Harshabad Singh, MBBS
Dana-Farber Cancer Institute
2019 William Raveis Charitable Fund Fellowship
Cancers involving the lower esophagus have dramatically increased in number over the last several decades. The reason for rise in this cancer is not completely understood; it may be related to smoking, alcohol, or even acid reflux. However, long before these esophageal cancers develop, the normal lining of the esophagus changes, possibly as a result of stomach cells migrating upward. This new tissue is called “Barrett’s esophagus” and is more likely to progress to cancer.. Dr. Singh proposes to investigate the origins of Barrett’s esophagus and understand its specific vulnerability to progress to cancer. This work may lead to new preventive strategies for esophageal cancers.
Can you please tell us about your research?
Cancers involving the lower esophagus (Esophageal adenocarcinomas) have dramatically increased in number over the last several decades. Long before these esophageal cancers arise, the normal esophageal multilayered squamous lining (or epithelium) is replaced by an epithelium with features of the intestine and is known as Barretts esophagus. My goal is to elucidate the source of Barretts esophagus and the mechanisms underlying its genesis.
Over the last year, using multiple next generation sequencing techniques on patient samples, we have demonstrated that Barretts represents a modified version of stomach epithelium which gains intestinal features. Sparked by this unexpected finding, we have become fascinated by cellular and tissue identity i.e. What makes an organ, that organ? How is that identity maintained? And how change in a tissue’s identity vis-à-vis stomach adopting features of intestine in its path to Barretts esophagus can lead to an increased cancer risk.
My ongoing work is focused on understanding some of these questions with a hope to explain the reasons behind the increase in this cancer and come up with preventative strategies.
You trained as a physician. What inspired you to get into research? Describe how your interactions with patients affect your research.
I was fortunate enough to train at one of the best cancer centers in the country for my oncology fellowship. At Dana-Farber Cancer Institute, I saw how cutting-edge research was directly being translated into new therapies, diagnostics and clinical trials to improve outcomes of patients. This time spent was incredibly inspiring and led me to participate in this endeavor of basic science research in order to advance therapies in gastro-intestinal cancers.
Now that I am spending a large amount of my time and effort in the laboratory, the interactions I have with my patients serve as a compass to orient my research work in the most meaningful and clinically relevant direction. Laboratory work also presents its own sets of challenges. For example, experiments not working, despite putting in months of effort with countless hours on the bench.
Personally, seeing my patients fight through so much more is a true inspiration to keep working harder and moving steadily towards my goal.
How important is the support from Damon Runyon and the William Raveis Charitable Fund to your career?
The Damon Runyon and William Raveis Charitable Fund support is critical to the work I am doing and I am incredibly thankful for their support. As an MD, it can be quite challenging to obtain early career funding given the lack of a prior PhD with a proven basic science track record. The Damon Runyon Physician-Scientist Training Award and the William Raveis Charitable Fund have provided me with an incredible opportunity to continue my work on Barretts esophagus, and their investment will hopefully allow me to transition to an independent investigator in the coming years. For me, this funding changed the course of my research path!
In the best possible scenario, how would your work impact cancer patients?
My work tries to answer two fundamental questions:
- Where is Barretts esophagus coming from and how?
- Why does it lead to an increased risk of esophageal cancer? My hope is answers to these questions will help us understand why this cancer occurs and ways to prevent its rise.
Dr. Singh received his medical degree from Punjab University, Chandigarh, India. He credits his family, many of whom are physicians, as his inspiration for attending medical school. He completed his training at Massachusetts General Hospital, where he received the Senior Resident Excellence in Teaching Award. Outside of the laboratory, he enjoys watching cricket, spending time with his wife and 2-year old son and exploring New England.