Sushil G. Rane, Ph.D.
- 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
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.
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.
- A distinct hypothalamus-to-β cell circuit modulates insulin secretion.
- 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.
- Cell Metab (2022 Feb 1) 34:285-298.e7. Abstract/Full Text
- TGF-β receptor 1 regulates progenitors that promote browning of white fat.
- Wankhade UD, Lee JH, Dagur PK, Yadav H, Shen M, Chen W, Kulkarni AB, McCoy JP, Finkel T, Cypess AM, Rane SG.
- Mol Metab (2018 Oct) 16:160-171. Abstract/Full Text
Research in Plain Language
Glucose is the main sugar that passes through the gut and into the bloodstream. When an individual has blood glucose (blood sugar) levels that are above the normal range, they are at risk for or have diabetes. Multiple organs perform unique as well as inter-dependent roles to help maintain normal blood glucose levels. This tight regulation is referred to as glucose homeostasis.
The pancreas organ houses islands of cells (called islets) that produce the hormones insulin and glucagon. Glucagon is produced by alpha cells and insulin is produced by beta cells of the islets. Insulin lowers blood glucose levels, whereas glucagon increases levels of glucose. Other organs such as the skeletal muscle, liver and adipose (fat) also play important roles in glucose homeostasis. The brain is the master controller of blood glucose levels by virtue of its ability to regulate what we eat, how often we eat, and how much we eat.
In summary, the various organs communicate and collaborate to maintain normal blood glucose levels in the body. Abnormal function of any one or more of the above-mentioned organs can disturb normal glucose homeostasis and cause or promote metabolic diseases such as diabetes and obesity.
We investigate how the proper development of various bodily organs allows us to maintain normal glucose levels. At the same time, we inquire how abnormal growth and development of those organs increases the likelihood of development of obesity and diabetes.
Gaining this knowledge will allow us to (1) better understand how our body works, (2) enable a greater understanding of disease development, and (3) allow design and development of potential treatments. To conduct these studies, we use appropriate mouse models and cells obtained from various organs, including human tissues and cell specimens.