Reflecting on my career as a physician-scientist, I’m reminded of guiding reasons why this path has aligned my interests and strengths. In my practice, I balance caring for bladder and kidney cancer with discovery and translational research that integrates the fields of epigenetics and immunology.
An early love of science
An inclination toward science and STEM-related studies was an ingrained part of my life growing up in India. My father retired as a chief engineer, my mother had a master’s degree in geology and my grandfather was a renowned biochemist working in academia. Having these role models, along with an inherent curiosity and love of science, made studying medicine a natural choice.
Pursuing curative medicine
My medical training was where my interest in pursuing research began. I completed training in a tertiary medical center where I saw a large volume of patients. While it was a privilege taking care of these patients, oftentimes I felt limited in terms of the care we could offer as providers. This was because of a lack of curative medicine for most of the diseases we were treating. It was then that I knew I wanted to couple both medicine and science, and pursue research.
I completed my PhD at Houston-based Baylor College of Medicine’s Department of Immunology. Prior to joining Houston-based University of Texas MD Anderson Cancer Center for a medical oncology fellowship, I completed my clinical residency in internal medicine at the University of Pittsburgh Medical Center, where I found myself surrounded by support from other physician-scientists, especially Padmanee Sharma, MD, PhD — a renowned physician-scientist.
These combined experiences cemented my plan to pursue this path. Since joining MD Anderson, I’ve celebrated a number of significant career milestones, including an appointment as an inaugural member of the James P. Allison Institute, a visionary research and innovation hub created to conduct groundbreaking science and integrate immunobiology across all disciplines.
Learning from every patient
The role of physician-scientist comes with unique privileges and challenges. It enables us to learn from every patient in a distinct way — learning from how they respond to treatments and how that response evolves. Working as a scientist in the lab to be able to understand and delineate potential mechanisms underlying distinct patient profiles is an incredible opportunity. With the patient volumes we have at MD Anderson, we have tremendous opportunities to learn from identifying unmet needs and assessing how we can improve cancer care.
Although the depth and breadth of our patient volumes was a major draw for me to join the institution as a faculty member after completing my clinical fellowship, the most important reason that I stayed was because of MD Anderson’s unique research model and collaborative environment. A dynamic dialogue and connection between physicians, scientists and physician-scientists is critical to my work in my role, and to our shared mission. The collaborative aspect is very important for early career investigators.
Advancing personalized medicine
My work bridges clinical expertise with translational research, deepening our understanding of combination therapy and predictive biomarkers. Immune checkpoint therapy has been a paradigm shift in cancer care. This is one of the treatments that can result in durable responses, including cure, in some patients. But the percentages of patients who actually benefit and obtain durable clinical benefit or cure is relatively small. Therefore, my focus is on understanding why some patients respond and others do not. My current research focuses on uncovering key epigenetic factors involved in primary and adaptive resistance to immunotherapy.
Tumor microenvironments are unique to each patient. Understanding the cross-talk within a tumor microenvironment allows us to identify the resistance pathways in patients who did not respond to a certain therapy, thus informing how we should design and rationalize subsequent rounds of combination therapy. Moreover, based on our understanding of biomarkers, we can tailor treatment strategies for patients displaying certain attributes. Ultimately, translational as and fundamental research are enabling us to deliver personalized, precision oncology.
Moving discoveries from bench to bedside
During my medical oncology fellowship at MD Anderson, I developed a strong interest in understanding the pathways that govern changes in the T cell function and subsequently dictate response to immune checkpoint therapy.
We found that the expression of the epigenetic enzyme EZH2 increases in T cells of patients treated with anti-CTLA4, a type of immune checkpoint therapy. To understand the functional relevance, we conducted a series of bench experiments which showed the inhibition of the EZH2 enzyme can improve survival in murine models across different tumor types.
Building on these findings, we conducted a phase 1/2 clinical trial to understand if we can combine an EZH1/2 inhibitor with anti-CTLA4 to improve responses to immune checkpoint therapy. We’ve completed enrollment for the trial, and we are almost ready to report the results.
From clinical observation to fundamental research to delivering novel treatment strategies to our patients, as a physician-scientist, these are the most heartwarming moments in one’s career.
Great discoveries and innovation hinge on our understanding of fundamental mechanisms. Moving forward, physician-scientists will play a key role in addressing some of the most pressing priorities in biomedical research. I would encourage those interested in pursuing this career path to develop their scientific temperament for fundamental research.
The lab and the clinic may seem like two different worlds, but when they come together, that’s where transformation happens — for science, for medicine, and most importantly, for patients. I look forward to the future of our field and working together to accelerate clinical research and innovation for the benefit of our patients.
