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Rachel Perry, PhD, BS

Assistant Professor

Research Summary

The Perry lab aims to determine how systemic metabolism intersects with immunometabolism to alter outcomes in cancer, sepsis, and other pathologic conditions.

Extensive Research Description

I am an Assistant Professor in Cellular & Molecular Physiology and Internal Medicine (Endocrinology) focusing on tumor metabolism as well as on the impact of systemic metabolism on the response to inflammatory, carcinogenic, and other insults. My training focused on the development and application of stable isotope tracer methodologies to measure hepatic oxidative flux rates, and to use these methods to examine (1) the mechanism by which hyperglycemia develops in poorly-controlled type 1 and type 2 diabetes, and potential therapeutic approaches to treat it, (2) the mechanism by which glycemia is defended during starvation, (3) the mechanism by which inflammation and alterations in the gut microbiota contribute to the pathogenesis of obesity and insulin resistance, and (4) the development of novel mitochondrial uncouplers to treat non-alcoholic fatty liver disease, liver fibrosis, type 2 diabetes, and liver cirrhosis.

My young laboratory draws upon my training in the mechanisms of maintenance of glycemia and in the development of stable isotope tracer methods to model these effects, to examine the mechanism by which obesity drives the development and progression of multiple tumor types. We have shown that insulin drives glucose uptake and oxidation, resulting in increased tumor growth in vivo and in vitro in obesity-associated tumor types, in a result that appears to translate to humans, and that insulin-lowering approaches (mitochondrial uncoupling, SGLT2 inhibition) slow colon and breast cancer growth by reversing hyperinsulinemia-induced increases in tumor glucose uptake and oxidation. Current work in our laboratory expands these analyses to understand the impact of metabolic dysfunction on substrate utilization in addition tumor types, both associated and unassociated with obesity, and in the interplay between immune cells and tumor cells. Both in the lab and in the greater Yale community, I have a strong commitment to teaching and mentoring. I currently mentor two high school students, an undergraduate, five Ph.D. students, and an Associate Research Scientist, and am the co-lead instructor of a graduate-level class in metabolism. As a mentor and a member of two graduate admissions committees, I am also deeply committed to achieving a diverse and equitable training environment within Yale and in the greater scientific community, and actively seek to promote those values throughout my work.

Coauthors

Research Interests

Hyperglycemia; Hyperinsulinism; Insulin Resistance; Magnetic Resonance Spectroscopy

Selected Publications