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Dr. Shyam Biswal

(410) 955-8964 (p)

Associate Professor of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health
Joint Appointment in Oncology


PhD, Indian Institute of Technology

Research Summary

The Biswal lab studies the mechanisms of susceptibility to environmental lung diseases, such as cancer, COPD and asthma. We have identified that transcription factor, Nrf2, is a critical modifier of inflammation which determines susceptibility to these diseases. Translational research focusing on elucidation of pathways and mechanism by which Nrf2 regulates pathogenesis of inflammatory diseases is in progress. These studies are helping in devising novel strategies for intervening cancer and other diseases where inflammation play a key role.

Journal Citations

Osburn, W.O.; Wakabayashi, N.; Misra, V.; Nilles, T.; Biswal, S.; Trush, M.A.; Kensler, T.W. Nrf2 regulates an adaptive response protecting against oxidative damage following diquat-mediated formation of superoxide anion. Arch Biochem Biophys. 2006 Oct 1;454(1):7-15.

Singh, A.; Misra, V.; Thimmulappa, R.K.; Lee, H.; Ames, S.; Hoque, M.O.; Herman, J.G.; Baylin, S.B.; Sidransky, D.; Gabrielson, E.; Brock, M.V.; Biswal, S. Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. PLoS Med. 2006 Oct;3(10):e420.

Singh, A.; Rangasamy, T.; Thimmulappa, R.K.; Lee, H.; Osburn, W.O.; Brigelius-Flohe, R.; Kensler, T.W.; Yamamoto, M.; Biswal, S. Glutathione peroxidase 2, the major cigarette smoke-inducible isoform of GPX in lungs, is regulated by Nrf2. Am J Respir Cell Mol Biol. 2006 Dec;35(6):639-650.

Thimmulappa, R.K.; Scollick, C.; Traore, K.; Yates, M.; Trush, M.A.; Liby, K.T.; Sporn, M.B.; Yamamoto, M.; Kensler, T.W.; Biswal, S. Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem Biophys Res Commun. 2006 Dec 29;351(4):883-889.

Tuder, R.M.; Yoshida, T.; Fijalkowka, I.; Biswal, S.; Petrache, I. Role of lung maintenance program in the heterogeneity of lung destruction in emphysema. Proceedings of the American Thoracic Society. 2006 Nov;3(8):673-679.

Huang, K.; Mitzner, W.; Rabold, R.; Schofield, B.; Lee, H.; Biswal, S.; Tankersley, C.G. Variation in senescent-dependent lung changes in inbred mouse strains. J Appl Physiol. 2007 Apr;102(4):1632-1639.

Kensler, T.W.; Wakabayashi, N.; Biswal, S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annual review of pharmacology and toxicology. 2007;47:89-116.

Misra, V.; Lee, H.; Singh, A.; Huang, K.; Thimmulappa, R.K.; Mitzner, W.; Biswal, S.; Tankersley, C.G. Global expression profiles from C57BL/6J and DBA/2J mouse lungs to determine aging-related genes. Physiol Genomics. 2007 Nov 14;31(3):429-440.

Papaiahgari, S.; Yerrapureddy, A.; Reddy, S.R.; Reddy, N.M.; Dodd, O.J.; Crow, M.T.; Grigoryev, D.N.; Barnes, K.; Tuder, R.M.; Yamamoto, M.; Kensler, T.W.; Biswal, S.; Mitzner, W.; Hassoun, P.M.; Reddy, S.P. Genetic and pharmacologic evidence links oxidative stress to ventilator-induced lung injury in mice. Am J Respir Crit Care Med. 2007 Dec 15;176(12):1222-1235.

Reddy, N.M.; Kleeberger, S.R.; Cho, H.Y.; Yamamoto, M.; Kensler, T.W.; Biswal, S.; Reddy, S.P. Deficiency in Nrf2-GSH signaling impairs type II cell growth and enhances sensitivity to oxidants. Am J Respir Cell Mol Biol. 2007 Jul;37(1):3-8.

Reddy, N.M.; Kleeberger, S.R.; Yamamoto, M.; Kensler, T.W.; Scollick, C.; Biswal, S.; Reddy, S.P. Genetic dissection of the Nrf2-dependent redox signaling-regulated transcriptional programs of cell proliferation and cytoprotection. Physiol Genomics. 2007 Dec 19;32(1):74-81.

