Molecular Neurotoxicology Laboratory

Director- Govindarajan Ramesh, Ph.D

Dr. Govindarajan Ramesh is an Assistant Professor in the Department of Biology. Dr. Ramesh’s primary area of research interest is to study the biochemical and molecular mechanisms involved in metal toxicity particularly arsenic, lead and manganese. The main focus is to study low-level exposure to metal mixtures that alters brain-signaling mechanisms. The second area is to examine if the concentration of metal mixtures which alter signaling mechanism does also alter the molecular events particularly the immediate early response genes (IERGs),i.e., NF-kB transcription factor and signal responsive kinases in the brain. His laboratory is also focusing on research on microgravity by delineating the effects involvement of oxidative stress on signaling mechanisms in the mouse brain. Microgravitational environment in space alters many physiological functions in astronauts which induce inflammatory response and thus affect immune functions. To optimally develop techniques that prevent or alleviate the deleterious effects of space flight, altered cellular and molecular mechanisms due to microgravity are being explored. The main thrust of his research is to elucidate the molecular mechanisms underlying the effects of stress on calcium homeostasis, which in turn may alter the stress activated transcription factor NF-kB, and kinases, such as MAPKK and JNK in the mouse brain. Abnormal activation of NF-kB has been found to induce pathological symptoms such as inflammation. The involvement of NF-kB makes it an important target for therapeutic manipulation and the development of a countermeasure that will improve and maintain the health of crewmembers during short and long space flights. Part of the overall goal is also to train undergraduate, graduate and post-doctoral students in molecular neurotoxicology and space research.  He has published numerous research papers in peer reviewed journals. His laboratory is well equipped to carry out state-of-the art molecular biology and neurotoxicology research. Major funding of his research project comes from Research Center for Minority Institution [(RCMI)/National Institutes of Health (NIH)], National Science Foundation and National Aeronautics and Space Administration [(NASA)].

Laboratory Personnel:

Dr. Felix Kumar- Visiting Assistant Professor

Kimberly Wise- Graduate Student (Env. Toxicology)                    

Johnny Barr- Graduate Student (Env. Toxicology)

Brian Jones- Graduate Student (Biology)                        

Tony Henry- Graduate Student (Biology)                   

Nike Blackshire- Undergraduate Student (Chemistry)              

Rajeshwari Yog- Undergraduate Student (Biology)                      

Selected Publications:

Jadhav, A. L. and Ramesh, G. T.  (1997). " Pb-induced Alterations in Tyrosine Hydroxylase  Acitivity  in Rat Brain". Mol .Cell. Biochem, 175, 137-141.

Ramesh, G. T. and Jadhav, A. L.  (1998). "Region Specific Alterations in Tyrosine Hydroxylase Activitiy in Rats Exposed to Lead". Mol. Cell. Biochem  189, 19-24.

Ramesh, G. T. Sunil, K. M. Aggarwal, B. B and Jadhav, A. L.  (1999) ALead activates Nuclear Transcription Factor kappa B, Activator Protein-1 and N-terminal c-Jun Kinase in Pheochromacytoma cells. Toxicol. Appl. Pharmacol. 155(3), 280-286.

Ramesh, G. T. Jadhav, A. L and Palur, G. (2000) “Contribution of PKC and Glutamate in Pb-induced  cytotoxicity” Tox. Lett. 115, 89-98.

Gedeon, Y. Ramesh, G. T. Jadhav, A. L (2001) Changes in mesocorticolimbic dopamine and D(1)/D(2) receptor levels after low level lead exposure: a time  course study. Tox. Lett.  123, 217-226.

Ramesh, G. T. and Jadhav, A. L.  (2001). "Levels of Protein kinase C and Nitric oxide synthase activity in rats exposed to sub chronic low level lead. Mol. Cell. Biochem .  121, 27-33.

Ramesh, G. T. Sunil, K. M. Aggarwal, B. B and Jadhav, A. L. (2001) “Lead exposure activates Nuclear Transcription Factor kappa B, Activator Protein-1 and c-Jun N-terminal Kinase and caspase in the rat brain. Tox. Lett.  123, 195-207.

Kulkarni, A. D. Yamauchi, K. Hales, N.H.  Ramesh, V. Ramesh, G. T. Sundareasan, A. Andrassy, A. Pellis, N. R.   (2002) "Nutrition beyond nutrition: Plausibility of immunotrophic nutrition for space travel" Clinical Nutrition, 21, 231-   238.

Ramesh, G. T. Ghosh D and Gunasekar, P. G. (2002) “Activation of Early Signaling Transcription Factor NF-kB following manganese exposure linked to oxidative stress”.  Tox. Lett.  136(2), 155-162.

WisW Wise, K.  Manna, S., Barr, J. Palur, G and Ramesh, G. T. (2004) " Activation of Activator Protein-1 DNA Binding Activity Due to Low Levels of Manganese Exposure  in Pheochromocytoma Tox. Lett. 147(3), 237-244.

Cells”.

Sarkar A., Sreenivasan Y., Ramesh G. T and Manna S. K. (2004) “Beta-D-glucoside suppresses TNF-induced activation of nuclear transcription factor kappaB but potentiates apoptosis”. J Biol Chem. 279(32), 33768-33781.

Felix, K., Wise, K., Manna, S., Wilson, B. L., Thomas, R. Barr, J., Kulkarni, A. Pellis. N. R. and Ramesh G. T. (2004) Altered Cytokine Expression in Tissues of Mice Subjected to Simulated Microgravity”. Mol. Cell. Biochem .(In press)

Ongoing Research Support

 1.        Title: Microgravity and Oxidative Stress

Agency: Texas Southern University-Seed Grant-2002-2004

Amount: $18,000

Status: Funded

2.         Title: Nano Bio-Technologies for Aerospace Systems

            Agency: NASA-URETI-2002-2007.

            Amount: $225,000

Status: Funded

3.         Title: Studies with in vivo Model of Simulated Microgravity on Calcium Homeostasis and   Expression of Immediate Early Response Genes in Mouse Brain

Agency: NASA - 2002-2005.

Amount: $205,000

Status: Funded

4.         Title: NASA Research Center for Biotechnology and Environmental Health

            Agency: NASA-URC-2003-2008.

            Amount: $750,000

Status: Funded

5.         Title: Evaluation of Biochemical Effects of Endocrine Disruptors on Dopamine Metabolism in Neuronal cells.

Agency: National Science Foundation 2004-2007.

Amount: $300,000

Status: Funded