Sushil Gopal Rane, Ph.D.
Regenerative Biology Section, Diabetes, Endocrinology, and Obesity Branch
Building 10-CRC, Room 5-5950
10 Center Dr
Bethesda, MD 20814
+1 301 873 4619
The overarching research goal is to understand the growth and development processes of various organ systems tasked with maintaining glucose tolerance and energy homeostasis. Findings will provide an integrated view of the multi-organ communication that underlies normal glucose homeostasis, and its derangement in metabolic disease.
Metabolic homeostasis is achieved via a concerted and integrative action of various organ systems, thus maintaining tight regulation of glucose levels. Dysfunction in one or more organ systems disturbs this homeostasis and propagates diabetes. Understanding the mechanisms that enforce glucose homeostasis and those that disrupt the tight regulation is thus of great medical significance. Our research over the past decade has been based on the central notion that the cell cycle network plays an integral role in maintenance of metabolic homeostasis and that mutations in cell cycle molecules contribute to metabolic dysfunction observed in diabetes and obesity. The abundance of cell cycle loci in genome-wide association studies of type 2 diabetes (T2D) lends credence to these hypotheses. We research two inter-related themes. First, we study the basic cellular processes that instruct development, growth and differentiation of metabolic organs. Second, we investigate the effects of mutations in key cell cycle molecules on the growth, development and function of these organs. Specifically, we are investigating the role of Cdks and the transforming growth factor-beta (TGF-ß) signaling pathway. Using tissue-specific conditional mouse models and primary cell culture-based systems, we aim to study the range of signals that determine growth, proliferation, differentiation, and apoptosis of cells that comprise the various metabolic tissues tasked with maintaining 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
The new information generated via genome-wide association studies of type 2 diabetes has offered many targets. These targets need to be validated by further experimentation. Moreover, type 2 diabetes pathogenesis cannot be fully explained by the findings of the genome-wide association studies, which is possibly due to small effects of multiple targets. An integrated molecular picture of multi-organ dysfunction will enable a better view into disease pathogenesis.
- 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
Lee JH, Mellado-Gil JM, Bahn YJ, Pathy SM, Zhang YE, Rane SG. Protection from β-cell apoptosis by inhibition of TGF-β/Smad3 signaling. Cell Death Dis. 2020;11(3):184.
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, Devalaraja S, Chung ST, Rane SG. TGF-β1/Smad3 Pathway Targets PP2A-AMPK-FoxO1 Signaling to Regulate Hepatic Gluconeogenesis. J Biol Chem. 2017;292(8):3420-3432.
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.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on February 9th, 2021