Dr. Cox is currently an Assistant Professor in the Center for Metabolic & Degenerative Diseases at the Institute of Molecular Medicine of McGovern Medical School at UTHealth. He received his B.MSc. in Physiology from the University of Western Ontario (UWO) in Canada in 2004. He also received his Ph.D. in Physiology from UWO, studying maternal dietary influences on fetal pancreas development and islet beta cell regeneration. He moved to Houston and Baylor College of Medicine (BCM) for his Postdoctoral studies focused on beta cell regeneration in aging, while extensively exploring various drugs (GLP-1 analogs), putative hormones (betatrophin), and physiologic models (obesity) to identify signals that regulate beta cell proliferation. He expanded his training as an Instructor at BCM performing translational studies aimed at blocking the negative effects of inflammation on glucose metabolism and insulin sensitivity in diabetes. At UTHealth, Dr. Cox’s laboratory is actively studying the influences of nutrient and hormone signaling on islet function, beta cell metabolism and regeneration.


Postdoctoral Fellowship
Baylor College of Medicine
Ph.D. in Physiology
University of Western Ontario
B.MSc. in Physiology
University of Western Ontario

Areas of Interest

Research Interests

Diabetes is marked by a relative or absolute deficiency of insulin-producing beta cells. Our work is focused on identifying mechanisms governing pancreatic islet function and beta cell proliferation that can be reliably targeted to restore functional beta cell mass for people living with diabetes. To address our objectives, we employ state-of-the-art techniques including transcriptomics, metabolomics, and microscopy with unique genetic mouse models and human islets. We have two primary projects in the lab studying paracrine signaling in islet function and transcriptional regulation of beta cell proliferation.


Project #1. The delta cell is uniquely positioned in the islet to integrate local signals and circulating nutrient cues to regulate alpha and beta cell function. Delta cells exert inhibitory effects on alpha and beta cells through somatostatin (SST) secretion. Paracrine actions of SST form a negative feedback loop to restrain hormone secretion and maintain glucose homeostasis. In type 2 diabetes (T2D), delta cell responses to ambient glucose are disproportionate and consequently alter insulin and glucagon secretion leading to dysglycemia. However, we know relatively little about the mechanisms influencing delta cells in health and disease. Thus, understanding factors that regulate delta cell SST secretion may reveal pathogenic mechanisms contributing to diabetes and direct new therapies to achieve glucose homeostasis. The satiety hormone leptin is known to suppress insulin and glucagon secretion from alpha and beta cells, respectively, but the mechanism is unclear. We demonstrate for the first time that leptin stimulates SST secretion from human and mouse islets, corresponding with decreased insulin and glucagon secretion. Our overarching hypothesis is that leptin stimulates delta cell SST secretion to inhibit alpha and beta cell function. This project aims to define the mechanisms of leptin action in delta cells and uncover a unifying mechanism whereby leptin acts indirectly on alpha and beta cells through paracrine SST signaling.


Project #2. Reduced beta cell mass underlies insulin deficiency leading to hyperglycemia in type 1 diabetes (T1D). Restoring autonomous glucose control in T1D requires beta cell replacement therapy, which is dependent on strategies to regenerate endogenous beta cells and expand islets ex vivo for transplant. However, there are no current therapeutic approaches to regenerate beta cells for people with T1D. To address this, we established a robust model of beta cell expansion through acute whole-body disruption of the leptin receptor (LepR). We found LepR deletion induces durable and remarkable beta cell expansion, even in ~2-year-old mice. Unbiased approaches nominated a candidate transcription factor (GABP) as a novel regulator of beta cell metabolism and proliferation. Studies in other cell types demonstrated GABP is required for mitochondrial biogenesis, oxidative phosphorylation, and cell cycle regulation; however, the function of GABP in beta cells is unknown. Our overarching hypothesis is that GABP couples expression of metabolism and cell cycle genes to promote beta cell proliferation. This project aims to uncover the mechanism of GABP directed beta cell proliferation in response to metabolic demand and will reveal new strategies to expand beta cells for people living with T1D.


