The research conducted in the Department of Microbial Infection and Immunity (MI&I) is driven by the global problems related to infectious diseases and the nature of the immune responses. This research is necessary in order to develop tools for new diagnostics, therapies, and vaccines. In the past, researchers and clinicians have been faced with the challenge of staying ahead of common epidemics and pandemics, such as influenza and tuberculosis. Recently, a new breed of antibiotic-resistant pathogens and emerging pathogens has public health officials concerned as well.

In addition to these diseases, infections that accompany various other conditions and medical procedures and the costs associated with these infections, are among the highest in America's hospitals. With expertise in host-microbe interactions, innate and adaptive immunity, and therapeutics, the Department of MI&I serves as the hub for faculty striving toward similar goals of studying various aspects of microbial infection and immunity. The department provides teaching and research opportunities in microbe-host interactions and immunology and educates the general public with regard to information and knowledge of infectious diseases. Academic medical centers are in a very unique position to better understand these pathogens and the host response, and translate discoveries into personalized treatments and vaccines that can mitigate or prevent the often times devastating effects of these diseases.

Highlighted Research

Dr. Hazem Ghoneim, an Assistant Professor of Microbial Infection and Immunity and member of the Pelotonia Institute for Immuno-Oncology, was awarded $3.2 million from the National Institute of Allergy and Infectious Diseases for his proposal to investigate molecular mechanisms underlying T-cell exhaustion and develop novel therapeutic approaches to epigenetically reprogram dysfunctional CD8 T cells for boosting T-cell immunotherapy against cancer or chronic infections. 

Immune cells called CD8 T cells are critically important in the immune system’s efforts to eliminate cancer cells and viral infected cells from the body. CD8 T cells are also key players in immunotherapies called immune checkpoint blockade and CAR T-cell therapy. “When killer T cells become severely dysfunctional, they are unable to effectively clear cancer or viral infections, and they do not respond well to immunotherapies,” says Dr. Ghoneim. Dr. Ghoneim’s early work showed that dysfunctional T cells acquire heritable epigenetic programs that silence T cell-related stemness and function genes, restraining responses to immune checkpoint blockade (Ghoneim, et al. Cell 2017). “Epigenetic programming is a fundamental molecular mechanism that regulates cell's transcriptional output and controls cell's identity and fate commitment. It involves structural changes in the chromatin that modulate chromatin accessibility and gene expression programs without altering DNA sequences.” explains Dr. Ghoneim. Recently, Dr. Ghoneim and his team revealed a significant role of the microenvironmental signals in imprinting these epigenetic changes in dysfunctional T cells. In addition, they discovered a novel therapeutic approach to unlock T cell responses to cancer immunotherapy by rebalancing of TGFB1/BMP signals (Saadey, et al. Nature Immunol 2022). 
 
This new research will determine how TGFβ1 signals orchestrate epigenetic programming in severely dysfunctional T cells; and whether modulating microenvironmental signals can epigenetically revive the memory potential in dysfunctional T cells. These studies will provide important insights into how epigenetic programs of exhaustion can be thwarted or reversed in CD8 T cells to enhance T cell immunotherapies against cancer or chronic viral infections.

For more information--Lab website