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Narayan G Avadhani, Ph.D.

Narayan G Avadhani, Ph.D.

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Graduate Group Affiliations

Contact information
Department of Biomedical Sciences
3800 Spruce Street
Room 189E Vet
Philadelphia, PA 19104
Office: 215-898-8819
Fax: 215-573-6651
Education:
B.Sc. (Chemistry/Physics)
Karnatak Science College, 1962.
Ph.D. (Biochemistry/Genetics)
University of Bombay, 1969.
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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

Chattopadhyay Mrittika, Chowdhury Anindya Roy, Feng Ting, Assenmacher Charles-Antoine, Radaelli Enrico, Guengerich F Peter, Avadhani Narayan G: Mitochondrially targeted cytochrome P450 2D6 is involved in monomethylamine-induced neuronal damage in mouse models. The Journal of biological chemistry 294(26): 10336-10348, Jun 2019.

Kijima Takashi, Nakagawa Hiroshi, Shimonosono Masataka, Chandramouleeswaran Prasanna M, Hara Takeo, Sahu Varun, Kasagi Yuta, Kikuchi Osamu, Tanaka Koji, Giroux Veronique, Muir Amanda B, Whelan Kelly A, Ohashi Shinya, Naganuma Seiji, Klein-Szanto Andres J, Shinden Yoshiaki, Sasaki Ken, Omoto Itaru, Kita Yoshiaki, Muto Manabu, Bass Adam J, Diehl J Alan, Ginsberg Gregory G, Doki Yuichiro, Mori Masaki, Uchikado Yasuto, Arigami Takaaki, Avadhani Narayan G, Basu Devraj, Rustgi Anil K, Natsugoe Shoji: Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells. Cellular and molecular gastroenterology and hepatology 7(1): 73-91, 2019.

Angireddy Rajesh, Kazmi Hasan Raza, Srinivasan Satish, Sun Li, Iqbal Jameel, Fuchs Serge Y, Guha Manti, Kijima Takashi, Yuen Tony, Zaidi Mone, Avadhani Narayan G: Cytochrome c oxidase dysfunction enhances phagocytic function and osteoclast formation in macrophages. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33(8): 9167-9181, Aug 2019.

Guha Manti, Srinivasan Satish, Guja Kip, Mejia Edison, Garcia-Diaz Miguel, Johnson F Brad, Ruthel Gordon, Kaufman Brett A, Rappaport Eric F, Glineburg M Rebecca, Fang Ji-Kang, Klein-Szanto Andres J, Nakagawa Hiroshi, Basha Jeelan, Kundu Tapas, Avadhani Narayan G: Correction to: HnRNPA2 is a novel histone acetyltransferase that mediates mitochondrial stress-induced nuclear gene expression. Cell discovery 5: 28, 2019.

Jackson Martina, Serada Nicole, Sheehan Maura, Srinivasan Satish, Mason Nicola, Guha Manti, Avadhani Narayan: Mitochondrial genome and functional defects in osteosarcoma are associated with their aggressive phenotype. PloS one 13(12): e0209489, 2018.

Guha Manti, Srinivasan Satish, Raman Pichai, Jiang Yuefu, Kaufman Brett A, Taylor Deanne, Dong Dawei, Chakrabarti Rumela, Picard Martin, Carstens Russ P, Kijima Yuko, Feldman Mike, Avadhani Narayan G: Aggressive triple negative breast cancers have unique molecular signature on the basis of mitochondrial genetic and functional defects. Biochimica et biophysica acta. Molecular basis of disease 1864(4 Pt A): 1060-1071, Apr 2018.

Ghosh Jyotirmoy, Chowdhury Anindya Roy, Srinivasan Satish, Chattopadhyay Mrittika, Bose Moumita, Bhattacharya Sabyasachi, Raza Haider, Fuchs Serge Y, Rustgi Anil K, Gonzalez Frank J, Avadhani Narayan G: Cigarette Smoke Toxins-Induced Mitochondrial Dysfunction and Pancreatitis Involves Aryl Hydrocarbon Receptor Mediated Cyp1 Gene Expression: Protective Effects of Resveratrol. Toxicological sciences : an official journal of the Society of Toxicology 166(2): 428-440, Dec 2018.

Peter Guengerich F, Avadhani Narayan G: Roles of Cytochrome P450 in Metabolism of Ethanol and Carcinogens. Advances in experimental medicine and biology 1032: 15-35, 2018.

Guha Manti, Srinivasan Satish, Johnson F Bradley, Ruthel Gordon, Guja Kip, Garcia-Diaz Miguel, Kaufman Brett A, Glineburg M Rebecca, Fang JiKang, Nakagawa Hiroshi, Basha Jeelan, Kundu Tapas, Avadhani Narayan G: hnRNPA2 mediated acetylation reduces telomere length in response to mitochondrial dysfunction. PloS one 13(11): e0206897, 2018.

Anandasadagopan Suresh Kumar, Singh Naveen M, Raza Haider, Bansal Seema, Selvaraj Venkatesh, Singh Shilpee, Chowdhury Anindya Roy, Leu Nicolae Adrian, Avadhani Narayan G: -Naphthoflavone-Induced Mitochondrial Respiratory Damage in Cyp1 Knockout Mouse and in Cell Culture Systems: Attenuation by Resveratrol Treatment. Oxidative medicine and cellular longevity 2017: 5213186, 2017.

Srinivasan Satish, Guha Manti, Kashina Anna, Avadhani Narayan G: Mitochondrial dysfunction and mitochondrial dynamics-The cancer connection. Biochimica et biophysica acta. Bioenergetics 1858(8): 602-614, Aug 2017.

Sepuri Naresh B V, Angireddy Rajesh, Srinivasan Satish, Guha Manti, Spear Joseph, Lu Bin, Anandatheerthavarada Hindupur K, Suzuki Carolyn K, Avadhani Narayan G: Mitochondrial LON protease-dependent degradation of cytochrome c oxidase subunits under hypoxia and myocardial ischemia. Biochimica et biophysica acta. Bioenergetics 1858(7): 519-528, Jul 2017.

Liu Peng, Ji Yaoting, Yuen Tony, Rendina-Ruedy Elizabeth, DeMambro Victoria E, Dhawan Samarth, Abu-Amer Wahid, Izadmehr Sudeh, Zhou Bin, Shin Andrew C, Latif Rauf, Thangeswaran Priyanthan, Gupta Animesh, Li Jianhua, Shnayder Valeria, Robinson Samuel T, Yu Yue Eric, Zhang Xingjian, Yang Feiran, Lu Ping, Zhou Yu, Zhu Ling-Ling, Oberlin Douglas J, Davies Terry F, Reagan Michaela R, Brown Aaron, Kumar T Rajendra, Epstein Solomon, Iqbal Jameel, Avadhani Narayan G, New Maria I, Molina Henrik, van Klinken Jan B, Guo Edward X, Buettner Christoph, Haider Shozeb, Bian Zhuan, Sun Li, Rosen Clifford J, Zaidi Mone: Blocking FSH induces thermogenic adipose tissue and reduces body fat. Nature 546(7656): 107-112, 06 2017.

Guha Manti, Srinivasan Satish, Guja Kip, Mejia Edison, Garcia-Diaz Miguel, Johnson F Brad, Ruthel Gordon, Kaufman Brett A, Rappaport Eric F, Glineburg M Rebecca, Fang Ji-Kang, Klein-Szanto Andres J, Klein Szanto Andres, Nakagawa Hiroshi, Basha Jeelan, Kundu Tapas, Avadhani Narayan G: HnRNPA2 is a novel histone acetyltransferase that mediates mitochondrial stress-induced nuclear gene expression. Cell discovery 2: 16045, 2016.

Guha Manti, Srinivasan Satish, Koenigstein Alexander, Zaidi Mone, Avadhani Narayan G: Enhanced osteoclastogenesis by mitochondrial retrograde signaling through transcriptional activation of the cathepsin K gene. Annals of the New York Academy of Sciences 1364: 52-61, Jan 2016.

Tanaka Koji, Whelan Kelly A, Chandramouleeswaran Prasanna M, Kagawa Shingo, Rustgi Sabrina L, Noguchi Chiaki, Guha Manti, Srinivasan Satish, Amanuma Yusuke, Ohashi Shinya, Muto Manabu, Klein-Szanto Andres J, Noguchi Eishi, Avadhani Narayan G, Nakagawa Hiroshi: ALDH2 modulates autophagy flux to regulate acetaldehyde-mediated toxicity thresholds. American journal of cancer research 6(4): 781-96, 2016.

Srinivasan Satish, Guha Manti, Avadhani Narayan G: Mitochondrial respiratory defects promote the Warburg effect and cancer progression. Molecular & cellular oncology 3(2): e1085120, Mar 2016.

Dong Dawei W, Srinivasan Satish, Guha Manti, Avadhani Narayan G: Defects in cytochrome c oxidase expression induce a metabolic shift to glycolysis and carcinogenesis. Genomics data 6: 99-107, Dec 2015.

Bajpai Prachi, Srinivasan Satish, Ghosh Jyotirmoy, Nagy Leslie D, Wei Shouzou, Guengerich F Peter, Avadhani Narayan G: Targeting of splice variants of human cytochrome P450 2C8 (CYP2C8) to mitochondria and their role in arachidonic acid metabolism and respiratory dysfunction. The Journal of biological chemistry 289(43): 29614-30, Oct 2014.

Bhattacharya Sabyasachi, Katlinski Kanstantsin V, Reichert Maximilian, Takano Shigetsugu, Brice Angela, Zhao Bin, Yu Qiujing, Zheng Hui, Carbone Christopher J, Katlinskaya Yuliya V, Leu N Adrian, McCorkell Kelly A, Srinivasan Satish, Girondo Melanie, Rui Hallgeir, May Michael J, Avadhani Narayan G, Rustgi Anil K, Fuchs Serge Y: Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury. EMBO molecular medicine 6(3): 384-97, 03 2014.

Bansal Seema, Biswas Gopa, Avadhani Narayan G: Mitochondria-targeted heme oxygenase-1 induces oxidative stress and mitochondrial dysfunction in macrophages, kidney fibroblasts and in chronic alcohol hepatotoxicity. Redox biology 2: 273-83, 2014.

Bansal Seema, Leu Adrian N, Gonzalez Frank J, Guengerich F Peter, Chowdhury Anindya Roy, Anandatheerthavarada Hindupur K, Avadhani Narayan G: Mitochondrial targeting of cytochrome P450 (CYP) 1B1 and its role in polycyclic aromatic hydrocarbon-induced mitochondrial dysfunction. The Journal of biological chemistry 289(14): 9936-51, Apr 2014.

Iqbal Jameel, Sun Li, Cao Jay, Yuen Tony, Lu Ping, Bab Itai, Leu N Adrian, Srinivasan Satish, Wagage Sagie, Hunter Christopher A, Nebert Daniel W, Zaidi Mone, Avadhani Narayan G: Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of Cyp1 enzymes. Proceedings of the National Academy of Sciences of the United States of America 110(27): 11115-20, Jul 2013.

Guha Manti, Avadhani Narayan G: Mitochondrial retrograde signaling at the crossroads of tumor bioenergetics, genetics and epigenetics. Mitochondrion 13(6): 577-91, Nov 2013.

Srinivasan Satish, Spear Joseph, Chandran Karunakaran, Joseph Joy, Kalyanaraman Balaraman, Avadhani Narayan G: Oxidative stress induced mitochondrial protein kinase A mediates cytochrome c oxidase dysfunction. PloS one 8(10): e77129, 2013.

Bansal Seema, Anandatheerthavarada Hindupur K, Prabu Govindaswamy K, Milne Ginger L, Martin Martha V, Guengerich F Peter, Avadhani Narayan G: Human cytochrome P450 2E1 mutations that alter mitochondrial targeting efficiency and susceptibility to ethanol-induced toxicity in cellular models. The Journal of biological chemistry 288(18): 12627-44, May 2013.

Bajpai Prachi, Sangar Michelle C, Singh Shilpee, Tang Weigang, Bansal Seema, Chowdhury Goutam, Cheng Qian, Fang Ji-Kang, Martin Martha V, Guengerich F Peter, Avadhani Narayan G: Metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by mitochondrion-targeted cytochrome P450 2D6: implications in Parkinson disease. The Journal of biological chemistry 288(6): 4436-51, Feb 2013.

Sleeper Meg M, Rosato Bradley P, Bansal Seema, Avadhani Narayan G: Mitochondrial dysfunction in myocardium obtained from clinically normal dogs, clinically normal anesthetized dogs, and dogs with dilated cardiomyopathy. American journal of veterinary research 73(11): 1759-64, Nov 2012.

Srinivasan Satish, Avadhani Narayan G: Cytochrome c oxidase dysfunction in oxidative stress. Free radical biology & medicine 53(6): 1252-63, Sep 2012.

Tang Weigang, Chowdhury Anindya Roy, Guha Manti, Huang Li, Van Winkle Thomas, Rustgi Anil K, Avadhani Narayan G: Silencing of IkBβ mRNA causes disruption of mitochondrial retrograde signaling and suppression of tumor growth in vivo. Carcinogenesis 33(9): 1762-8, Sep 2012.

Bansal Seema, Srinivasan Satish, Anandasadagopan Sureshkumar, Chowdhury Anindya Roy, Selvaraj Venkatesh, Kalyanaraman Balaraman, Joseph Joy, Avadhani Narayan G: Additive effects of mitochondrion-targeted cytochrome CYP2E1 and alcohol toxicity on cytochrome c oxidase function and stability of respirosome complexes. The Journal of biological chemistry 287(19): 15284-97, May 2012.

Ren Ling, Hong Sung-Hyeok, Chen Qing-Rong, Briggs Joseph, Cassavaugh Jessica, Srinivasan Satish, Lizardo Michael M, Mendoza Arnulfo, Xia Ashley Y, Avadhani Narayan, Khan Javed, Khanna Chand: Dysregulation of ezrin phosphorylation prevents metastasis and alters cellular metabolism in osteosarcoma. Cancer research 72(4): 1001-12, Feb 2012.

Avadhani Narayan G: Targeting of the same proteins to multiple subcellular destinations: mechanisms and physiological implications. The FEBS journal 278(22): 4217, Nov 2011.

Avadhani Narayan G, Sangar Michelle C, Bansal Seema, Bajpai Prachi: Bimodal targeting of cytochrome P450s to endoplasmic reticulum and mitochondria: the concept of chimeric signals. The FEBS journal 278(22): 4218-29, Nov 2011.

Yan Carol, Avadhani Narayan G, Iqbal Jameel: The effects of smoke carcinogens on bone. Current osteoporosis reports 9(4): 202-9, Dec 2011.

Raza Haider, Prabu Subbuswamy K, John Annie, Avadhani Narayan G: Impaired mitochondrial respiratory functions and oxidative stress in streptozotocin-induced diabetic rats. International journal of molecular sciences 12(5): 3133-47, 2011.

Iqbal Jameel, Zaidi Mone, Avadhani Narayan G: Cell signaling. Annals of the New York Academy of Sciences 1211: 3-8, Nov 2010.

Guha Manti, Fang Ji-Kang, Monks Robert, Birnbaum Morris J, Avadhani Narayan G: Activation of Akt is essential for the propagation of mitochondrial respiratory stress signaling and activation of the transcriptional coactivator heterogeneous ribonucleoprotein A2. Molecular biology of the cell 21(20): 3578-89, Oct 2010.

Sondheimer Neal, Fang Ji-Kang, Polyak Erzsebet, Falk Marni J, Avadhani Narayan G: Leucine-rich pentatricopeptide-repeat containing protein regulates mitochondrial transcription. Biochemistry 49(35): 7467-73, Sep 2010.

Sangar Michelle C, Bansal Seema, Avadhani Narayan G: Bimodal targeting of microsomal cytochrome P450s to mitochondria: implications in drug metabolism and toxicity. Expert opinion on drug metabolism & toxicology 6(10): 1231-51, Oct 2010.

Bansal Seema, Liu Chuan-Peng, Sepuri Naresh B V, Anandatheerthavarada Hindupur K, Selvaraj Venkatesh, Hoek Jan, Milne Ginger L, Guengerich F Peter, Avadhani Narayan G: Mitochondria-targeted cytochrome P450 2E1 induces oxidative damage and augments alcohol-mediated oxidative stress. The Journal of biological chemistry 285(32): 24609-19, Aug 2010.

Srinivasan Satish, Koenigstein Alexander, Joseph Joy, Sun Li, Kalyanaraman B, Zaidi Mone, Avadhani Narayan G: Role of mitochondrial reactive oxygen species in osteoclast differentiation. Annals of the New York Academy of Sciences 1192: 245-52, Mar 2010.

Guha Manti, Tang Weigang, Sondheimer Neal, Avadhani Narayan G: Role of calcineurin, hnRNPA2 and Akt in mitochondrial respiratory stress-mediated transcription activation of nuclear gene targets. Biochimica et biophysica acta 1797(6-7): 1055-65, Jun-Jul 2010.

Sangar Michelle Cook, Anandatheerthavarada Hindupur K, Martin Martha V, Guengerich F Peter, Avadhani Narayan G: Identification of genetic variants of human cytochrome P450 2D6 with impaired mitochondrial targeting. Molecular genetics and metabolism 99(1): 90-7, Jan 2010.

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Last updated: 06/10/2020
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