Sudhakar JHA

Down-regulation of tumor suppressors or expression of oncogenes is a hallmark feature of cancers. These alterations in the transcriptome arise as a consequence of a malfunction in the chromatin organization. Chromatin remodeling complexes play an important role in maintaining this organization as they create a histone code that is read by specific readers resulting in an active or repressed chromatin. Dr Jha is interested in studying the regulation of chromatin remodeling complexes and their role in cancer prevention.

csisjha@nus.edu.sg

Biosketch

Principal Investigator, Cancer Science Institute of Singapore, NUS
Assistant Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS

Year(s) Degree (if applicable) Institute
1998 BSc Ewing Christian College, Allahabad University, Allahabad, India
2000 Master of Science School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
2003 PhD School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
2011 – Present Principal Investigator, Cancer Science Institute of Singapore, National University of Singapore
2003 – 2011 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, USA

Research

Chromatin remodeling complexes play an important role in maintaining chromatin organization as they create a histone code that is read by specific readers resulting in an active or repressed chromatin. We are interested in understanding the regulation of chromatin remodeling complexes and their role in cancer prevention and intervention. We have purified and characterized chromatin remodeling complexes implicated in transcription and DNA damage response(Mol Cell 2009, 34: 521-533). We have identified the role of TIP60, a histone acetyltransferase in DNA damage response pathway (Mol Cell Biol 2008, 28: 2690-2700) and RVB1, a component of TIP60 complexes to be required for activity of this complex (Mol Cell Biol 2013, 33: 1164-74). In addition to purifying and characterizing these chromatin-remodeling complexes, we have also identified viral and cellular regulators of TIP60, a tumor suppressor. We have discovered viral oncogenes such as, Human Papillomavirus (HPV) E6 and Adenovirus (AdV) to destabilize TIP60 (Mol Cell 2010, 38: 700-711 and Oncogene 2013, 32: 5017-25) and also discovered an oncogenic mircoRNA (miR-22) to target mRNA of TIP60 (Oncotarget 2015, in press). Furthermore, we have identified the mechanism of TIP60 destabilization by E6, and its implications in cervical cancer progression (Oncogene 2015, in press). Currently, in the absence of an effective therapeutic vaccine, cervical cancer still remains to be a major disease burden. Hence, our group is focusing on investigating the role of TIP60 in cervical cancer progression as we have shown that reactivation of TIP60 could be of therapeutic value.

Lab Members

Selected Publications

1. Jadhav S, Kumari N, Ng L, Tan PF, Yeo-The NSL, Tian JS, Koh BTH, Chan MC, Wong W, Chng WJ, Fullwood MJ, Guccione E, Karnani N, Tenen DG and Jha S. 1. circASXL1-1 regulates BAP1 deubiquitinase activity in leukemia. Haematologica, 2019, in press.

2. Rajagopalan D, Magallanes RT, Bhatia SS, Sian S, Hora S, Lee KK, Zhang Y, Jadhav SP, Wu Y, Gan Y, Karnani N, Benoukraf T and Jha S. TIP60 represses activation of endogenous retroviral elements. Nucleic Acids Res, 2018 Oct 12;46(18):9456-9470.

3. Teh NSL, Ito Y, Jha S. High-Risk Human Papillomaviral Oncogenes E6 and E7 Target Key Cellular Pathways to Achieve Oncogenesis. Genes Dev. 2018 Jun 8;19(6). pii: E1706

4. Rajagopalan D and Jha S. 4. An epi(c)genetic war: Pathogens, Cancer and the Human Genome BBA Reviews on Cancer. 2018 Apr;1869(2):333-345.

5.Rajagopalan D, Pandey AK, Xiuzhen MC, Lee KK, Hora S, Zhang Y, Chua BH, Kwok HS, Bhatia SS, Deng LW, Tenen DG, Kappei D and Jha S.TIP60 represses telomerase expression by inhibiting Sp1 binding to the TERT promoter. PLoS Pathog.,2017 Oct 18;13(10): e1006681.

6. Zhang Y, Subbaiah VK, Rajagopalan D, Tham CY, Abdullah LN, Toh TB, Gong M, Tan TZ, Jadhav SP, Pandey AK, Karnani N, Chow EK, Thiery JP and Jha S. TIP60 inhibits metastasis by ablating DNMT1-Snail2 driven epithelial-mesenchymal transition program. Mol Cell Biol.2016 Oct; 8(5), 384–399.  Editorial highlight: “New factors involved in tumorigenesis”.

7. Subbaiah VK, Zhang Y, Rajagopalan D, Abdullah LN, Yeo-Teh NS, Tomai? V, Banks L, Myers MP, Chow EK, Jha S. E3 ligase EDD1/UBR5 is utilized by the HPV E6 oncogene to destabilize tumor suppressor TIP60. Oncogene.,2016 Apr 21;35(16):2062-74

8. Pandey AK, Zhang Y, Zhang S, Li Y, Tucker-Kellogg G, Yang H, Jha S. 8. TIP60-miR-22 axis as a prognostic marker of breast cancer progression. Oncotarget. 2015 Dec 1;6(38):41290-306.

9. Jha S, Vande Pol S, Banerjee NS, Dutta AB, Chow LT, Dutta A. Destabilization of TIP60 by human papillomavirus E6 results in attenuation of TIP60-dependent transcriptional regulation and apoptotic pathway. Mol Cell., 2010 Jun 11;38(5):700-11. Highlight: “Faculty of 1000 Biology”, 17th June 2010 

10. Jha S, Dutta A. Mol. RVB1/RVB2: running rings around molecular biology.,Mol Cell.,2009 Jun 12;34(5):521-33.