Tata Institute of Fundamental Research

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Ullas S Kolthur

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:

Fanibunda SE, Deb S, Maniyadath B, Tiwari P, Ghai U, Gupta S, Figueiredo D, Weisstaub N, Gingrich JA, Vaidya ADB, Kolthur-Seetharam U*, Vaidya V*. (2019). Serotonin regulates mitochondrial biogenesis and function in rodent cortical neurons via the 5-HT2A receptor and SIRT1-PGC-1α axis PNAS. 116(22):11028-1103 (* Co-corresponding)

Deota S, Rathnachalam S, Namrata K, Boob M, Fulzele A, Radhika S, Ganguli S, Balaji C, Kaypee S, Vishwakarma KK, Kundu TK, Bhandari R, Gonzalez de Peredo A, Mishra M, Venkataramani R*, Kolthur-Seetharam U* (2019). Allosteric Regulation of Cyclin-B Binding by the Charge State of Catalytic Lysine in CDK1 Is Essential for Cell Cycle Progression. J. Molecular Biology. pii: S0022-2836(19)30187-1. (* Co-corresponding).

Maniyadath B, Chattopadhyay T, Verma S, Kumari S, Kulkarni P, Banerjee K, Lazarus A, Kokane SS, Shetty T, Anamika K, Kolthur-Seetharam U* (2019). Loss of Hepatic Oscillatory Fed microRNAs Abrogates Refed Transition and Causes Liver Dysfunctions. Cell Reports 26(8):2212-2226.e7

Ravi V, Jain A, Khan D, Ahamed F, Mishra S, Giri M, Inbaraj M, Krishna S, Sarikhani M, Maity S, Kumar S, Shah RA, Dave P, Pandit AS, Rajendran R, Desingu PA, Varshney U, Das S, Kolthur-Seetharam U, Rajakumari S, Singh M, Sundaresan NR*. SIRT6 transcriptionally regulates global protein synthesis through transcription factor Sp1 independent of its deacetylase activity. Nucleic Acids Res. 2019 Aug 2. pii: gkz648. doi: 10.1093/nar/gkz648.

Parik S, Tewary S, Ayyub C, Kolthur-Seetharam U* (2018). Loss of mitochondrial SIRT4 shortens lifespan and leads to a decline in physical activity. J. Biosciences 43(2):243-247.

Khan D, Sarikhani M, Dasgupta S, Maniyadath B, Pandit AS, Mishra S, Ahamed F, Dubey A, Fathma N, Atreya HS, Kolthur-Seetharam U, Sundaresan NR* (2018). SIRT6 deacetylase transcriptionally regulates glucose metabolism in heart.. J Cell Physiol. doi: 10.1002/jcp.26434

Deota S, Chattopadhyay T, Ramachandran D, Armstrong E, Camacho B, Maniyadath B, Fulzele A, Gonzalez-de-Peredo A, Denu JM, Ullas Kolthur-Seetharam* (2017). Identification of a tissue-restricted isoform of SIRT1 defines a regulatory domain that encodes specificity. Cell Reports. 18(13):3069-3077

Banerjee K, Deshpande R, Koppula P, Ayyub P, Kolthur-Seetharam U* (2017). Central metabolic-sensing remotely controls nutrient-sensitive endocrine response in Drosophila via Sir2/Sirt1-upd2-IIS axis. J. Exp. Biol 220(Pt 7):1187-1191

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