Rachel Perry, PhD, BS
Research & Publications
Biography
News
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
- Uncoupling Hepatic Oxidative Phosphorylation Reduces Tumor Growth in Two Murine Models of Colon Cancer.Wang Y, Nasiri AR, Damsky WE, Perry CJ, Zhang XM, Rabin-Court A, Pollak MN, Shulman GI, Perry RJ. Uncoupling Hepatic Oxidative Phosphorylation Reduces Tumor Growth in Two Murine Models of Colon Cancer. Cell Reports 2018, 24: 47-55. PMID: 29972790, PMCID: PMC6056247, DOI: 10.1016/j.celrep.2018.06.008.
- Leptin Mediates a Glucose-Fatty Acid Cycle to Maintain Glucose Homeostasis in Starvation.Perry RJ, Wang Y, Cline GW, Rabin-Court A, Song JD, Dufour S, Zhang XM, Petersen KF, Shulman GI. Leptin Mediates a Glucose-Fatty Acid Cycle to Maintain Glucose Homeostasis in Starvation. Cell 2018, 172: 234-248.e17. PMID: 29307489, PMCID: PMC5766366, DOI: 10.1016/j.cell.2017.12.001.
- Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome.Perry RJ, Peng L, Barry NA, Cline GW, Zhang D, Cardone RL, Petersen KF, Kibbey RG, Goodman AL, Shulman GI. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome. Nature 2016, 534: 213-7. PMID: 27279214, PMCID: PMC4922538, DOI: 10.1038/nature18309.
- Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats.Perry RJ, Zhang D, Zhang XM, Boyer JL, Shulman GI. Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats. Science (New York, N.Y.) 2015, 347: 1253-6. PMID: 25721504, PMCID: PMC4495920, DOI: 10.1126/science.aaa0672.
- Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes.Perry RJ, Camporez JP, Kursawe R, Titchenell PM, Zhang D, Perry CJ, Jurczak MJ, Abudukadier A, Han MS, Zhang XM, Ruan HB, Yang X, Caprio S, Kaech SM, Sul HS, Birnbaum MJ, Davis RJ, Cline GW, Petersen KF, Shulman GI. Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes. Cell 2015, 160: 745-758. PMID: 25662011, PMCID: PMC4498261, DOI: 10.1016/j.cell.2015.01.012.
- Leptin's hunger-suppressing effects are mediated by the hypothalamic-pituitary-adrenocortical axis in rodents.Perry RJ, Resch JM, Douglass AM, Madara JC, Rabin-Court A, Kucukdereli H, Wu C, Song JD, Lowell BB, Shulman GI. Leptin's hunger-suppressing effects are mediated by the hypothalamic-pituitary-adrenocortical axis in rodents. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 13670-13679. PMID: 31213533, PMCID: PMC6613139, DOI: 10.1073/pnas.1901795116.
- Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidation.Rabin-Court A, Rodrigues MR, Zhang XM, Perry RJ. Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidation. PloS One 2019, 14: e0218126. PMID: 31188872, PMCID: PMC6561592, DOI: 10.1371/journal.pone.0218126.