Judging by the number of competitive grants he received just this year, one might think that Viraj Sanghvi, Ph.D., is a longtime faculty member. In fact, Dr. Sanghvi joined the University of Miami Miller School of Medicine faculty as a tenure-track assistant professor of molecular and cellular pharmacology — his first faculty position — in late 2020.
In 2022 alone, Dr. Sanghvi, a member of the Tumor Biology Program at Sylvester Comprehensive Cancer Center, was awarded three large and prestigious grants. The National Institutes of Health (NIH) Maximizing Investigators Research Award (MIRA), a highly competitive R35 grant, is funding nearly $2 million over five years, for the project “Understanding Glycation: Sweet side of protein regulation”; the American Cancer Society’s Research Scholar Grant, titled “Understanding and Targeting Metabolic Deglycation in Liver Cancer,” is providing $792,000 over four years; and the Department of Defense Career Development Award has awarded about $385,000 over two years, for research titled “Deciphering and Targeting Metabolic Deglycation in Lung Cancer.”
All are focused on different aspects of a process called glycation, which is driven by one of foods’ main components, sugar (primarily glucose or its breakdown products). Overconsumption of sugar can lead to this process, in which glucose attacks normally functioning proteins.
While many have studied glycation’s role in chronic diseases like diabetes, Dr. Sanghvi is one of the few researchers studying how diet and glycation might play important roles in cancer development — especially liver and lung cancers.
“We know that one of the driving factors of cancer development today is overconsumption of high-sugar, high-fat, so-called Western diets, combined with a sedentary lifestyle. We postulate that the process of de-glycation helps to fuel the increased cancer risk. We also know de-glycation, the process of reversing glycation, can protect several cancer-related proteins, such as NRF2,” said Dr. Sanghvi, who made an important discovery leading to his research while completing post-doctoral research on liver cancer metabolism at Memorial Sloan Kettering Cancer Center (MSKCC).
A Key Discovery
In a study published in 2019 in the high-impact journal Cell, Dr. Sanghvi and colleagues at MSKCC discovered that the cancer-causing NRF2 protein is regulated by glycation.
“Glycation was not explored in cancer, and our discovery that cellular cancer-related protein can be attacked by glucose has important clinical implications,” Dr. Sanghvi said. “Getting a high-impact factor paper on a novel biology that had not been investigated in cancer before is what helped me transition to independence and acquire all the funding aimed at understanding why high-sugar diets make people more prone to cancer development.
“The idea is we develop tumors in the mice and feed them Western diets, like those consumed by humans. We then try to understand the extent of glycation in cancer cells: How do cancer cells evade that glycation damage, and can we therapeutically target these enzymes?” he said.
Grant Funding Success
Dr. Sanghvi currently has six active extramural grants, and says that a few factors have contributed to his grant funding success: training as a postdoc at one of the world’s largest cancer centers, which provided the guidance to become a successful principal investigator; being one of the few investigators working on a big problem with few treatment options; and having the support to pursue the research at Sylvester.
“I chose to come to Sylvester in part because I got good vibes early on about this being a collaborative environment. People told me how supportive Sylvester and the Miller School are for young PIs, and how much effort they put into their development. And I have found this to be true,” he said. “Drs. Kerry Burnstein, Wael El-Rifai, and Steve Nimer promote people who do high-risk, high-reward science, which is what I’m doing.”
Dr. Sanghvi is a shining example of what young PIs can do with optimal mentoring, including expert advice and guidance in developing successful grant applications, said Kerry Burnstein, Ph.D., professor and chair of the Department of Molecular and Cellular Pharmacology and associate director for education and training at Sylvester.
Moving from Mentee to Mentor
The next step for Dr. Sanghvi will be to help others achieve similar success. A critical aspect of career development for early-stage faculty, according to Dr. Burnstein, is the transition from being mentored to being the mentor. Dr. Sanghvi is active in the Sylvester Faculty Development Program, which fosters a collaborative, supportive environment to help new faculty develop mentoring skills that are essential for a successful scientific program and research career.
Sylvester is committed to supporting exceptionally creative scientists such as Dr. Sanghvi to pursue highly innovative, paradigm-shifting research, according to Wael El-Rifai, M.D., Ph.D., associate director for basic science at Sylvester and the John and Judy Schulte Senior Endowed Chair in Cancer Research.
“Sylvester invests in innovative ideas that have the potential for broad impact. Dr. Sanghvi’s recent funding from NIH with an R35 will shed light on the role of glycation in protein regulation. This will add a new perspective for understanding tumorigenesis and cancer cells that can potentially impact the diagnostic and therapeutic approaches,” Dr. El-Rifai said.