Biology Department Biology Department  

Mamta Naidu

Brookhaven National Laboratory - Past Employee

Currently at:
Department of Pharmacology
Basic Science Tower
Level 8, Room 140
Stony Brook University
Stony Brook, NY 11794-8651

Phone: (631) 444-3050
Fax: (631) 444-9749
email: mnaidu@pharm.stonybrook.edu


Past Research Interests

A)  Increased radio sensitization of glioma cell lines by lucanthone (and its structural analogue hycanthone) due to direct physical destabilization of DNA base excision repair enzyme Apurinic endonuclease1 (Ape1).
I am studying the dose response of glioma cell lines to low LET radiation in terms of DNA damage repair and ATP release, in order to determine if there is any correlation between DNA damage repair, radio-resistance and synaptic activity of these glioma cell lines. In this work, our experimental objective has been to determine the effect of low LET radiation on base excision repair enzyme, Apurinic Endonuclease-1 (Ape1) in glioma cell lines in presence of lucanthone, an anti-cancer drug (in phase II clinical trials) used to treat brain tumors in conjunction with radiotherapy. In this study I find that Ape1 endonuclease activity decreases in presence of lucanthone and this decrease can be correlated to decreased clonogenic survival of glioma cell lines. Interestingly, I find decreased Ape1 activity in glioma cell lines' cell extracts treated with increasing concentration of lucanthone in presence of protease inhibitor cocktail, indicative of lucanthone's degradative effects on Ape1. My collaboration with Rakhi Agarwal of Structural Biology group at BNL has yielded an Ape1 structure with an unknown hydrophobic site where lucanthone can possibly dock. Currently molecular docking/ dynamics studies are in progress for Ape1-lucanthone interaction. We have also established that Ape1 over expression in radiosensitive glioma cell line increases its radioresistance. In addition to these studies, Ape1 siRNA inhibition studies are in progress.

B)  Effect of low and high LET radiation on Apurinic Endonuclease-1 (Ape1) activity in glial progenitor cells.
It is crucial to study the effect of ionizing radiations on nervous system due to the deleterious effects of low/ high radiations encountered by brain tumor patients or by astronauts in space. One of the main goals of NASA’s biological research is to advance the understanding of the response mechanisms to radiation-caused DNA damage. Earlier radiation studies on the CNS predominantly focused on neurons, with scant studies directly addressing the role of glial cells. Hence, we will focus our research on determining the major DNA repair pathways induced in these cells. We will study the effects of low/ high LET radiation on Ape1 in a OPC-like cell, the central glia-4 (CG-4), a rat bi-potential glial progenitor cell that can differentiate into OL or astrocytes. This project is funded by NASA for three years.

 

Selected Publications

  • Naidu M.D., Agarwal R., Pena L.A., Cunha L., Mezei M., Shen M., Wilson D.M. 3rd, Liu Y., Sanchez Z., Chaudhary P., Wilson S.H., and Waring M.J.
    Lucanthone and Its Derivative Hycanthone Inhibit Apurinic Endonuclease-1 (APE1) by Direct Protein Binding.
    PLoS One., 6(9):e23679. Epub 2011 Sep 15 (2011).  PubMed   pdf online
  • Naidu M.D., Mason J. M., Fung H., and Pena L.
    Radiation resistance in human glioma cell lines is determined by the DNA damage repair activity of apurinic endonuclease 1 (Ape1).
    (accepted in J.R.R. in Dec 2009).
  • Wang, H., Liu, S., Zhang, P., Zhang, S., Naidu M.D., Wang, H., and Wang, Y.
    S-phase cells are more radiosensitive to high linear energy transfer radiation.
    Intl. J. Rad. Oncol. Bio. Phys., 74(4):1236-1241 (2009).
  • Agarwal R. and Naidu M.D.
    Crystal structure of hApe1 in a new crystal form with a bound ligand: Implications on catalytic mechanism and its inhibition
    (PDB ID 2ISI, Deposition: 10/17/2006, Release: 10/31/2006)
  • Mason J., Naidu M.D., Barcia M., Porti D., Chavan S.S. and Chu C.C.
    IL-4-induced gene-1 is a leukocyte L-amino acid oxidase with an unusual acidic pH preference and lysosomal localization.
    J. Immunology, 173(7):4561-4567 (2004). PubMed
  • Naidu M.D. and Chander R.
    Immunomodulation of macrophages by radiodetoxified LPS of Salmonella typhimurium.
    Indian J. Exp. Biol., 37(3):283-289 (1999). PubMed
  • Naidu M.D., Chander R. and Nair P.M.
    Effect of gamma irradiation on chemical and biological properties of lipopolysaccharide from Salmonella typhimurium.
    Indian J. Exp. Biol., 36(6):588-592 (1998). PubMed
  • Kumthekar* M.M. and Katyare S.S.
    Altered kinetic attributes of Na++K+-ATPase activity in kidney, brain and erythrocyte membranes in alloxan-diabetic rats.
    Indian J. Exp. Biol., 30:26-32 (1992) (* Maiden Name).

 

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Last Modified: July 11, 2012
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