Rulli, S.J., Jr.; Hibbert, C.S.; Mirro, J.; Pederson, T.; Biswal, S.; Rein, A. Selective and nonselective packaging of cellular RNAs in retrovirus particles. J Virol. 2007 Jun;81(12):6623-6631.

Shah, Z.A.; Li, R.C.; Thimmulappa, R.K.; Kensler, T.W.; Yamamoto, M.; Biswal, S.; Dore, S. Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury. Neuroscience. 2007 Jun 15;147(1):53-59.

Shin, S.; Wakabayashi, N.; Misra, V.; Biswal, S.; Lee, G.H.; Agoston, E.S.; Yamamoto, M.; Kensler, T.W. NRF2 modulates aryl hydrocarbon receptor signaling: influence on adipogenesis. Mol Cell Biol. 2007 Oct;27(20):7188-7197.

Thimmulappa, R.K.; Fuchs, R.J.; Malhotra, D.; Scollick, C.; Traore, K.; Bream, J.H.; Trush, M.A.; Liby, K.T.; Sporn, M.B.; Kensler, T.W.; Biswal, S. Preclinical evaluation of targeting the Nrf2 pathway by triterpenoids (CDDO-Im and CDDO-Me) for protection from LPS-induced inflammatory response and reactive oxygen species in human peripheral blood mononuclear cells and neutrophils. Antioxid Redox Signal. 2007 Nov;9(11):1963-1970.

Wang, J.; Fields, J.; Zhao, C.; Langer, J.; Thimmulappa, R.K.; Kensler, T.W.; Yamamoto, M.; Biswal, S.; Dore, S. Role of Nrf2 in protection against intracerebral hemorrhage injury in mice. Free Radic Biol Med. 2007 Aug 1;43(3):408-414.

Fujihara, M.; Nagai, N.; Sussan, T.E.; Biswal, S.; Handa, J.T. Chronic cigarette smoke causes oxidative damage and apoptosis to retinal pigmented epithelial cells in mice. PLoS ONE. 2008;3(9):e3119.

Malhotra, D.; Thimmulappa, R.; Navas-Acien, A.; Sandford, A.; Elliott, M.; Singh, A.; Chen, L.; Zhuang, X.; Hogg, J.; Pare, P.; Tuder, R.M.; Biswal, S. Decline in NRF2-regulated antioxidants in chronic obstructive pulmonary disease lungs due to loss of its positive regulator, DJ-1. Am J Respir Crit Care Med. 2008 Sep 15;178(6):592-604.

McGrath-Morrow, S.; Rangasamy, T.; Cho, C.; Sussan, T.; Neptune, E.; Wise, R.; Tuder, R.M.; Biswal, S. Impaired lung homeostasis in neonatal mice exposed to cigarette smoke. Am J Respir Cell Mol Biol. 2008 Apr;38(4):393-400.

Moens, A.L.; Takimoto, E.; Tocchetti, C.G.; Chakir, K.; Bedja, D.; Cormaci, G.; Ketner, E.A.; Majmudar, M.; Gabrielson, K.; Halushka, M.K.; Mitchell, J.B.; Biswal, S.; Channon, K.M.; Wolin, M.S.; Alp, N.J.; Paolocci, N.; Champion, H.C.; Kass, D.A. Reversal of cardiac hypertrophy and fibrosis from pressure overload by tetrahydrobiopterin: efficacy of recoupling nitric oxide synthase as a therapeutic strategy. Circulation. 2008 May 20;117(20):2626-2636.

Singh, A.; Boldin-Adamsky, S.; Thimmulappa, R.K.; Rath, S.K.; Ashush, H.; Coulter, J.; Blackford, A.; Goodman, S.N.; Bunz, F.; Watson, W.H.; Gabrielson, E.; Feinstein, E.; Biswal, S. RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene expression in non-small cell lung cancer inhibits tumor growth and increases efficacy of chemotherapy. Cancer Res. 2008 Oct 1;68(19):7975-7984.

Sussan, T.E.; Jun, J.; Thimmulappa, R.; Bedja, D.; Antero, M.; Gabrielson, K.L.; Polotsky, V.Y.; Biswal, S. Disruption of Nrf2, a key inducer of antioxidant defenses, attenuates ApoE-mediated atherosclerosis in mice. PLoS ONE. 2008;3(11):e3791.

Thimmulappa, R.K.; Rangasamy, T.; Alam, J.; Biswal, S. Dibenzoylmethane activates Nrf2-dependent detoxification pathway and inhibits benzo(a)pyrene induced DNA adducts in lungs. Medicinal chemistry (Shariqah (United Arab Emirates)). 2008 Sep;4(5):473-481.

Williams, M.A.; Rangasamy, T.; Bauer, S.M.; Killedar, S.; Karp, M.; Kensler, T.W.; Yamamoto, M.; Breysse, P.; Biswal, S.; Georas, S.N. Disruption of the transcription factor Nrf2 promotes pro-oxidative dendritic cells that stimulate Th2-like immunoresponsiveness upon activation by ambient particulate matter. J Immunol. 2008 Oct 1;181(7):4545-4559.

An, S.S.; Kim, J.; Ahn, K.; Trepat, X.; Drake, K.J.; Kumar, S.; Ling, G.; Purington, C.; Rangasamy, T.; Kensler, T.W.; Mitzner, W.; Fredberg, J.J.; Biswal, S. Cell stiffness, contractile stress and the role of extracellular matrix. Biochem Biophys Res Commun. 2009 May 15;382(4):697-703.

Bivalacqua, T.J.; Sussan, T.E.; Gebska, M.A.; Strong, T.D.; Berkowitz, D.E.; Biswal, S.; Burnett, A.L.; Champion, H.C. Sildenafil inhibits superoxide formation and prevents endothelial dysfunction in a mouse model of secondhand smoke induced erectile dysfunction. J Urol. 2009 Feb;181(2):899-906.

Harvey, C.J.; Thimmulappa, R.K.; Singh, A.; Blake, D.J.; Ling, G.; Wakabayashi, N.; Fujii, J.; Myers, A.; Biswal, S. Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress. Free Radic Biol Med. 2009 Feb 15;46(4):443-453.

Le, A.; Zielinski, R.; He, C.; Crow, M.T.; Biswal, S.; Tuder, R.M.; Becker, P.M. Pulmonary epithelial neuropilin-1 deletion enhances development of cigarette smoke-induced emphysema. Am J Respir Crit Care Med. 2009 Sep 1;180(5):396-406.

Malhotra, D.; Thimmulappa, R.; Vij, N.; Navas-Acien, A.; Sussan, T.; Merali, S.; Zhang, L.; Kelsen, S.G.; Myers, A.; Wise, R.; Tuder, R.; Biswal, S. Heightened endoplasmic reticulum stress in the lungs of patients with chronic obstructive pulmonary disease: the role of Nrf2-regulated proteasomal activity. Am J Respir Crit Care Med. 2009 Dec 15;180(12):1196-1207.

McGrath-Morrow, S.; Lauer, T.; Yee, M.; Neptune, E.; Podowski, M.; Thimmulappa, R.K.; O'Reilly, M.; Biswal, S. Nrf2 increases survival and attenuates alveolar growth inhibition in neonatal mice exposed to hyperoxia. American journal of physiology. 2009 Apr;296(4):L565-573.

Nagai, N.; Thimmulappa, R.K.; Cano, M.; Fujihara, M.; Izumi-Nagai, K.; Kong, X.; Sporn, M.B.; Kensler, T.W.; Biswal, S.; Handa, J.T. Nrf2 is a critical modulator of the innate immune response in a model of uveitis. Free Radic Biol Med. 2009 Aug 1;47(3):300-306.

Rangasamy, T.; Misra, V.; Zhen, L.; Tankersley, C.G.; Tuder, R.M.; Biswal, S. Cigarette smoke-induced emphysema in A/J mice is associated with pulmonary oxidative stress, apoptosis of lung cells, and global alterations in gene expression. American journal of physiology. 2009 Jun;296(6):L888-900.

Rangasamy, T.; Williams, M.A.; Bauer, S.; Trush, M.A.; Emo, J.; Georas, S.N.; Biswal, S. Nrf2 Inhibits the Maturation of Murine Dendritic Cells by Ragweed Extract. Am J Respir Cell Mol Biol. 2009 Oct 5.

Singh, A.; Ling, G.; Suhasini, A.N.; Zhang, P.; Yamamoto, M.; Navas-Acien, A.; Cosgrove, G.; Tuder, R.M.; Kensler, T.W.; