Tata Institute of Fundamental Research

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Ullas S Kolthur

Associate Professor

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.

 

Selected Publications:

Deota S, Chattopadhyay T, Ramachandran D, Armstrong E, Camacho B, Maniyadath B, Fulzele A, Gonzalez-de-Peredo A, Denu JM, Kolthur-Seetharam U. Identification of a Tissue-Restricted Isoform of SIRT1 Defines a Regulatory Domain that Encodes Specificity. Cell Rep. 2017 Mar 28;18(13):3069-3077. doi: 10.1016/j.celrep.2017.03.012. PubMed PMID: 28355560; PubMed Central PMCID:PMC5545126.

Banerjee KK, Deshpande RS, Koppula P, Ayyub C, Kolthur-Seetharam U. Central metabolic sensing remotely controls nutrient-sensitive endocrine response in Drosophila via Sir2/Sirt1-upd2-IIS axis. J Exp Biol. 2017 Apr 1;220(Pt 7):1187-1191. doi: 10.1242/jeb.150805. Epub 2017 Jan 19. PubMed PMID: 28104798.

Muralidharan B, Khatri Z, Maheshwari U, Gupta R, Roy B, Pradhan SJ, Karmodiya K, Padmanabhan H, Shetty AS, Balaji C, Kolthur-Seetharam U, Macklis JD, Galande S, Tole S. LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11. J Neurosci. 2017 Jan 4;37(1):194-203. doi: 10.1523/JNEUROSCI.2836-16.2016. PubMed PMID: 28053041; PubMed Central PMCID:PMC5214630.

Ghosh S, Banerjee KK, Vaidya VA, Kolthur-Seetharam U. Early Stress History Alters Serum Insulin-Like Growth Factor-1 and Impairs Muscle Mitochondrial Function in Adult Male Rats. J Neuroendocrinol. 2016 Sep;28(9). doi: 10.1111/jne.12397. PubMed PMID: 27196416.

Sehgal L, Mukhopadhyay A, Rajan A, Khapare N, Sawant M, Vishal SS, Bhatt K, Ambatipudi S, Antao N, Alam H, Gurjar M, Basu S, Mathur R, Borde L, Hosing AS, Vaidya MM, Thorat R, Samaniego F, Kolthur-Seetharam U, Dalal SN. 14-3-3γ-Mediated transport of plakoglobin to the cell border is required for the initiation of desmosome assembly in vitro and in vivo. J Cell Sci. 2014 May 15;127(Pt 10):2174-88. doi: 10.1242/jcs.125807. Epub 2014 Mar 7. PubMed PMID: 24610948.

Ho L, Titus AS, Banerjee KK, George S, Lin W, Deota S, Saha AK, Nakamura K, Gut P, Verdin E*, Kolthur-Seetharam U*. (2013) SIRT4 regulates ATP homeostasis and mediates a retrograde signaling via AMPK. Aging.  5(11):835-49

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. Mol Cell Biol. 33(2):252-64

Banerjee KK, Ayyub C, Ali SZ Mandot V, Prasad NG, Kolthur-Seetharam U (2012) dSir2 in the fatbody but not muscles regulates diet-dependent lifespan extension. Cell Reports (Cell Press) 2(6):1485-91 {The article was previewed in the same issue by Eric Verdin and David Sinclair]

Pubmed: Ullas Kolthur-Seetharam
Pubmed: Kolthur US
Pubmed: Ullas KS

 

Awards: Swarnajayanti Award/Fellow, DST-India


Contact

  • Room B-306
  • Tel: +91 22 2278 2721
  • ullas @ tifr.res.in
  • Webpage