1986: M.S. Biochemistry. S.K. University, Anantapur, India
1992: Ph.D. Neurochemistry. Natl.Inst. Mental Health & Neurosciences, Bangalore, India

Member of Society for Neuroscience
Member of International Society for Neurochemistry
Member of International Society for Xenobiotic studies
Member of Drug information Association (DIA)

Project I: APP mediated mitochondrial injury in aging neurons: The main focus of this project is to understand the Alzheimer’s disease relevance of mitochondrial targeting of amyloid precursor protein (APP). The principle objectives of this project are (a) to precisely characterize the molecular events involved in the targeting of APP to mitochondria and associated mitochondrial dysfunctions, (b) to understand the role of APP mediated mitochondrial dysfunction in accumulation of Beta 42 in the secretory pathway and (c) the role of mitochondrial associated APP in neuronal degeneration using cortical neuronal cell culture, post mortem human brains affected with AD and rodent models of AD. This project is funded by NIH/NIA.

Project II: Consequences of cytochrome P450 (P450) mediated neurotransmitters metabolism in neurological disorders: This project aims to understand the cross talk between brain P450 mediated catecholamine metabolism and Parkinson’s disease (PD) associated proteins such as alpha synuclein, DJ1 and parkin in the pathogenesis of PD. The major objectives of this project are (a) to characterize the involvement of P450 in the reactive metabolism of dopa and dopamine, (b) to investigate the effect of P450 mediated reactive metabolism of dopamine on mitochondrial dysfunction, aggregation of alpha synuclein and selective loss of dopaminergic neurons using neuronal cell culture, post mortem human brains affected with PD and rodent models of PD.

(1999-present)

(1) Anandatheerthavarada, H. K. , Vijayasarathy, C., Bhagwat, S. V., Biswas, G., Mullick, J. and Avadhani, N. G. (1999). Physiological role of the N-terminal processed P4501A1 targeted to mitochondria in erythromycin metabolism and reversal of erythromycin mediated inhibition of mitochondrial protein synthesis. J. Biol. Chem. 274: 6617-6625.

(2) Anandatheerthavarada, H. K. , Biswas, G., Mullick, J., Sepuri, N.B., Laszlo, O., Pain, D. and Avadhani, N. G. (1999) Dual targeting of cytochrome P4502B1 to endoplasmic reticulum and mitochondria involves a novel signal activation by cyclic AMP-dependent phosphorylation at Ser128. EMBO J.18: 5494-5504.

(3) Adebanjo, O. A., Anandatheerthavarada, H.K. , Koval AP, Moonga, BS., Biswas, G., Sun, Li., Sodam BR, Bevis PJ, Huang, C. L, Epstein S. H., Avadhani, N. G. and Zaidi, M.( 1999) A new function for CD38/ADP-ribosyl cyclase in nuclear Ca²⁺ homeostasis. Nature Cell Biol.1: 409-414.

(4) Biswas, G., Adebanjo,* O. A., Freedman*, B.D., Anandatheerthavarada,* H.K , Vijayasarathy, C., Zaidi, M., Kotlikoff, M. and Avadhani, N. G. (1999) Retrograde Ca2+ signaling in C2C12 skeletal Myocytes in response to mitochondrial genetic and metabolic stress: A Novel mode of Inter-Organelle cross talk (*equal contribution) EMBO J. 18:522-533.

(5) Bhagwat, S. V., Biswas, G., Anandatheerthavarada, H. K. , Addya, S., Pandak, W. and Avadhani, N. G. (1999) Dual targeting property of the N- terminal signal of P4501A1: targeting of heterologous proteins to both the endoplasmic reticulum and mitochondria. J. Biol. Chem. 274:24014-22

(6) Adebanjo, O. A., Biswas, G., Moonga, B. S., Anandatheerthavarada, H. K. , Sun, L., Bevis, P. J. R., Sodam, B. R., Lai, F. A., Avadhani, N.G. and Zaidi, M. (2000) Novel biochemical and functional insights into nuclear Ca2+ transport through IP3Rs and RyRs in osteoblasts. Am. J. Physiol. 278: 84-51

