Shazib Pervaiz

Educational Background: MBBS, Ph.D.

Position: Professor

Contact number/s: 6516 6602(Office); 6516 3229(Lab)

Email address: phssp@nus.edu.sg, Shazib_Pervaiz@nuhs.edu.sg

Location of Office: MD9, Level 4

Location of Laboratory: MD9, Level 2

Name of Laboratory: ROS Biology & Apoptosis Lab

Other Affiliations::

• NUS Graduate School for Integrative Sciences and Engineering
• National University Cancer Science Institute, NUHS

Fellowships:

• Department of Pathology, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA
• Cancer Center, Massachusetts General Hospital, Charlestown, MA, USA
• Millennium Pharmaceuticals Inc., Cambridge, MA, USA

Research Synopsis

The primary focus of our laboratory over the years has been in deciphering signaling networks that promote cellular transformation and elucidating mechanisms that endow cancer cells the ability to evade execution. Our focus has been on identifying potential bottlenecks or vulnerabilities that cut across a spectrum of human cancers, and therefore our work includes hematopoietic malignancies as well as solid tumors, in particular, breast, colorectal, lung and pancreatic cancer. To that end, using a variety of model systems such as oncogene-induced proliferation, expression of apoptosis inhibitory proteins, pharmacological inhibition of key cellular metabolic regulators, receptor and chemotherapy-induced death stimuli, and novel small molecule compounds, we provide evidence that cellular redox metabolism critically impacts cell fate decisions. Of note, across a wide spectrum of cellular redox stress, there emerges a dichotomy of responses in terms of cell survival/proliferation and cell death. At the lower end of the scale cell survival and proliferation is favored, while at the other extreme cell execution is the preferred outcome. How these varied levels of stress evoke disparate biological responses with distinct functional outcome(s) and the signaling networks and potential cellular targets that could be amenable to redox modification(s) are the major focus of our ongoing and future investigations

Research Areas of Interest:

• Regulation of Cell Death Signaling in Cancer Cells
• Reactive Oxygen Species and Cell Fate
• Bcl-2 Family and Mitochondrial Metabolism
• Protein Phosphatase PP2A and Cancer
• Autophagy and Cancer
• Experimental Therapeutics

Selected Publications

• Clement, M-V., Hirpara, J., Chowdhury, S., and Pervaiz, S. Chemopreventive agent resveratrol, a natural product derived from grapes, triggers CD95-signaling dependent apoptosis in human tumor cells. Blood, 92(3):996-1002, 1998.
• Hirpara, J.L., Seyed, M.A., Dong, H., Kini, M., and Pervaiz, S. Induction of mitochondrial permeability transition and cytochrome C release in the absence of caspase activation is insufficient for effective apoptosis in human leukemia cells. Blood, 95(5):1773-80, 2000.
• Pervaiz, S., Cao, J., Chao, O. S. P., Chin, Y. Y., and Clément, M-V. Activation of the Rac GTPase inhibits apoptosis in human tumor cells. Oncogene, 20(43):6263-68, 2001.
• Clement, M-V., Hirpara, J.L., and Pervaiz, S. Decrease in intracellular superoxide sensitizes Bcl-2 overexpressing tumor cells to receptor- and drug-induced apoptosis independent of the mitochondria. Cell Death Diff. 10(11):1273-85, 2003.
• Chen, Z, X. and Pervaiz, S. Bcl-2 induces pro-oxidant state by engaging mitochondrial respiration in tumor cells. Cell Death Diff. 14(9): 1617-27, 2007.
• Poh TW, Huang S, Hirpara JL, and Pervaiz S. LY303511 amplifies TRAIL-induced apoptosis in tumor cells by enhancing DR5 oligomerization, DISC assembly, and mitochondrial permeabilization. Cell Death Diff. 14(10): 1813-25, 2007.
• Kumar AP, Quake AL, Chang MK, Zhou T, Lim KS, Singh R, Hewitt RE, Salto-Tellez M, Pervaiz S, Clément MV. Repression of NHE1 expression by PPARgamma activation is a potential new approach for specific inhibition of the growth of tumor cells in vitro and in vivo. Cancer Research 15;69(22):8636-44, 2009.
• Chen ZX, and Pervaiz S. Involvement of cytochrome c oxidase subunits Va and Vb in the regulation of cancer cell metabolism by Bcl-2. Cell Death Differ. 17(3):408-20, 2010.
• Indran IR, Hande MP, Pervaiz S. hTERT overexpression alleviates intracellular ROS production, improves mitochondrial function, and inhibits ROS-mediated apoptosis in cancer cells. Cancer Research. 1;71(1):266-76, 2011. (Discussed in highlights in cancer literature under breaking advances. Cancer Research, 71, 1-2, 2011).
• Velaithan R, Kang J, Hirpara JL, Loh T, Goh BC, Le Bras M, Brenner C, Clement MV, and Pervaiz S. The small GTPase Rac1 is a novel binding partner of Bcl-2 and stabilizes its antiapoptotic activity. Blood. 9;117(23):6214-26, 2011.
• Zhu Y, Casey PJ, Kumar AP, Pervaiz S. Deciphering the signaling networks underlying simvastatin-induced apoptosis in human cancer cells: evidence for non-canonical activation of RhoA and Rac1 GTPases. Cell Death Disease. 4:e568. doi: 10.1038/cddis.2013.103, 2013.
• Kumar AP, Loo SY, Shin SW, Tan TZ, Eng CB, Singh R, Putti TC, Ong CW, Salto-Tellez M, Goh BC, Park JI, Thiery JP, Pervaiz S*, Clement MV*. Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast cancer. Antioxid. Redox Signal, 20(15):2326-46, 2014 (*joint senior author).
• Low IC, Loh T, Huang Y, Virshup DM, and Pervaiz S. Sustained Ser70 phosphorylation of Bcl-2 by selective tyrosine nitration of PP2A-B56δ stabilizes its antiapoptotic activity. Blood, 124(14):2223-34, 2014. (*Commentary by S. Nakahata and K. Morishita in the same issue).
• Kang J, Chong SJ, Ooi VZ, Vali S, Kumar A, Kapoor S, Abbasi T, Hirpara JL, Loh T, Goh BC, and Pervaiz S. Overexpression of Bcl-2 induces STAT-3 activation via an increase in mitochondrial superoxide. Oncotarget. Oct 27; 6(33):34191-205, 2015 .
• Iskandar K, Rezlan M, Yadav S, Foo Chuan Han J, Sethi G, Qiang Y, Bellot G, and Pervaiz S. Synthetic lethality of a novel small molecule against mutant KRAS expressing cancer cells involves AKT-dependent ROS production. Antioxid. Redox Signal. 10;24(14):781-94, 2016.

Books Edited:
Mitochondria: The anti-cancer target for the third millennium. 2014 (Editors: Jiri Neuzil, Shazib Pervaiz and Simone Fulda). Publisher: Springer

Awards