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  Lab Location: #3-17

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  Key Publications  

Ghosh A, Saginc G, Leow SC, Khattar E, Shin EM, Yan TD, Wong M, Zhang Z, Li G, Sung WK, Zhou J, Chng WJ, Li S, Liu E, Tergaonkar V. (2012)
Telomerase directly regulates NF-κB-dependent transcription.
Nature Cell Biology (article) 2012 Dec;14(12):1270-81. doi: 10.1038/ncb2621. Epub 2012 Nov 18.

Zhao-Hui Wu, Ee Tsin Wong, Yuling Shi, Zhijian Chen, Shigeki Miyamoto and Vinay Tergaonkar. (2010).
ATM-dependent ELKS ubiquitination coordinates IKK activation in response to genotoxic stress.
Molecular Cell.
40(1): 75-86.

Hsiangling Teo, Sourav Ghosh , Hendrik Luesch , Ee Tsin Wong, Arkasubhra Ghosh, Najib Malik, Anthony Orth, Paul de Jesus, Anthony S Perry, Jeffrey D. Oliver, Nhan L. Tran, Lisa J. Speiser, Enrique Saez,  Peter Schultz, Sumit Chanda, Inder M Verma and Vinay Tergaonkar. (2010).
Telomere independent Rap1 is an IKK-adaptor and regulates NFkB- dependent gene expression.
Nature Cell Biology (article) 12(8): 758-67.

Chew J, Biswas S, Shreeram S, Humaidi M, Wong ET, Dhillion MK, Teo H, Hazra A, Fang CC, López-Collazo E, Bulavin DV, Tergaonkar V. (2009).
WIP1 phosphatase is a negative regulator of NF-kappaB signalling.
Nature Cell Biology.
11(5), 659-66.

Xia Y, Padre RC, De Mendoza TH, Bottero V, Tergaonkar VB*, Verma IM. (2009).
Phosphorylation of p53 by IkappaB kinase 2 promotes its degradation by beta-TrCP.
Proc Natl Acad Sci U S A. 106(8), 2629-34. * Corresponding Author

Dey A, Tergaonkar V*, Lane DP. (2008).
Double-edged swords as cancer therapeutics: simultaneously targeting p53 and NF-kappaB pathways.
Nature Reviews Drug Discovery.
7(12), 1031-40. * Corresponding Author

Vince JE, Wong WW, Khan N, Feltham R, Chau D, Ahmed AU, Benetatos CA, Chunduru SK, Condon SM, McKinlay M, Brink R, Leverkus M, Tergaonkar V, Schneider P, Callus BA, Koentgen F, Vaux DL, Silke J. (2007).
IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis.
Cell. 131(4), 682-93.

Dey A, Wong ET, Cheok CF, Tergaonkar V*, Lane DP. (2008).
R-Roscovitine simultaneously targets both the p53 and NF-kappaB pathways and causes potentiation of apoptosis: implications in cancer therapy.
Cell Death Differ. 15(2), 263-73. *Corresponding Author

Biswas SK, Bist P, Dhillon MK, Kajiji T, Del Fresno C, Yamamoto M, Lopez-Collazo E, Akira S, Tergaonkar V. (2007).
Role for MyD88-independent, TRIF pathway in lipid A/TLR4-induced endotoxin tolerance.
Journal of Immunology. 179(6), 4083-92. IF:6

Tergaonkar V*, Perkins ND. (2007).
p53 and NF-kappaB crosstalk: IKKalpha tips the balance.
Molecular Cell.
26(2), 158-9. *Corresponding author. IF:14

Basak S, Kim H, Kearns JD, Tergaonkar V, O'Dea E, Werner SL, Benedict CA, Ware CF, Ghosh G, Verma IM, Hoffmann A. (2007).
A fourth IkappaB protein within the NF-kappaB signaling module.
128(2), 369-81.

