Penn Veterinary Medicine | University of Pennsylvania

Description of Research Expertise

The research in Dr. Avadhani's laboratory is focused on the following aspects of mitochondrial genetics and regulation of mitochondrial membrane biogenesis in mammalian cells:

1. Mechanisms of dual targeting of cytochrome P450 and related proteins to ER and mitochondria and mechanisms of activation of the chimeric N-terminal signal by cAMP and other physiological factors.

2. Characterization of a novel mitochondria-to-nucleus stress signaling in cells subjected to mitochondrial specific genetic, and or, metabolic stress, which operates through altered [Ca2+]c, and the role of mitochondrial stress signaling in tumor progression and metastasis.

3. Regulation of cytochrome oxidase gene expression, and modulation of enzyme assembly/activity under chemical and oxidative stress conditions.

4. Role of mitochondrial stress signaling in Embryonic Stem Cell function/differentiation, and mammalian mitochondrial transcription under chemical and oxidative stress in ES cells.

Selected Publications

Biswas, Gopa. Srinivasan, Satish. Anandatheerthavarada, Hindupur K. Avadhani, Narayan G.: Dioxin-mediated tumor progression through activation of mitochondria-to-nucleus stress signaling. Proceedings of the National Academy of Sciences of the United States of America 105(1): 186-91, Jan 8 2008.

Srinivasan, Satish. Avadhani, Narayan G.: Hypoxia-mediated mitochondrial stress in RAW264.7 cells induces osteoclast-like TRAP-positive cells. Annals of the New York Academy of Sciences 1117: 51-61, Nov 2007.

Sepuri, Naresh B V. Yadav, Sanjay. Anandatheerthavarada, Hindupur K. Avadhani, Narayan G.: Mitochondrial targeting of intact CYP2B1 and CYP2E1 and N-terminal truncated CYP1A1 proteins in Saccharomyces cerevisiae--role of protein kinase A in the mitochondrial targeting of CYP2E1. FEBS Journal 274(17): 4615-30, Sep 2007.

Hardy, Micael. Rockenbauer, Antal. Vasquez-Vivar, Jeannette. Felix, Christopher. Lopez, Marcos. Srinivasan, Satish. Avadhani, Narayan. Tordo, Paul. Kalyanaraman, B.: Detection, characterization, and decay kinetics of ROS and thiyl adducts of mito-DEPMPO spin trap. Chemical Research in Toxicology 20(7): 1053-60, Jul 2007.

Guha, Manti. Srinivasan, Satish. Biswas, Gopa. Avadhani, Narayan G.: Activation of a novel calcineurin-mediated insulin-like growth factor-1 receptor pathway, altered metabolism, and tumor cell invasion in cells subjected to mitochondrial respiratory stress. Journal of Biological Chemistry 282(19): 14536-46, May 11 2007.

Spear, Joseph F. Prabu, Subbuswamy K. Galati, Domenico. Raza, Haider. Anandatheerthavarada, Hindupur K. Avadhani, Narayan G.: beta1-Adrenoreceptor activation contributes to ischemia-reperfusion damage as well as playing a role in ischemic preconditioning. American Journal of Physiology - Heart & Circulatory Physiology 292(5): H2459-66, May 2007.

Fang, Ji-Kang. Prabu, Subbuswamy K. Sepuri, Naresh B. Raza, Haider. Anandatheerthavarada, Hindupur K. Galati, Domenico. Spear, Joseph. Avadhani, Narayan G.: Site specific phosphorylation of cytochrome c oxidase subunits I, IVi1 and Vb in rabbit hearts subjected to ischemia/reperfusion. FEBS Letters 581(7): 1302-10, Apr 3 2007.

Dasari, Venkata Ramesh. Anandatheerthavarada, Hindupur K. Robin, Marie-Anne. Boopathi, Ettickan. Biswas, Gopa. Fang, Ji-Kang. Nebert, Daniel W. Avadhani, Narayan G.: Role of protein kinase C-mediated protein phosphorylation in mitochondrial translocation of mouse CYP1A1, which contains a non-canonical targeting signal. Journal of Biological Chemistry 281(41): 30834-47, Oct 13 2006.

Wang, Ying. Biswas, Gopa. Prabu, Subbuswamy K. Avadhani, Narayan G.: Modulation of mitochondrial metabolic function by phorbol 12-myristate 13-acetate through increased mitochondrial translocation of protein kinase Calpha in C2C12 myocytes. Biochemical Pharmacology 72(7): 881-92, Sep 28 2006.

Devi, Latha. Prabhu, Badanavalu M. Galati, Domenico F. Avadhani, Narayan G. Anandatheerthavarada, Hindupur K.: Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction. Journal of Neuroscience 26(35): 9057-68, Aug 30 2006.

Prabu, Subbuswamy K. Anandatheerthavarada, Hindupur K. Raza, Haider. Srinivasan, Satish. Spear, Joseph F. Avadhani, Narayan G.: Protein kinase A-mediated phosphorylation modulates cytochrome c oxidase function and augments hypoxia and myocardial ischemia-related injury. Journal of Biological Chemistry 281(4): 2061-70, Jan 27 2006.

Biswas, Gopa. Guha, Manti. Avadhani, Narayan G.: Mitochondria-to-nucleus stress signaling in mammalian cells: nature of nuclear gene targets, transcription regulation, and induced resistance to apoptosis. Gene 354: 132-9, Jul 18 2005.

Biswas, G. Anandatheerthavarada, H K. Avadhani, N G.: Mechanism of mitochondrial stress-induced resistance to apoptosis in mitochondrial DNA-depleted C2C12 myocytes. Cell Death & Differentiation 12(3): 266-78, Mar 2005.

Nikonova, Elena V. Vijayasarathy, Camasamudram. Zhang, Lin. Cater, Jacqueline R. Galante, Raymond J. Ward, Stephen E. Avadhani, Narayan G. Pack, Allan I.: Differences in activity of cytochrome C oxidase in brain between sleep and wakefulness. Sleep 28(1): 21-7, Jan 1 2005.

Boopathi, Ettickan. Lenka, Nibedita. Prabu, Subbuswamy K. Fang, Ji-Kang. Wilkinson, Frank. Atchison, Michael. Giallongo, Agata. Avadhani, Narayan G.: Regulation of murine cytochrome c oxidase Vb gene expression during myogenesis: YY-1 and heterogeneous nuclear ribonucleoprotein D-like protein (JKTBP1) reciprocally regulate transcription activity by physical interaction with the BERF-1/ZBP-89 factor. Journal of Biological Chemistry 279(34): 35242-54, Aug 20 2004.

Butow, Ronald A. Avadhani, Narayan G.: Mitochondrial signaling: the retrograde response. [Review] [119 refs] Molecular Cell 14(1): 1-15, Apr 9 2004.

Levy, Richard J. Vijayasarathy, C. Raj, Nichelle R. Avadhani, Narayan G. Deutschman, Clifford S.: Competitive and noncompetitive inhibition of myocardial cytochrome C oxidase in sepsis. Shock 21(2): 110-4, Feb 2004.