Visit the PubMed profile page

  1. Ramirez Bustamante CE, Agarwal N, Cox AR, Hartig SM, Lake JE, Balasubramanyam A. “Adipose tissue dysfunction and energy balance paradigms in people living with HIV,” Endocrine Reviews, bnad028, August 2023. PMID: 37556371.
  2. Masschelin PM, Saha P, Ochsner SA, Cox AR, Kim KH, Felix JB, Sharp R, Li X, Tan L, Park JH, Wang L, Putluri V, Lorenzi PL, Nuotio-Antar AM, Sun Z, Kaipparettu BA, Putluri N, Moore DD, Summers SA, McKenna NJ, Hartig SM. “Vitamin B2 enables regulation of fasting glucose availability,” eLife, 12:e84077, July 2023. PMID: 37417957.
  3. Cox AR*, Masschelin PM, Saha PK, Felix JB, Sharp R, Lian Z, Xia Y, Chernis N, Bader DA, Kim KH, Li X, Yoshino J, Li X, Sun Z, Wu H, Coarfa C, Moore DD, Klein S, Sun K, Hartig SM*. “The Rheumatoid Arthritis Drug Auranofin Lowers Leptin Levels and Exerts Anti-Diabetic Effects in Obese Mice,” Cell Metabolism, 34(12):1932-1946.e7, Dec 2022. PMID: 36243005. *corresponding author
  4. He Y, Brouwers B, Liu H, Liu H, Lawler K, de Oliveira EM, Lee DK, Yang Y, Cox AR, Keogh J, Henning E, Bounds R, Perdikari A, Ayinampudi V, Wang C, Yu M, Tu L, Zhang N, Yin N, Han J, Scarcelli NA, Yan Z, Conde KM, Potts C, Bean JC, Wang M, Hartig SM, Liao L, Xu J, Barroso I, Mokrosinski J, Elmquist JK, Xu Y, Farooqi IS. “Human Loss-of-Function Variants in the Serotonin 2C Receptor Associated with Obesity and Maladaptive Behavior,” Nature Medicine, 28(12):2537-2546, Dec 2022. PMID: 36536256.
  5. Cox AR, Chernis N, Kim KH, Masschelin PM, Saha PK, Briley SM, Sharp R, Li X, Felix JB, Sun Z, Moore DD, Pangas SA, Hartig SM. Ube2i Deletion in Adipocytes Causes Lipoatrophy in Mice. Mol Metab, 48:101221, Jun 2021. PMID 33771728
  6. Felix JB, Cox AR, Hartig SM. Acetyl-CoA and Metabolite Fluxes Regulate White Adipose Tissue Expansion. Trends Endocrinol Metab, 32(5):320-32, May 2021. PMID 33712368
  7. Hartig SM, Cox AR. Paracrine Signaling in Islet Function and Survival. J Mol Med, 98(4):451-67, Apr 2020. PMID 32067063. *corresponding author
  8. Vonberg AD, Acevedo-Calado M, Cox AR, Pietropaolo SL, Gianani R, Lundy SK, Pietropaolo M. CD19+IgM+ Cells Demonstrate Enhanced Therapeutic Efficacy in Type 1 Diabetes Mellitus. JCI Insight, 3(23):e99860, Dec 2018. PMID 30518692
  9. Cox AR, Kushner JA. Area IV Knockout Reveals How Pdx1 is Regulated in Postnatal Beta Cell Development. Diabetes, 66(11):2738-2740, Nov 2017. PMID 29061659
  10. Cox AR, Lam CJ, Rankin MM, Rios JS, Chavez J, Bonnyman CW, King KB, Wells RA, Anthony D, Tu JX, Kim JJ, Li C, Kushner JA. Incretin Therapies Do Not Expand Beta-Cell Mass or Alter Pancreatic Histology in Young Male Mice. Endocrinology, 158 (6):1701-14, Jun 2017. PMID 28323942. *Top 3 articles of 2017
  11. Cox AR, Barrandon O, Cai EP, Rios JS, Chavez J, Bonnyman CW, Lam CJ, Yi P, Melton DA, Kushner JA. Resolving Discrepant Findings on ANGPTL8 in Beta-Cell Proliferation: A Collaborative Approach to Resolving the Betatrophin Controversy. PLoS One, 11(7):e0159276, Nov 2016. PMID 27410263
  12. Cox AR, Lam CJ, Rankin MM, King KA, Chen P, Martinez R, Li C, Kushner JA. Extreme Obesity Induces Massive Beta Cell Expansion in Mice through Self-Renewal and Does Not Alter the Beta Cell Lineage. Diabetologia, 59(6):1231-41, Jun 2016. PMID 27003683