Supporting Local Initiatives and Community Development
HBF Spotlight: Srivatsan Raghavan, MD, PhD
Meet Dr. Sri Raghavan!
Dr. Raghavan is an assistant professor, medical oncologist, and physician-scientist at Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School. A 2020 Hopper-Belmont Inspiration Award recipient, Dr. Raghavan is widely respected for his work treating patients with gastrointestinal cancers. In addition to his clinical practice, he conducts basic and translational research focused on understanding disease mechanisms and developing innovative therapeutic approaches for pancreatic and biliary cancers.
https://www.dana-farber.org/find-a-doctor/srivatsan-raghavan
What degrees have you earned, and from which institutions?
B.S., M.S. Chemical Engineering – MIT; MD, PhD (Biomedical Engineering) – Johns Hopkins University
What inspired you to pursue cancer research?
My interest in cancer research arose through a combination of my clinical interests in oncology and longitudinally caring for patients with cancer, seeing the limitations of current treatments in the setting of frequent disease recurrence, and the opportunity to merge my research background with clinical and translational opportunities to hopefully develop new therapeutic approaches and improve care for patients in the future.
What inspired you to pursue cancer research?
My interest in cancer research arose through a combination of my clinical interests in oncology and longitudinally caring for patients with cancer, seeing the limitations of current treatments in the setting of frequent disease recurrence, and the opportunity to merge my research background with clinical and translational opportunities to hopefully develop new therapeutic approaches and improve care for patients in the future.
How did you get started in cancer research?
While my PhD research was in biomedical engineering and vascular biology, during medical school and medical residency, I became interested in pursuing a career in solid tumor oncology. As part of my medical oncology fellowship at Dana-Farber Cancer Institute, I joined Dr. Bill Hahn’s lab for post-doctoral research training in cancer biology.
Can you briefly describe your current research focus?
My laboratory investigates how cancer cell state plasticity and interactions with the tumor microenvironment shape drug response and resistance in pancreatic and biliary tract cancers, with the goal of developing a deeper understanding of tumor evolution and identifying new therapeutic strategies for patients. We leverage a variety of cutting-edge experimental and computational approaches including functional genomic CRISPR and pharmacologic screens and single-cell genomic sequencing.
What do you find most exciting or rewarding about your work?
Cancer research is fast paced and evolves quickly, uses a lot of novel technologies, and has the potential for immediate impact via new diagnostic tools and therapies. There is a close relationship in oncology between basic research and eventual clinical translation. In addition, I find working with a team of skilled scientists and trainees whom I mentor to be both stimulating and enjoyable. Lastly, caring for patients during what is often one of the most difficult periods of their lives can be challenging but remains deeply rewarding.
Have you had any key mentors or collaborators who shaped your path?
As with anyone who pursues an academic scientific career, I have had numerous mentors during my scientific career who have supported my scientific and professional development. It really takes a community of supportive people to reach this point.
Undergraduate mentors - Paul Laibinis, Ed Merrill, Guillermo Ameer/Robert Langer. I performed undergrad research at MIT in all of their labs, and these scientists shaped my early interests in chemical, polymer, and biomedical engineering.
PhD advisor - Chris Chen. The Chen lab was a unique environment with a blend of biologists and engineers, and really provided the foundation for my interests in biological research. While my PhD work with Chris focused on endothelial and normal epithelial biology, I started getting exposure to cancer biology, and this laid the groundwork for my eventual pursuit of a career in oncology.
Post-doctoral training - Bill Hahn, Brian Wolpin, Andy Aguirre, Sangeeta Bhatia, Alex Shalek, Stuart Schreiber, Charlie Fuchs, Nabeel Bardeesy. I’ve been fortunate to work with many accomplished scientists during my post-doc and early faculty career. Bill Hahn and Brian Wolpin were key mentors and supporters of my work and career development, and both continue to serve in this role. Bill gave me the freedom and time to pursue challenging projects involving pancreatic cancer organoid biology and single-cell RNA-sequencing. I’ve also been able to collaborate with the other scientists listed here, and these interactions have expanded my knowledge base and shaped my approach to scientific research.
Moving forward, I hope to serve in this role for future trainees and believe this is one of the most important aspects of my job.
What has been your most meaningful contribution or project?
We identified that pancreatic cancer cell states are shaped by both cell-intrinsic and tumor microenvironmental signals, and that these cell states directly impact drug response. We are now investigating these findings further with the goal of identifying new therapeutic strategies to target cancer cell state and plasticity. In cholangiocarcinoma, we identified a subset of patients with a novel FGFR2 extracellular deletion that confers sensitivity to FGFR inhibitors. This study demonstrated that patients harboring these alterations who were previously not included in clinical trials could benefit from FGFR-targeted agents, opening up a new range of therapies for this rare genomically-defined subset of cholangiocarcinoma patients. We are extending our research in biliary tract cancers using clinical cohorts to identify transcriptional variation across these diverse malignancies.
How do you hope your research will impact cancer care or treatment?
We have several goals in our research. One is to identify new therapeutic targets and associated biomarkers to guide their usage for patients with pancreatic and biliary tract cancers. We are specifically focusing on defining cancer cell states across GI cancers with the hope that these can be used as biomarkers in conjunction with genomic features to both select therapies and define mechanisms of therapeutic resistance. We are also investigating cancer cell states in biliary tract cancers, a diverse set of rare malignancies that includes intra- and extra-hepatic cholangiocarcinoma and gall bladder carcinoma. Together we hope that our studies in both pancreatic and biliary tract cancers will provide a deeper understanding of cancer evolution and drug resistance and uncover new ways to target these challenging diseases and thereby benefit patients.
What challenges have you faced, and how did you overcome them?
There were many times during my graduate and post-doctoral training when I thought that an academic career wouldn’t work out. In academic environments like Harvard, it’s easy to become overly stressed out by all of the highly accomplished people around you. It’s important to sometimes take a step back, realize that we are in a very unique academic microcosm, acknowledge your own day-to-day successes, and realize that there are many satisfying career options out there. In my case, by staying focused, learning to enjoy the process rather than becoming overly focused on the end goal, and being fortunate to have great mentors, wonderful colleagues, and a supportive family, I was able to transition to my faculty position, and now I hope to support my own trainees through this process.On the more personal side, as I’ve gotten older, my family has been directly affected by cancer and other chronic illnesses. These personal experiences have helped me to more deeply understand the impact of these diseases on patients and their families, and really drives home the importance of the scientific community’s work in trying to make advances that improve outcomes for patients.
Where do you see your research heading in the next 5–10 years?
We are trying to systematically build a map that relates transcriptional drivers of cancer cell state variation to cellular functions and properties (e.g., resistance to a drug or microenvironment signal), and hope in the next several years to have a deeper understanding of how pancreatic and biliary tract cancers adapt and evolve, from initiation across different tumor stages and therapies. Through this mapping effort, we hope to identify novel drug targets for therapeutic development, and in parallel are exploring new methods for cell state biomarker discovery that will enable clinical translation of this strategy.
What advice would you give to others just entering the field?
Pursuing a scientific research career is a long road and requires a lot of patience and persistence. It’s important to take time to appreciate the small wins, to develop a community across your workplace and with others in the field as the people around you are what make work more enjoyable, and to try to maintain a balance between work and home life. In the long run, while challenging, scientific careers can be very rewarding, especially as you have opportunities to see how your and others’ work in your field impact the scientific community at large, your own trainees, and patients.
All of us at HBF thank Dr. Raghavan for his innovative and breakthrough approaches to solving the toughest cancer challenges. Importantly, his commitment and support of this Foundation’s mission of recognizing and supporting early career cancer researchers has been, and continues to be, truly appreciated.