In this proposal we will use mouse models that have mutations in the Cdk4 locus. Cdk4-/- mice are diabetic and lean, and in contrast, Cdk4R24C mice are non-diabetic and heavier. These observations are consistent with the documented, albeit not very well characterized, role of the RB/E2F pathway in adipogenesis amd muscle differentiation. Since Cdk4 is an upstream regulator of the E2F-RB pathway, we hypothesize that Cdk4 activity may regulate adipogenesis and muscle development and function. Further, the effect of Cdk4 on production of insulin, sex hormones and glucose regulation may impact the energy balance in the Cdk4R24C model. We are studying mechanisms of glucose tolerance and energy homeostasis by evaluating CDk4-dependent functions in different metabolic organs in the Cdk4 mice. The findings are revealing important role of Cdk4 in process that modulate energy balance.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Kim, So Yoon; Lee, Ji-Hyeon; Merrins, Matthew J et al. (2017) Loss of Cyclin-dependent Kinase 2 in the Pancreas Links Primary ?-Cell Dysfunction to Progressive Depletion of ?-Cell Mass and Diabetes. J Biol Chem 292:3841-3853
Wankhade, Umesh D; Rane, Sushil G (2017) Flow Cytometry Assisted Isolation of Adipose Tissue Derived Stem Cells. Methods Mol Biol 1566:17-24
Tiano, Joseph P; Springer, Danielle A; Rane, Sushil G (2015) SMAD3 negatively regulates serum irisin and skeletal muscle FNDC5 and peroxisome proliferator-activated receptor ? coactivator 1-? (PGC-1?) during exercise. J Biol Chem 290:7671-84
Tarbell, Kristin V; Rane, Sushil G (2015) Saving ? cell function in the NIK of time. J Exp Med 212:1140-1
Yadav, Hariom; Rane, Sushil G (2015) Dietary fatty acids: Friends or foes? Obesity (Silver Spring) 23:1329
Fernandez, Patricia; Scaffidi, Paola; Markert, Elke et al. (2014) Transformation resistance in a premature aging disorder identifies a tumor-protective function of BRD4. Cell Rep 9:248-60
Yadav, Hariom; Lee, Ji-Hyeon; Lloyd, John et al. (2013) Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1 Hormone Secretion. J Biol Chem 288:25088-97
Jiao, W; Lin, H-M; Datta, J et al. (2008) Aberrant nucleocytoplasmic localization of the retinoblastoma tumor suppressor protein in human cancer correlates with moderate/poor tumor differentiation. Oncogene 27:3156-64