(7) Boopathi, E., Anandatheerthavarada, H. K. , Bhagwat, S.V., Biswas, G., Fang, J. K. and Avadhani, N.G. (2000) Accumulation of mitochondrial P450MT2, NH2-terminal truncated cytochrome P4501A1 in rat brain during chronic treatment with beta-naphthoflavone. A ROLE IN THE METABOLISM OF NEUROACTIVE DRUGS. J. Biol. Chem. 275:34415-23

(8) Anandatheerthavarada, H.K. , Amuthan, G., Biswas, G., Robin, M-A., Murali, R., Waterman, M.R. and Avadhani, N.G. (2001) Evolutionarily divergent electron donor proteins interact with P450MT2 through the same helical domain but different contact points. EMBO. J .20:2394-2403

(9) Mullick, J., Anandatheerthavarada, H.K. , Amuthan, G., Bhagwat , S.V., Biswas, G., C. Vijayasarathy., Bhat , N.K., Reddy, S.E.P., Rao, V. and Avadhani, N.G. (2001) Physical Interaction and Functional Synergy Between Glucocorticoid Receptor and Ets2 Proteins for Transcription Activation of the Rat Cytochrome P450c27 Promoter. J. Biol. Chem. 276:18007-18017

(10) Robin, M-A., Anandatheerthavarada, H.K. , Fang, J-K., Cudic, M., Otvos, L., and Avadhani, N.G. (2001) Mitochondrial targeted cytochrome P450 (P450MT5) contains an intact N-terminus and requires mitochondrial specific electron transfer proteins for activity. J.Biol.Chem. 276:24680-24689

(11) Adebanjo, O.A*., Koval, A*., Anandatheerthavarada H.K*. , Moonga, B.S., Xue, B Wu, Biswas, G., Iqbal, J., Bevis, P.J.R., Kumegawa, M., Abe, E., Avadhani, N.G., Li, S and Zaidi, M. (2002) A novel mechanism for coupling cellular intermediary metabolism to cytosolic Ca2+ signaling via CD38/ADP- Ribosyl cyclase, putative intracellular NAD+ sensor. FASEB.J. 16:302-314 (*joint first authors)

(12) Robin, M-A., Anandatheerthavarada, H.K. , Biswas, G., Naresh Babu V. Sepuri., Gordon, D.M., Pain, D and Avadhani, N.G. (2002) Bimodal targeting of microsomal CYP2E1 to mitochondria through activation of an N-terminal chimeric signal by cAMP mediated phosphorylation. J.Biol.Chem. 277:40583-40593

(13) Amuthan, G., Biswas, G., Anandatheerthavarada, H,K. , Vijayasarathy, C., Shepard, H and Avadhani, N.G. (2002) Mitochondrial stress-induced phenotypic changes and invasive behaviour in human lung carcinoma A549 cells. Oncogene.21:7839-7849.

(14) Anandatheerthavarada, H.K. , Biswas, G., Robin, M-A and Avadhani, N.G. (2003) Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells.
J.Cell. Biol. 161:41-54.

(15) Biswas, G*., Anandatheerthavarada, H.K*. , Zaidi, M and Avadhani, N.G. (2003) Mitochondria to nucleus stress signaling: a distinctive mechanism of NFkappaB/Rel activation through calcineurin-mediated inactivation of IkappaBbeta . J.Cell.Biol. 161:507-519. (* joint first authors)

(16) Robin, M.A., Prabu, S.K., Raza, H., Anandatheerthavarada, H.K. , and Avadhani NG. (2003). Phosphorylation enhances mitochondrial targeting of GSTA4-4 through increased affinity for binding to cytoplasmic Hsp70. J.Biol.Chem.278:18960-18970.

(17) Biswas,G., Anandatheerthavarada, H.K. , and Avadhani, N.G. Mechanism of Mitochondrial Stress-Induced Resistance to Apoptosis in Mitochondrial DNA Depleted C2C12 Myocytes. Cell Death and Differentiation (in press)

Grants:

Current lab Members: