Taking the Fast Track to Independence in Oncology

Rahul S. Shinde, DVM, PhD

I have long dreamed of operating my own laboratory and serving as a leader in scientific research. Toward the end of my postdoctoral fellowship in the Tumor Immunotherapy Program at Princess Margaret Cancer Center in Toronto, Canada, I published my first high-impact research paper in Nature Immunology. I began looking for opportunities in academia and saw ads for the new Caspar Wistar Fellows Program. What an intriguing opportunity to transition from postdoctoral fellow to independent scientist, I thought.

The Wistar Institute has an illustrious history, and I had always wanted to work at such an esteemed institution. I conducted further research and found the program was indeed a chance to enter a top research environment and take an accelerated path toward independence as a principal investigator (PI). I could refine my skill set and mature professionally while launching my own research program in a great academic setting and city.

When considering a fellowship, think about your goals: Where are you in your career? Where are you trying to go? What are the cultural values of the organization you’re considering? Who will be your mentor and guide your career? What is the environment beyond the organization? Can you reach out, collaborate, and meet other like-minded scientists at nearby institutions?

I joined Wistar as the first Caspar Wistar Fellow in June 2019 and moved to Philadelphia. It was a great honor and a very exciting time to join a boundary-pushing biomedical research institute with a rich history of discovery in cancer and immunology, vaccine creation, and infectious disease research. I’m getting to know the city’s robust and collaborative life sciences community and setting up my laboratory. I hired my first assistant in September.

A fast-tracked PI is quite different from a postdoctoral fellow. As a PI, I run my lab like my own business; for the first time, I have sole responsibility for managing funds and hiring people.

As a postdoctoral fellow, I was usually in charge of 1 main project and 1 side project, so it’s been an exciting leap at Wistar. On the fast track to a PI, I think and act with a much broader perspective. I get to choose and develop my own projects, and I’m currently working on 4. It’s important that I know the ins and outs of my field, so I’ve always got my head in a journal. I’m drafting foundation grants and preparing to submit federal grants by next summer. And of course, I will be working hard to publish my first paper as corresponding author.

I have joined the Immunology, Microenvironment, and Metastasis Program, and I’m part of a uniquely collegial, interdisciplinary scientific environment with very strong expertise in tumor immunology that will be a critical source of know-how and guidance as I explore my own scientific hypotheses.

My research centers on therapy options for patients with pancreatic cancer, which are consistently limited and largely ineffective. I am interested in characterizing molecular mechanisms that control macrophage immunosuppressive behavior and developing tools to target and open new therapeutic avenues for the disease.

Pancreatic cancer is surrounded by a highly immunosuppressive tumor microenvironment (TME) with a dense fibrotic stroma that limits drug penetration and effector T-cell responses. Macrophages are a major immune cell infiltrate, important for driving immunosuppression, T-cell dysfunction, and profibrotic events.

One facet of my research is exploring how alterations in the cell metabolism of macrophages affect their function. My findings so far highlight the importance of branched-chain amino acids (BCAAs) and their catabolism mediated by Kruppel-like factors (KLFs) in shaping the functional responses of macrophages in the tumor. My lab is interested in expanding our knowledge of KLF biology and BCAA catabolism in macrophages affecting cancer progression and therapy resistance.

Additionally, commensal microbiota are critical in shaping the TME and tumor progression.

Recent advances in the field indicate that host, dietary, and environmental factors contribute to changes in the microbiome. I am interested in identifying key factors that influence the healthy-symbiotic or disease modulating—dysbiotic microbiome and contribute to the refractory nature of the disease to eventually target these factors for therapies.

Beyond thinking about my research, I’m surrounded and learning from Wistar’s scientific leadership. I have regular meetings with Dmitry Gabrilovich, MD, PhD, the Christopher M. Davis Professor and leader of the Immunology, Microenvironment, and Metastasis Program, and David B. Weiner, PhD, executive vice president, director of the Vaccine & Immunotherapy Center, and the W.W. Smith Charitable Trust Professor in Cancer Research.

The vibrant atmosphere at Wistar is helping me begin collaborations with Wistar faculty as well as scientists at the University of Pennsylvania. I continue scientific exchanges with my mentors, Tracy McGaha, PhD, at the University of Toronto, and David Munn, MD, at Augusta University’s Georgia Cancer Center.

The Caspar Wistar Fellows Program is providing me with the best foundation to succeed. I’m gaining momentum and advancing my academic career with mentoring from top scientists in my field, in an environment that nurtures collaboration, creativity, and excellence. I look forward to obtaining federal grant funding and publishing quality research in top-tier journals. I want to achieve the skill sets needed to establish an innovative lab, solve key questions in the field of cancer, and one day, repay my good fortune by mentoring future generations of scientists.

This article was written by Rahul S. Shinde, DVM, PhD, Caspar Wistar Fellow, Immunology, Microenvironment and Metastasis Program, The Wistar Institute.