Ghosh S, Tergaonkar V*, Rothlin CV, Correa RG, Bottero V, Bist P, Verma IM, Hunter T. (2006).
Essential role of tuberous sclerosis genes TSC1 and TSC2 in NF-kappaB activation and cell survival.
Cancer Cell. 10(3), 215-26. *Co-first author

Tergaonkar, V., Correa, R.G., Ikawa, M. and Verma, I.M. (2005).
Distinct roles of IkappaB proteins in regulating constitutive NF-kappaB activity.
Nature Cell Biology. 7, 921-923.

Tergaonkar, V., Pando, M., Vafa, O., Wahl, G. and Verma I.M. (2002).
p53 stabilization is decreased upon NFkB activation: a role for NFkB in acquisition of resistance to chemotherapy.
Cancer Cell. 1, 493-503.


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Vinay Tergaonkar obtained his Ph.D. (2001), from National Center for Biological Sciences, Bangalore. During his graduate studies he was awarded an international cancer society (UICC) fellowship for collaborative research at Tufts University, Boston, USA. He has been a fellow (2001-2004) and a special fellow (2004-present) of the Leukemia and Lymphoma Society of America and conducted his postdoctoral studies at the Salk Institute for Biological Studies, La Jolla, California. He joined IMCB in late 2005 as Principal Investigator (Assistant professor) and became a Senior Principal Investigator (Associate professor) in 2010 and Research Director (Professor) in 2015.

He holds adjunct appointments at 1) Department of Biochemistry (NUS) 2) Cancer Science Institute, and 3) Singapore Eye Research Institute. He has been invited to speak at various international venues and meetings such as the Barossa and Hunter valley meetings in Australia, Genes and Cancer meeting in UK, The Argentine Pharmacological society meeting in Buenos Aires, Aichi and Japanese Cancer Society meetings in Japan and the Keystone Symposia. He serves on Editorial Boards of 1) Biochemical Journal (Portland Press) 2) Critical Reviews in Oncology/Hematology (Elsevier Press), 3) BMC Research Notes (Biomed Central) and 4) Telomeres and Telomerase. He has received international recognition for his work including the British council development award (2014) and the Premiers’ fellowship from Government of South Australia (2015) for outstanding contribution to the field.

    Deregulated activity of the transcription factor NFkB

It is causally linked to the development of several human ailments including cancers. Deciphering the regulation of NFkB function is crucial to understanding the mechanism and role of constitutive NFkB activity seen in human malignancies. Dr Tergaonkar's group has demonstrated that NFkB mitigates the function of the tumor suppressor protein p53, thereby promoting resistance to chemotherapy induced apoptosis. Thus blocking NFkB could be used as an adjuvant to existing chemotherapy regimens. Consistent with their data, NFkB inhibitors are showing promising results in clinical trials. Uncovering the mechanism of NFkB mediated resistance to physiologically relevant apoptotic stimuli is one of the group's goals.

Given that over 200 physiological stimuli activate NFkB, which in turn regulates an equally large number of genes, understanding how specificity is generated in such a pleiotropic pathway is also a major challenge. Using a large-scale functional genomics approach, parallel interrogation of approximately 20,000 sequence-annotated genes was carried out and several novel modifiers of NFkB activity were identified. The group aims to characterize these proteins and the mechanisms by which they regulate NFkB.

A bottleneck in studying mammalian signaling lies in the ability to deliver genes/siRNAs to the desired cell types and also be able to turn these genes on or off at will. Recently, Dr. Tergaonkar has used lentiviruses, which can infect dividing and non-dividing cells of virtually any lineage, to generate transgenic mice with regulated expression or knock down of genes of interest. The lentiviral transgenesis approach can also be used for delineating functional domains/regulatory sites of a given protein in vivo and for generating human disease models. The group plans to analyze the candidates obtained in their genome wide screen using such approaches.

In resting cells, NFkB is bound to the IkB family of inhibitors. Degradation of IkB proteins in response to stimuli and subsequent covalent modifications of NFkB are essential for gene activation. Using mouse models, the group plans to investigate the modifications of NFkB that are critical for its role in development, inflammation and tumorigenesis. As a complementary approach, they will study cell lines and biopsies from human patients, to investigate the role of certain kinases, ubiquitin ligases and other modifying enzymes that might contribute towards deregulated NFkB activity in diseases.