Mahadeb Pal, Ph.D. Associate Professor Division of Molecular Medicine Ph.D. (Biochemistry) Bose Institute, Calcutta University (1994) Tel: 91-33-2569-3256 Fax: 91-33-2355-3886 Email: mahadeb@boseinst.ernet.in palmahadeb@gmail.com

Area of interest:

1. Understanding the molecular mechanisms of rapid transcriptional activation of stress induced genes in mammalian cells.

2. Screening of Indian medicinal plant extracts for isolation of anti-cancer therapeutics with special interests in finding modulators of cellular
   i) Heat Shock Response pathway, and
   ii) Toll Like Receptor (TLR) signaling pathways

We are interested to study the molecular mechanisms of cancer development, growth and progression to be able to better intervene the processes as well as to isolate and design new and more effective anticancer agents from plant origin. Stress inducible pathways are critical in various cancers that are as such known to be activated in cells very rapidly under suitable stimuli. For mechanism studies, at present we aim to look at functions of two major cellular stress responsive transcription factors implicated in prosurvival phenotypes of cancer cells, Heat Shock Factor and NFkB which can activate target genes within minutes upon heat shock and proinflammatory stimuli, respectively. It is now apparent that most if not all rapidly induced cellular genes are regulated at the stage of promoter clearance; under an uninduced state these genes have transcriptionally engaged but promoter proximally paused RNA polymerase II (pol II) which translocates into elongation state upon receiving an activation signal. Therefore, one major aim in the lab is to have deeper insight into how a poised pol II is staged on a gene promoter, and is activated using biochemical approaches including chromatin immunoprecipitation (ChIP) based experiments.

India is a rich source of medicinal plants that have been used with reasonable success for treatment of various ailments for ages in Ayurveda; however, by principle these treatments often are not very efficient. Another major aim in the lab is to screen medicinal plant extracts by highly sensitive- and custom designed cell based assay systems for identifying molecules that modulate a specific cellular activity. We are interested in isolating molecules/activities that support cellular growth, proliferation, anti-proliferation to find, and eventually design more efficient anticancer agents. We have great interests as well in activities that would act as an agonist or antagonist of a specific TLR. TLRs have been implicated in infection, inflammation, radioprotection etc in animals. New activities/molecules thus obtained will eventually be used as tools to have deeper insights into the mechanisms of various aspects of cancer, and other relevant cellular phenotypes.

 Collaborators:

Dr. Andrei Gudkov, Roswell Park Cancer Institute, Buffalo, New York

Dr. Katerina Gurova, Roswell Park Cancer Institute, Buffalo, New York

Selected Publications   

1.  Gasparian, A.V., Burkhart, C. A., Purmal, A. A., Brodsky,  L. Pal, M, Saranadasa, M., Bosykh, D. A., Commane, M.., Guryanova, O. A., Pal, S, Safina, A., Svirido, S., Koman, I. E, Veith, J., Komar, A., A,  Gudkov, A. V, Gurova, K. V. (2011) Curaxins: anticancer compounds that simultaneously suppress NF-κB and activate p53 by targeting FACT. Science Translational Medicine. 3, 95ra74

2.  Újvári Andrea, Pal Mahadeb, Luse Donal (2011) The functions of TFIIF during initiation and transcript elongation are differentially affected by phosphorylation by casein kinase 2. Journal of Biological Chemistry 286, 23160-7

3.  Pavel Čabart, Andrea Újvári, Mahadeb Pal and Donal S. Luse (2011) TFIIF is not required for initiation by RNA polymerase II but it is essential to stabilize TFIIB in early transcription complexes, Proceeding of the National Academy of Sciences (USA), 108(38):15786-91

4. Mahadeb Pal, Alfred S. Ponticelli and Donal Luse (2005) The role of the transcription bubble and TFIIB in promoter clearance by RNA polymerase II Molecular Cell, 19, 101-110

5. Mahadeb Pal and Donal Luse (2003) The transition from initiation to elongation: lateral mobility of the RNA-DNA hybrid in human RNA polymerase II complexes is greatly reduced at +8/+9 and absent by +23. Proceeding of the National Academy of Sciences (USA), 100, 5700-5705

6.  Ujvari, A., Mahadeb Pal and Donal Luse (2002) RNA polymerase II transcription complexes become arrested if the nascent RNA is shortened to less than 50 nucleotides. Journal of Biological Chemistry, 277, 32527-32537

7. Mahadeb Pal and Donal S. Luse (2002) Strong natural pausing by RNA polymerase II within 10 bases of transcription start may result in repeated slippage and re-extension of the nascent RNA Molecular and Cellular Biology,  22, 30-40 

8*. Mahadeb Pal, David McKean and Donal S. Luse (2001) Promoter clearance by RNA polymerase II is an extended, multi-step process strongly influenced by sequence. Molecular and Cellular Biology, 21, 5815-5825

9.  Mahadeb Pal, Yasuhito Ishigaki, Eszter Nagy, and L. E.  Maquat (2001) Evidence that phosphorylation of human Upf1 protein varies with intracellular location and is mediated by a wortmannin-sensitive and rapamycin-sensitive PI 3-kinase-related kinase signaling pathway. RNA, 7, 5-15