Sushil Gopal Rane, Ph.D.

Senior Investigator

Integrative Cellular Metabolism Section, Diabetes, Endocrinology, & Obesity Branch

NIDDK

Research Topics

Research Goal

The overarching research goal of the Rane laboratory is to understand how growth and developmental processes of organs tasked with maintaining energy balance affects systemic glucose homeostasis. Observations will enable an integrated view of multi-organ communication that underlies normal glucose homeostasis, and its derangement in metabolic disease.

Current Research

Our research is based on the central paradigm that optimal cellular growth and developmental processes are integral to lifelong systemic glucose homeostasis. Energy balance is achieved via both unique and integrative actions of multiple organ systems, necessitating a harmonious interrelationship amongst diverse organs. Indeed, dysfunction in one or more organs disturbs this delicate homeostatic balance to initiate and propagate metabolic disease. Our research is focused on understanding the unique and integrated mechanisms that enable normal glucose homeostasis as well as those that disrupt this intricate regulation. We base our research hypotheses on two inter-related themes. First, we examine the cell-specific mechanisms that underlie normal glucose homeostasis. Second, we study how the various organs, via those unique cell types, communicate to achieve metabolic harmony. To this end, we employ advanced genetic tools and techniques to understand the organization of the interorgan network tasked with maintenance of glucose homeostasis.

Applying our Research

Diabetes and obesity are global epidemics. Disease progression involves multi-organ dysfunction; thus, our findings will set the stage to help better our collective understanding of disease pathogenesis, with the potential to aid in the development of rational therapies.

Need for Further Study

Diabetes is a multiorgan malady. An integrated molecular picture of multi-organ communication and collaboration is needed to enable a better view into diabetes pathogenesis.

Biography

Senior Investigator, NIDDK, NIH, 2012–Present
Investigator, NIDDK, NIH, 2006–2012
NCI Scholar, NCI, NIH, 2001–2006
Fellow, Bristol-Myers Squibb Pharmaceutical Research Institute, 1997–1999
Ph.D., Temple University School of Medicine, 1996

Selected Publications

Bahn YJ, Yadav H, Piaggi P, Abel BS, Gavrilova O, Springer DA, Papazoglou I, Zerfas PM, Skarulis MC, McPherron AC, Rane SG. CDK4-E2F3 signals enhance oxidative skeletal muscle fiber numbers and function to affect myogenesis and metabolism. J Clin Invest. 2023;133(13).
Papazoglou I, Lee JH, Cui Z, Li C, Fulgenzi G, Bahn YJ, Staniszewska-Goraczniak HM, Piñol RA, Hogue IB, Enquist LW, Krashes MJ, Rane SG. A distinct hypothalamus-to-β cell circuit modulates insulin secretion. Cell Metab. 2022;34(2):285-298.e7.
Wankhade UD, Lee JH, Dagur PK, Yadav H, Shen M, Chen W, Kulkarni AB, McCoy JP, Finkel T, Cypess AM, Rane SG. TGF-β receptor 1 regulates progenitors that promote browning of white fat. Mol Metab. 2018;16:160-171.
Kim SY, Lee JH, Merrins MJ, Gavrilova O, Bisteau X, Kaldis P, Satin LS, Rane SG. Loss of Cyclin-dependent Kinase 2 in the Pancreas Links Primary β-Cell Dysfunction to Progressive Depletion of β-Cell Mass and Diabetes. J Biol Chem. 2017;292(9):3841-3853.
Yadav H, Quijano C, Kamaraju AK, Gavrilova O, Malek R, Chen W, Zerfas P, Zhigang D, Wright EC, Stuelten C, Sun P, Lonning S, Skarulis M, Sumner AE, Finkel T, Rane SG. Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling. Cell Metab. 2011;14(1):67-79.