2021 Grantee: Ralph Francescone, PhD
Fox Chase Cancer Center
Research Project: Metabolic Link to Immunosuppressive Fibroblasts in Pancreatic Cancer
Award: 2021 Pancreatic Cancer Action Network Career Development Award in memory of Skip Viragh
Award Period: July 1, 2021 – June 30, 2023
Dr. Ralph Francescone is a research assistant professor at Fox Chase Cancer Center (FCCC) in Philadelphia, PA. Ralph received his BS in Biochemistry from Merrimack College in North Andover, MA, where he studied how mitochondria (the powerhouse of the cell) influence tumor cell function. From there, he traveled to UMASS Amherst to purse a PhD in Molecular and Cellular Biology under the mentorship of Dr. Rong Shao, where he studied the mechanisms of tumor vasculature in relation to brain cancer progression and stemness. After obtaining his PhD, he then joined the laboratory of Dr. Sergei Grivennikov at FCCC as a post-doctoral fellow, where he investigated how inflammation driven by cancer cells affected tumorigenesis. Finally, after spending two years in the Grivennikov Lab, he moved to Dr. Edna Cukierman’s laboratory in 2015 at FCCC, where he has been investigating the role the tumor microenvironment (non-tumor cells and foundational proteins that make up the organ) plays in the initiation and progression of pancreatic cancer. FCCC is also where Dr. Francescone met his partner in life (and science!), Dr. Débora Barbosa Vendramini Costa.
Currently, the team is interested in investigating how a certain population of cells in the pancreas, known as fibroblasts, inhibit the function of “good” immune cells that would normally attack the tumor. The ultimate goal of the research is to integrate large immune and metabolic profiles generated from mice and patients to develop better prognostic, diagnostic and therapeutic options to combat this deadly disease.
One of the reasons that pancreatic cancer is so deadly is due to the unique environment that the cancer cells grow in. Many non-cancerous cells also inhabit the pancreas, such as fibroblasts, which help build tissue structure and support local cell growth, maintaining a healthy pancreas. These cells become hijacked during pancreatic cancer and often promote the growth of the tumor by supplying the cancer cells with nutrients and proteins that help them survive, as well as blocking “good” immune cells, such as natural killer and T-cells, from attacking and removing the tumor.
Recently, Dr. Francescone discovered a link between the proteins called enzymes that help fibroblasts supply nutrients to tumor cells with their ability to also shut off the good components of the immune system. Therefore, the goal of this proposal is to deeply explore the link between metabolism (the use of nutrients for energy) and immune regulation in fibroblasts. Dr. Francescone and his team seek to learn how to reprogram these noncancerous fibroblasts so that they do not provide nutrients to cancer cells and do allow anti-tumor immune cells to migrate into the tumor and eliminate cancer cells.
Their approach centers around using a gene-editing technique known as CRISPR to remove key metabolic enzymes from fibroblasts, and then studying how they regulate the immune system and tumor growth, both in cell and in animal models. Additionally, Dr. Francescone would like to develop a diagnostic panel of metabolites (substances produced during metabolism, or nutrient breakdown) and immune regulating factors from the fluid of tumors (in mice and humans), which has the potential to detect cancer early or determine prognosis of patients. Thus, the investigators hope to uncover novel mechanisms that drive pancreatic cancer at the cellular level, while also providing a potential set of diagnostic and prognostic markers that could directly help patients in the clinic.