Building a research powerhouse in microbial pathogenesis and immunology
In early 2019, months before the global pandemic, Eugene Oltz, PhD, became chair of the Department of Microbial Infection and Immunity at The Ohio State University College of Medicine. His first task — initiate a vision to address the urgent and increasing prevalence of cancer, autoimmune disorders and disease due to bacteria, viruses and chronic inflammation.
In short order, this dynamic research department became a hub for interdisciplinary research in microbial pathogenesis and immunology across campus and within the greater scientific community. The existing faculty collaborated to hire eight new faculty who study a multitude of approaches to harness the immune system for destroying cancer, inhibiting autoimmune responses and fighting constantly evolving microbes.
“Decades of research have furthered our understanding of how the immune system serves as our most natural defense against cancer and pathogens of all sorts,” Dr. Oltz says. “This is revolutionizing the treatment of almost every disease.”
The onset of COVID-19 made it imperative to bring together outstanding scientists from disparate fields to develop new diagnostics, vaccines and other leading-edge treatments. To meet this critical need, the department expanded existing partnerships with Ohio State’s Infectious Disease Institute, Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Pelotonia Institute for Immuno-Oncology and Nationwide Children’s Hospital.
These interactions were galvanized further by a number of new venues for scientific exchange, including new pilot grant programs, faculty work-in-progress meetings, and regular seminars by students and postdoctoral researchers.
Dr. Oltz says that having an established infrastructure and some of the best scientific minds in the nation contributed to Ohio State receiving a $10 million grant from the National Cancer Institute of the National Institutes of Health to fund the Center for Serological Testing to Improve Outcomes from Pandemic COVID-19 (STOP-COVID). Better understanding the immune response to COVID-19 will translate into vaccination and therapeutic approaches, as this virus and others like it continue to escape our immune responses through mutation.
To enhance the college’s educational mission, the department launched MS in Immunology and Microbial Pathogenesis, a program focused on foundational and advanced knowledge of these fields, accompanied by a laboratory research practicum. A doctorate level program in Immunology and Immunotherapeutics will begin in 2023, focusing on basic and clinically applied aspects of research, including fundamental cellular and molecular immunology, immunology of infectious diseases, and systems and translational immunology.
Addressing immune system challenges
From developing mechanisms to prevent the destruction of immune cells during chronic responses against cancer or pathogens, to blocking a virus’ ability to enter a human host, researchers at Ohio State continue to push the boundaries of science.
Jacob Yount, PhD, associate professor of Microbial Infection and Immunity and program director of the Viruses and Emerging Pathogens Program Area at Ohio State’s Infectious Diseases Institute, investigates interferon-induced transmembrane protein 3 (IFITM3) to develop infection prevention approaches and therapies. This naturally produced protein can block all strains of influenza virus that have been evaluated in laboratories, as well as many other viruses, such as Ebola and West Nile.
“This single protein is particularly important for limiting the severity of influenza virus infections, which becomes apparent in patients with defective IFITM3 due to a genetic mutation,” says Dr. Yount. “Increasing the level of IFITM3 in cells prior to infection could potentially prevent flu infections and provide new tools to fight existing and emerging viral diseases.”
Adriana Forero, PhD, assistant professor of Microbial Infection and Immunity, heads a lab that identifies viral and host factors that promote maladaptive interferon responses and contribute to the development of immunopathologies.
“We’re interested in understanding the contribution of cell identity to the protective and potentially harmful effects of an unabated innate immune response,” Dr. Forero says. “This will reveal tissue-specific vulnerabilities in signal transduction cascades targeted by pathogens or disrupted in autoimmune and proliferative diseases, which can be exploited for the management of deleterious inflammation.”
In her lab, Fernanda Novais, PhD, assistant professor of Microbial Infection and Immunity, investigates the crosstalk between infected tissues and immunity. Her team focuses on host-directed therapies to treat cutaneous leishmaniasis. Antiparasitic drugs are often ineffective in the most severe forms of the disease, and in some cases, the magnitude of the disease can result from an uncontrolled inflammatory response rather than parasite replication.
“There’s substantial evidence that host-directed therapies are likely to be beneficial beyond autoimmune diseases and cancer, and thus should be a critical component in the armamentarium to modulate the severity of cutaneous leishmaniasis,” Dr. Novais says.
Dr. Oltz added that Ohio State is in a unique position to translate such discoveries into personalized treatments and vaccines that can mitigate or prevent the devastating effects of infection, emerging pathogens and immune responses.
“Infectious diseases and immune disorders represent the primary threats to human health,” Dr. Oltz says. “We’re poised to blaze new trails into the prevention and treatment of these health threats, many of which were once thought intractable.”
