationwide Children’s Hospital ID Consortium Symposium.; 2013 Nov 21; Columbus, OH.
- Malhotra S., Novotny L.A., Goodman S.D., Bakaletz L.O. Identification of immunoprotective domains within the bacterial DNA-binding protein, Integration Host Factor. Oral presentation: 7th Extraordinary International Symposium on Recent Advances in Otitis Media; 2013 Jun 12-16; Stockholm, Sweden.
- Malhotra S., Novotny L.A., Goodman S.D., Bakaletz L.O. Identification of immunoprotective domains within the DNA-binding protein, Integration Host Factor. Oral presentation: Biomedical Sciences Graduate Program Annual Retreat; 2012 Dec 5; Columbus, OH.
- Quality Improvement Capstone Project Award- Top group, Poster presentation, OSU College of Medicine (2020)
- OSUWMC Research Day Award- Top 2 Poster presentation, MSTP Student Category (2018)
- Burroughs Wellcome Fund Trainee Travel Award- Top Abstracts, Oral presentation at the ACTS Annual Meeting, Washington, D.C. (2018)
- TL1 Pre-Doctoral Fellowship- Center for Clinical and Translational Science (CCTS), The Ohio State University College of Medicine; Grant number: TL1TR001069 (2016-2018)
- Pediatric Medical Student Research Forum Award- Third Place, Oral presentation (2017)
- Department of MI&I Travel Award- For oral presentation at the Pediatric Medical Student Research Forum, Orlando, FL (2017)
- Hayes Graduate Forum Award- First Place, Oral presentation, Professional Biological Sciences Section (2017)
- MAMPM Trainee Travel Award- For oral presentation at the Mid-Atlantic Microbial Pathogenesis Meeting, Wintergreen, VA (2017)
- The Ohio State University College of Medicine Travel Grant- For poster presentation at the AMA Research Symposium, Dallas, TX (2014)
- Center for Microbial Interface Biology (CMIB) Symposium Travel Award- First Place, Poster presentation, Graduate Student Category (2014)
- ID Consortium Symposium Award- Top 2 Oral presentation (2013)
- Biomedical Sciences Graduate Program Annual Retreat Award- First Place, Oral presentation, and Proctor & Gamble recognition-of-excellence award (2012)
- Patient Centered Research Ethics Scholarship- Second Place: Essay entitled “Advocating the inclusion of pregnant women in clinical trials" (2012)
- MSTP Leadership and Academic Achievement Scholarship (2011)
- Harrison Scholarship- Full tuition scholarship at Miami University (2007-2011)
Melissa Babcook, MD, PhD PGY-4
I was born in Lincoln, NE and raised in the Midwest. As a non-traditional student, I had a career as an analytical chemist, college instructor, and Water Utilities Director for a multi-county potable water production and distribution system in Northwest Ohio prior to returning to graduate and medical school. Unbeknownst to me at the time, these experiences were instrumental in my development as a clinician-scientist-educator and gave me the maturity, grit, crisis management, leadership, and communication skills necessary for such a position, a passion for teaching and mentorship, and a unique perspective and ability to incorporate analytical chemistry techniques into biomedical research.
A significant family history of pancreatic cancer initially inspired my decision to pursue cancer research, medicine, and a career as a physician-scientist-educator in hematology-medical oncology. I completed a Ph.D. from Case Western Reserve University under the mentorship of Sanjay Gupta PhD and subsequently secured postdoctoral appointments at University Hospitals Case Medical Center/Seidman Cancer Center and the NIH National Cancer Institute in Bethesda, MD.
My graduate work initially started with high-throughput screening of ~100 FDA-approved drugs alone and in combination for potential repurposing as prostate cancer chemotherapy; through this screening, we identified combination simvastatin and metformin as a novel potential chemotherapeutic option for metastatic castration-resistant prostate cancer (CRPC). Using metastatic CRPC cell lines, which were resistant to taxane chemotherapy, we discovered that combination simvastatin and metformin synergistically and significantly inhibited viability and metastatic properties of invasion, migration, adhesion-independent growth with minimal adverse effects on normal prostate epithelial cell viability. Combination simvastatin and metformin did this by modulating key metabolic aberrations found in metastatic CRPC, leading to decreased Akt phosphorylation and AMPKα Ser-486/491 inhibitory phosphorylation, increased AMPKα activity, decreased HMGCR activity, and reduced total cellular cholesterol and its synthesis in both cell lines. Oral treatment with combination simvastatin and metformin at pharmacologically-relevant dosages also inhibited primary tumor growth and prevented bone metastasis in an orthotopic mouse model of metastatic CRPC, and did so more effectively and with significantly less toxicity than docetaxel. We also demonstrated that simvastatin and metformin combination chemotherapy may further translate as a therapy for bone metastatic triple-negative breast cancer, as these cells possess similar metabolic alterations. Further, we determined that combination simvastatin and metformin treatment led to Ripk1- and Ripk3-dependent necroptosis, as determined by propidium iodide-Annexin V flow cytometry, increase in Ripk1 and Ripk3 protein expression, necrosome formation, HMGB-1 extracellular release, and rescue from necroptosis with necrostatin-1 and Ripk3-targeting siRNA. This research demonstrated that simvastatin and metformin have potential as effective treatment for chemotherapy-resistant metastatic CRPC cells.
As a postdoctoral fellow at CWRU under the mentorship of Sanjay Gupta PhD, Gregory MacLennan MD, and Robert Abouassaly MD, I designed, obtained funding for, and completed a retrospective, case-control, single-institution pilot study in which we discovered a significant and novel association between AMPKα Ser-486/491 phosphorylation and progression to castration-resistance and metastasis in prostate cancer. In this study, we also showed that increased AMPKα protein expression, decreased AMPKα activity, and loss of nuclear AMPKα and p-AMPKα are associated with prostate cancer progression to metastasis. In a separate postdoctoral project, I extracted and analyzed specimens via 1H-NMR and performed principal component analysis of spectral data for a metabolomic project aiming to identify plasma and prostate tissue biomarkers of apigenin and green tea polyphenol treatment response and non-response in the transgenic adenocarcinoma of the mouse prostate model. I have maintained a solid collaborative partnership with my former research mentor, Sanjay Gupta PhD, and have continued to publish work with him throughout medical school.
During graduate school and postdoctoral fellowship, I was given the opportunity to mentor several high school students through the CWRU High School Student Scientific Enrichment and Opportunity Program and undergraduate students in their Senior Capstone research projects. I helped these students learn basic laboratory and cell culture techniques and designed and supervised their independent projects, which culminated in poster presentations and published articles. One of my mentees, Christine Oak, won an award for her poster presentation at the CWRU annual Research ShowCASE. Three of my former mentees are pursuing careers in medicine and science; one is currently a third-year medical student at St. Louis University School of Medicine, one is a student at Kent State University School of Podiatric Medicine, and one is a Lab Technician for Sherwin-Williams. I plan to continue teaching, mentoring, and inspiring a love of medicine and research through the Physician Scientist Training Program outreach and in my future career.
As a postdoctoral fellow at the NIH National Cancer Institute in Bethesda, MD in the laboratory of David VanderWeele MD PhD, I assisted my advisor in initiating 3-D spheroid prostate cancer cell culture, planned and purchased materials for start-up of his nu/nu mouse colony, and developed and taught mouse surgeries integral to the project to my advisor and other postdoctoral fellows in the laboratory. While in Bethesda, I also had the opportunity to clerk in Medical Oncology at the NIH Clinical Center with my advisor and learn how he integrated and balanced clinical practice and translational research laboratory.
While attending the University of Toledo College of Medicine, I was able to clerk in adult Hematology-Medical Oncology at both the UTMC Dana Cancer Center and Toledo Clinic Cancer Center, and in Psycho-oncology and on the bone marrow transplant unit at Duke University Cancer Center and Tulane University Medical Center during visiting medical student rotations, diversifying my experience in Hematology-Medical Oncology. I established a new collaboration with Kristi Skeel-Williams MD and branched into psych-oncology research to investigate the psychosocial aspects of surgical treatment decisions of women with ductal carcinoma in situ.
I chose the Ohio State University Physician Scientist Training Program because of its established track record of mentoring trainees into funded, competent physician-scientists. Between my clinic at the Martha Morehouse Medical Plaza and the large catchment of the Wexner Medical Center as a tertiary care center, I felt OSU would allow me to develop into a well-rounded internist comfortable with medical management of acute and chronic conditions, as well as allow me to see rare, exotic case presentations. The James Cancer Center is the perfect environment for collaboration, as surgical oncology, radiation oncology, hematology and medical oncology are all under same umbrella, and it was important to me that my training included exposure to bone marrow transplant. The Division of Hematology and Oncology has a large faculty body, including several clinician-scientists pursuing translational and clinical research in prostate and breast cancer, drug development, and cancer genetics. I look forward to beginning the program in June!
August 2015–May 2019, Doctor of Medicine; University of Toledo College of Medicine
July 2009–January 2015, Doctor of Philosophy in Nutrition; Case Western Reserve University
August 1999–May 2004, Bachelor of Science, Dual Degree in Biology and Chemistry; Bowling Green State University
June 2019 – Present Clinical Instructor Housestaff, Resident Physician; The Ohio State University Wexner Medical Center, Physician Scientist Training Program
September 2018 – June 2019 Research Consultant; Whispergenics
May 2016 – August 2016 NIH NCI Postdoctoral Summer Intern; Center for Cancer Research; Laboratory of Genitourinary Cancer Pathogenesis
December 2014 – October 2015 Research Faculty; The Urology Institute; University Hospitals Case Medical Center
September 2014 – October 2015 NIH NIDDK Postdoctoral Fellow; Department of Urology; Case Western Reserve University School of Medicine
December 2011 – August 2015 Student Member, Research Faculty Member; Tumor Board for Genitourinary Cancers; University Hospitals Case Medical Center
February 2012 – July 2015 Head of Yeast Propagation and Management, Part-Time Brewer; Fat Head’s Brewery and Tap House, Middleburg Heights
January 2008 – May 2009 Adjunct Instructor, Introductory Chemistry and Biology; Arts and Sciences Department; Northwest State Community College, Archbold, OH
April 2007 – July 2009 Water Utilities Director (01/01/2008 to 07/05/2009); Water Treatment Plant Superintendent (04/25/2007 to 12/31/2007); Village of Ottawa, OH
August 2006 – March 2007 Medical Technologist, Mass Spectrometry Technician; Quest Diagnostics; Department of Toxicology and Forensics; Las Vegas, NV
September 2005 – August 2006 Quality Control Analyst, FTIR, GC/MS, HPLC Technician; ProCaps Laboratories; Quality Control Division; Henderson, NV
August 2004 – August 2005 Research Assistant (Craig Jensen, Ph.D. Laboratory) and Teaching Assistant (Honors General Chemistry Laboratory and Analytical Chemistry Laboratory); Department of Chemistry; University of Hawaii at Manoa; Honolulu, HI
May 2000 - August 2004 Water Treatment Plant Operator, Chemical and Microbiological Analyst; Village of Archbold Water Treatment Plant; Archbold, OH
Honor and awards
March 2018 Medical Student Travel Award – Ohio Psychiatric Physicians Association Annual Meeting
September 2016 Medical Student Travel Award – Association of Medicine and Psychiatry Annual Meeting
August 2015 – May 2018 Dorothy and Ashel Bryan Scholarship – UTCOM Merit-Based
August 2015 – May 2018 Dearce Koch Scholarship – UTCOM Merit-Based
August 2015 – May 2018 UT Health Science Bookstore Scholarship – UTCOM Merit-Based
April 2015 Postdoctoral Research Award – Research ShowCASE, CWRU
April 2015 Doctoral Excellence Award in Nutrition – School of Graduate Studies, CWRU
September 2014 Society for Basic Urological Research Fall Symposium Travel Award
May 2014 Podium Presentation Award – Biomedical Graduate Student Symposium, CWRU
May 2014 Graduate Student Research Honorable Mention Award – Research ShowCASE, CWRU
July 2013 Scientific Poster Presentation Award – Case Comprehensive Cancer Center Retreat, CWRU
May 2013 Poster Presentation Award – Biomedical Graduate Student Symposium, CWRU
May 2013 Graduate Student Research Award – Research ShowCASE, CWRU
August 2016 – Present Medical Student Affairs Committee; Association of Medicine and Psychiatry
April 2016 – May 2017 Hematology & Medical Oncology Chair; Internal Medicine Club; University of Toledo College of Medicine; Toledo, OH
April 2016 – May 2017 Treasurer; Psychiatry Club; University of Toledo College of Medicine; Toledo, OH
April 2016 – May 2017 Secretary; LGBTQ People in Healthcare; University of Toledo College of Medicine; Toledo, OH
August 2015 – May 2016 M1 Representative; Interprofessional Immersive Simulation Center; University of Toledo College of Medicine; Toledo, OH
August 2015 – May 2016 College of Medicine Representative; Institute for Healthcare Improvement, UT Health Science Campus Chapter; University of Toledo; Toledo, OH
October 2014 – May 2015 Postdoctoral Representative; Faculty Senate, Committee on Graduate Studies; Case Western Reserve University; Cleveland, OH
September 2007 - July 2009 Communications Secretary; Blanchard River Flood Mitigation Committee; Putnam County Citizen and Public Official Collaborative; Ottawa, OH
Teaching and mentoring
May 2014 - August 2014 Mentee: Raj R. Nanavaty; The Ohio State University; Department of Biological Sciences; CWRU Undergraduate Summer Research Program
May 2013 - May 2014 Mentee: Christine Z. Oak (co-mentorship); Case Western Reserve University; Department of Biology and Medical Anthropology; CWRU Undergraduate Senior Capstone Research Program
May 2012 - August 2012 Mentee: Tavaris Tucker (co-mentorship); John F. Kennedy High School; CWRU High School Student Scientific Enrichment and Opportunity Program
January 2008 - May 2009 Adjunct Instructor, Introductory Chemistry and Biology; Arts and Sciences Department; Northwest State Community College; Archbold, OH
August 2004 - May 2005 Teaching Assistant, Honors General Chemistry and Analytical Chemistry Laboratories; Department of Chemistry; University of Hawaii at Manoa; Honolulu, HI
Andrew Stiff, MD, PhD PGY-4
I was born and raised in Pittsburgh, Pennsylvania where my family still lives. My first research experience came as an undergraduate at the University of Pittsburgh in the lab of Dr. Rick Relyea studying ecology and evolutionary biology through the NSF REU program. While crawling around swamps collecting amphipod species for our experiments is worlds away from oncology, this experience showed me the importance of curiosity, mentorship, and how interesting and fun research can be. Looking back, this experience was clearly the first spark that started me on the road to becoming a physician scientist.
Following my undergraduate work I had the opportunity to continue my research in evolutionary biology at the University of Oklahoma. During this time I started volunteering at the Manos Juntas free clinic in Oklahoma City on Saturday mornings. This experience put me in direct contact with patients for the first time as I worked in triage to take their vitals and figure out why they needed to see the physician. Those Saturday mornings showed me how impactful physicians can be on their patient’s lives, and taught me the value of serving those in need. These interactions inspired me to pursue medicine as my career and ultimately led to me coming to Ohio State for medical school in 2011.
When I arrived at Ohio State for medical school I didn’t have specific plans for a prolonged research experience, but I was quickly intrigued by all of the amazing research that now surrounded me. Fortunately, I was able to meet Dr. Flavia Pichiorri who provided me with an excellent opportunity to work in her lab focused on multiple myeloma. I initially worked on a project aimed at improving risk prognostication for multiple myeloma patients by measuring circulating miRNA levels. Participating in this project exposed me to the world of molecular biology and cancer research for the first time. It also allowed me to interact with patients with incurable cancer, and see the incredibly important role research plays in improving the treatment of these patients and their quality of life. Following this I successfully applied for a Pelotonia Fellowship, and took a one year leave of absence from medical school to work on a project investigating the use of the oncolytic Reovirus for the treatment of multiple myeloma. This project found that expression of the Reovirus receptor JAM 1 was epigenetically regulated, and its expression could be increased by treatment of myeloma cells with clinically used histone deacetylase inhibitors. Upregulation of JAM 1 with HDAC inhibitors resulted in enhanced productive Reovirus infection of multiple myeloma cells in vitro and in vivo resulting in enhanced myeloma cell death and reduced disease burden in animal models. During this time I decided to apply to the Medical Scientist Training Program at Ohio State and was thankfully accepted as an advanced training applicant.
For my PhD work I had the great fortune to work in Dr. William E. Carson III’s lab investigating immune suppressive tumor associated myeloid cells, in particular myeloid derived suppressor cells (MDSC). The central aspect of my dissertation work was focused on studying the interaction of MDSC and NK cells. This work found that MDSC are capable of inhibiting important anti tumor NK cell functions including natural cytotoxicity, cytokine production, and antibody dependent cellular cytotoxicity. This occurred through a contact independent mechanism involving nitric oxide production by MDSC resulting in the nitration of tyrosine residues on signal transduction molecules within NK cells thus blocking their activation. This work also showed that inhibiting MDSC nitric oxide production or depleting MDSC resulted in improved NK cell function, and improved efficacy of antibodies that can activate NK cells such as trastuzumab and cetuximab. In Dr. Carson’s lab I also had the opportunity to participate in several highly translational projects aimed at identifying therapeutic agents capable of targeting MDSC to improve anti-tumor immune responses. One project investigated the role of Bruton’s Tyrosine Kinase (BTK) in the expansion and function of MDSC. This work discovered that MDSC express BTK, and that the BTK inhibitor ibrutinib could inhibit the expansion of MDSC and impair their immune suppressive function. Furthermore, combining ibrutinib with an antibody targeting PDL1 resulted in improved tumor control. This project provided the preclinical evidence to support the initiation of a phase I clinical trial of ibrutinib and nivolumab for patients with metastatic solid tumors that is currently open at Ohio State. Finally, I also participated in a project that investigated the role of Brd4 in MDSC expansion and function.
When I returned to medical school for my clinical years I quickly gravitated to Internal Medicine and Oncology as my career choice. While investigating residency programs the commitment to mentorship and innovative approaches to career development, the excellent clinical training, and the amazing resources available through The James and the Comprehensive Cancer Center made Ohio State’s PSTP a clear first choice for me. Over the eight years I have spent at Ohio State thus far I cannot say enough about how accessible and enthusiastic numerous faculty mentors have been including Dr. Carson, Dr. Baiocchi, and Dr. Byrd.
Furthermore, Columbus is a wonderful place to live and enjoy life outside of the hospital and lab. My wonderful wife and I have been able to comfortably purchase a home in Columbus. We also take full advantage of the ample running trails for exercise and green space to play with our dog located throughout the city. Columbus also offers a plethora of ever changing restaurants, bars, and breweries that are fun and affordable. We also make it a point to support all things Buckeyes when it comes to sports, and are sure to make it to a few Blue Jacket’s hockey games every season. Finally, we have been able to see some of our favorite musicians and discovered some new ones at the different music venues here in Columbus.
BS, University of Pittsburgh, Summa Cum Laude, 2009
PhD, The Ohio State University, Dissertation Committee: Dr. William E. Carson III, Dr. John C. Byrd, Dr. Robert A. Baiocchi, Dr. Aharon G. Freud, 2017
MD, The Ohio State University, Magna Cum Laude, 2019
Ohio State University Medical Scientist Training Program Student of the Year Award
Ohio State University Internal Medicine Research Award
American Society of Hematology Annual Meeting Abstract Achievement Award
Pelotonia Medical Student Fellowship
Ohio State Research Day Travel Award
Lane Schick Trust Scholarship for medical student cancer research at Ohio State University
Kyle Beckwith, MD, PhD PGY-5I grew up in a Temperance, Michigan just over the border from Toledo. After graduating from University of Michigan with a Biochemistry degree in 2009, I moved to Columbus to attend the Ohio State College of Medicine. Although I would eventually join the MD/PhD program, I had not yet discovered my love for research and initially began on the traditional MD track.
My first laboratory experience came as a college senior in the lab of Dr. Michael Uhler, where I studied how transcription factor co-expression influenced neuronal differentiation. Growing enthusiasm for research lead me to join the lab of Dr. Phillip Popovich as a medical student, shifting my focus to immune activation in the context of spinal cord injury. This work ultimately formed the basis of a Journal of Neuroscience publication and solidified my desire to become a physician scientist. My interest in immunology grew while in the Popovich lab, but I had also developed an affinity for oncology during medical school and intended to explore this area further. This led me to the lab of Dr. John Byrd and Dr. Natarajan Muthusamy, who agreed to support my application for a Pelotonia fellowship. Ultimately, this led me to pursue a PhD with a focus on cancer immunology.
During this time, I largely focused on the study of immunotherapy in Chronic Lymphocytic Leukemia (CLL). My thesis work revolved around novel immunotherapeutic strategies targeting the B-cell surface protein CD37. A significant portion of this work was published in Leukemia, where I described characterizing a novel transgenic mouse model of CLL expressing the human CD37 protein, facilitating the subsequent preclinical evaluation of various CD37-targeted therapies. In addition to the study of CD37, a considerable portion of my work involved the BTK inhibitor ibrutinib and chimeric antigen receptor (CAR) T-cells. Along with our collaborators at University of Pennsylvania, we found that ibrutinib could enhance both the in vivo efficacy and ex vivo generation of CAR T-cells, which was the subject of an article we published in Blood.
My future goal remains to pursue a career as a Hematologist and translational researcher, with my primary research interest being immunotherapy for hematologic malignancy. When applying for residency I sought a program that would support my future goals as a physician scientist. This meant finding an institution with not only a fantastic Hematology department, but also one that would provide a strong Internal Medicine foundation. In this regard, Ohio State was an excellent fit to continue developing both my clinical and research skills. Having spent several years in Columbus prior to residency, I was confident that this program would provide the tools needed to achieve my goals and knew the academic environment was one I could thrive within for years to come.