Molecular mechanisms of insulin signaling, insulin resistance, and metabolism
metabolism, insulin, diabetes, obesity, AKT, mTORC1
My research interests are focused on the regulation of metabolism by hormones and nutrients, with a particular emphasis on a master regulator of organismal anabolic metabolism, insulin. Alterations in insulin action underlie metabolic disease and lead to the development of deadly vascular and neuronal complications. Through the use of various techniques encompassing molecular biology, biochemistry, metabolomics, genome-wide transcriptional techniques and whole-animal physiology, the long-term goals of my research program are to decipher the underlying mechanisms driving metabolic deregulation during disease and identify new therapies that improve metabolic control.
Matthew Gavin (Research Specialist)
Natasha Jaiswal Ph.D. (Postdoctoral Researcher)
Jaclyn Welles Ph.D. (Postdoctoral Researcher)
Kahea Uehara (PhD student, BMB graduate group)
Jaimarie Sostre (PhD student, CAMB graduate group)
Dominic Santoleri (PhD student, BMB graduate group)
Anna Garcia Whitlock M.D. (PhD student, CAMB graduate group)
Megan Stefkovich, (PhD student, CAMB graduate group)
Jennifer Guo (Penn undergraduate)
Olivia Ong (Penn undergraduate)
Sostre-Colón J, Gavin MJ, Santoleri D, Titchenell PM.: Acute Deletion of the FOXO1-dependent Hepatokine FGF21 Does not Alter Basal Glucose Homeostasis or Lipolysis in Mice. Endocrinology 163: bqac035, May 2022.
Jaiswal N, Gavin M, Loro E, Sostre-Colón J, Roberson PA, Uehara K, Rivera-Fuentes N, Neinast M, Arany Z, Kimball SR, Khurana TS, Titchenell PM.: AKT controls protein synthesis and oxidative metabolism via combined mTORC1 and FOXO1 signalling to govern muscle physiology. J Cachexia Sarcopenia Muscle Feb 2022.
Uehara K, Sostre-Colón J, Gavin M, Santoleri D, Leonard KA, Jacobs RL, Titchenell PM.: Activation of Liver mTORC1 Protects Against NASH via Dual Regulation of VLDL-TAG Secretion and De Novo Lipogenesis. Cell Mol Gastroenterol Hepatol 13: 1625-1647, Feb 2022.
Gosis BS, Wada S, Thorsheim C, Li K, Jung S, Rhoades JH, Yang Y, Brandimarto J, Li L, Uehara K, Jang C, Lanza M, Sanford NB, Bornstein MR, Jeong S, Titchenell PM, Biddinger SB, Arany Z.: Inhibition of nonalcoholic fatty liver disease in mice by selective inhibition of mTORC1. Science 376: eabf8271, Apr 2022.
Sostre-Colón J, Uehara K, Garcia Whitlock AE, Gavin MJ, Ishibashi J, Potthoff MJ, Seale P, Titchenell PM.: Hepatic AKT orchestrates adipose tissue thermogenesis via FGF21-dependent and -independent mechanisms. Cell Rep 35: 109128, May 2021.
Garcia Whitlock AE, Sostre-Colón J, Gavin M, Martin ND, Baur JA, Sims CA, Titchenell PM.: Loss of FOXO transcription factors in the liver mitigates stress-induced hyperglycemia. Mol Metab Sep 2021.
Zhao S, Jang C, Liu J, Uehara K, Gilbert M, Izzo L, Zeng X, Trefely S, Fernandez S, Carrer A, Miller KD, Schug ZT, Snyder NW, Gade TP, Titchenell PM, Rabinowitz JD, Wellen KE.: Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. Nature Mar 2020.
Jaiswal N, Gavin MG, Quinn WJ 3rd, Luongo TS, Gelfer RG, Baur JA, Titchenell PM.: The role of skeletal muscle Akt in the regulation of muscle mass and glucose homeostasis. Mol Metab Oct 2019.
Santoleri D, Titchenell PM.: Resolving the Paradox of Hepatic Insulin Resistance. Cell Mol Gastroenterol Hepatol Nov 2019.
Quinn WJ 3rd, Wan M, Shewale SV, Gelfer R, Rader DJ, Birnbaum MJ, Titchenell PM.: mTORC1 stimulates phosphatidylcholine synthesis to promote triglyceride secretion. J Clin Invest 127: 4207-4215, Nov 2017.
Titchenell PM, Lazar MA, Birnbaum MJ.: Unraveling the Regulation of Hepatic Metabolism by Insulin. Trends Endocrinol Metab July 2017.
Titchenell PM, Quinn WJ, Lu M, Chu Q, Lu W, Li C, Chen H, Monks BR, Chen J, Rabinowitz JD, Birnbaum MJ.: Direct Hepatocyte Insulin Signaling Is Required for Lipogenesis but Is Dispensable for the Suppression of Glucose Production. Cell Metab 23: 1154-1166, Jun 2016.
Titchenell PM, Chu Q, Monks BR, Birnbaum MJ.: Hepatic insulin signalling is dispensable for suppression of glucose output by insulin in vivo. Nat Commun 6: 7078, May 2015.
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Last updated: 04/26/2022
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