Ullas S Kolthur
Sirtuins: implications in cancer and aging
Biochemistry, Biophysics, Molecular Biology
Metabolic and energy homeostasis play a vital role in governing the cellular pathways. It is important to note that molecular factors involved in these processes are implicated in life-style disorders (diabetes/ obesity), aging and age related diseases (cancer/ neurodegeneration).
One of the proteins that directly link metabolic inputs to various molecular events within a cell is Sir2, which was initially identified in yeast as an NAD-dependent HDAC. Sirutins (Sir2-like proteins) play a vital role in cell survival, DNA damage response, cellular differentiation and aging. We use flies, mice and cell culture systems to elucidate the molecular mechanisms regulated by sirtuins. Importantly, we investigate their functions in metabolic and energy homeostasis and also study their role during aging and age-related diseases such as cancer, diabetes and obesity.
1. Banerjee KK, Ayyub C, Sengupta S, Kolthur-Seetharam U (2013) Fatbody dSir2 regulates muscle mitochondrial physiology and energy homeostasis via fat metabolism and IIS, and mimics the autonomous functions of dSir2 in muscles. Molecular and Cellular Biology 33: 252
2. Lazarus A, Banerjee KK, Kolthur-Seetharam U (2013). Small Changes, Big Effects: Chromatin Goes Aging. Subcellular Biochemistry 61:151
3. Banerjee K, Ayyub C, Ali SZ, Mandot V, Prasad NG, Kolthur-Seetharam U (2013) dSir2 in the adult fatbody but not muscles regulates lifespan in a diet-dependent manner. Cell Reports 2: 1485.
4. Banerjee K, Ayyub C, Sengupta S, Kolthur-Seetharam U (2012) dSir2 deficiency in the fatbody, but not muscles, affects systemic insulin signaling, fat mobilization and starvation survival in flies. Aging 4:206
5. Ramachandran D, Roy U, Ghosh S, Garg S, Pathak S, Kolthur-Seetharam U (2011) Glucose dependent changes in mir-9 transcription regulate the NAD-dependent deacetylase Sirt1 in insulin secreting beta-cells. FEBS Journal 278(7):1167