2022 GRANTEE: Rahul Shinde, PhD
The Wistar Institute
Research Project: Exploiting the Gut Microbiome to Improve Therapy Response in PDAC
Award: 2022 Pancreatic Cancer Action Network Career Development Award
Award Period: July 1, 2022 – June 30, 2024
Dr. Shinde is an assistant professor in Immunology, Microenvironment & Metastasis Program at The Wistar Institute. He obtained his DVM from Nagpur Veterinary College, India, and his PhD in immunology from the Augusta University. Before joining The Wistar Institute he trained as a postdoctoral fellow in the Tumor Immunotherapy Program at the Princess Margaret Cancer Center in Toronto, Canada.
Dr. Shinde is an immunologist with interest in characterizing key factors in the tumor microenvironment and gut microbiome that contribute to the refractory nature of cancer and target them for therapies. He studied how metabolic signals and innate immunity influence disease development. The goal of his laboratory is to identify and characterize metabolic pathways that are central to myeloid cell function and control of immune responses. His laboratory currently is pursuing two lines of investigation, both focused on pancreatic cancer. The first seeks to dissect how the host metabolism controls macrophage function, and the second seeks to understand the links between the gut microbiome and innate immune responses and how those impact pancreatic cancer progression and therapy response.
Unlike other tumor types, pancreatic cancer has been resistant to most immunotherapy efforts to date. A key tumor-fighting immune cell is the tumor-associated macrophage. Recent work shows that the strength of these macrophages is influenced, surprisingly, by bacteria that live in the gut. When gut bacteria digest food, they produce metabolites. These metabolites enter the bloodstream and go to tumors where they can strengthen, or weaken, immune cells.
Dr. Rahul Shinde and his team’s work strives to better understand this process so they can develop ways to intervene. They recently found that a particular metabolite called TMAO (Trimethylamine N-oxide) equips macrophages to fight tumors. In mice, treatment with TMAO shrinks pancreatic tumors.
For his Career Development Award project, Dr. Shinde will test the broad hypothesis that bacterial metabolites, like TMAO, can strengthen the immune system to fight pancreatic cancer and improve therapy response. The investigators will test this hypothesis using cell cultures and mouse models. Aim 1 seeks to understand whether TMAO bolsters the macrophages to strengthen other tumor-fighting immune cells. Aim 2 tests if treating mice with chemotherapy plus TMAO further shrinks tumors and slows metastasis. In the short term, these studies will strengthen the field’s understanding of how gut bacteria influence pancreatic cancer. In the longer term, this work may form the basis for new gut bacteria-based therapies or diet-based therapies that improve survival as well as quality of life of individuals with the aggressive and hard to treat pancreatic cancer.