Mary Philip, MD, PhD
Assistant Professor of Medicine, Division of Hematology and Oncology, Department of Medicine
Assistant Professor, Department of Pathology, Microbiology, and Immunology
The immune system has enormous power to detect and eliminate pathogens; however, CD8 T cells specific for (mutated) tumor antigens found within solid tumors are often dysfunctional, allowing tumors to progress. Hallmarks of tumor-specific T cell (TST) dysfunction in mice and humans include the expression of inhibitory receptors (e.g. PD1, CTLA4) and loss of effector function. The clinical success of immune checkpoint blockade and adoptive T cell therapy in some cancer patients demonstrates the potential of TST to mediate anti-tumor responses; however, many patients fail to respond, or their responses are not long-lasting. Therefore, important challenges and questions remain, including how to predict which patients will have long-lasting responses to therapy and how to design new immunotherapies for those patients who do not respond.
My research group seeks to understand how the immune system interacts with developing cancers from the first mutagenic hit initiating carcinogenesis through progression to late-stage and metastatic tumors. We use clinically-relevant genetic cancer mouse models to understand the molecular and epigenetic regulatory mechanisms underlying TST dysfunction and to design and test cutting-edge strategies to override TST dysfunction to improve cancer immunotherapy. Projects aim to (i) elucidate the mechanisms driving early TST dysfunction, (ii) determine how antigen chronicity drives dysfunction programming in TST, and (iii) design and test strategies, including epigenome editing, to reprogram dysfunctional TST for immunotherapy.
Dr. Philip received her BS in Molecular Biophysics and Biochemistry from Yale University and her MD and PhD in cancer biology from the University of Chicago. Her thesis work in the laboratory of Dr. Hans Schreiber uncovered new mechanisms of tumor-specific antigen generation and presentation to T cells. She completed Internal Medicine Residency training at the University of Chicago before going to the Fred Hutchinson Cancer Research Center/University of Washington in Seattle for Hematology/Oncology fellowship training. There she received a NCI K08 career development award and an American Society of Hematology Scholar Award for her research in Dr. Janis Abkowitz’s lab on metabolic regulation of T cell development. Dr. Philip built on her knowledge of T cell differentiation to decipher mechanisms of T cell dysfunction in solid tumors after joining Dr. Andrea Schietinger’s group at Memorial Sloan Kettering Cancer Center. Her studies on how epigenetic programs define T cell dysfunction and therapeutic reprogramming in solid tumors were recently published in Nature (2017). Her clinical training and work has shaped and informed her laboratory research, and she would like to build on her strengths in cancer immunology and hematologic malignancies to care for patients undergoing hematopoietic stem cell transplant and/or immunotherapy. As a laboratory-based investigator and physician-scientist, Dr. Philip’s goal is to use clinically-relevant, cutting-edge mouse models of cancer to tackle important cancer immunology questions and to design more potent and safer immunotherapy strategies for cancer patients.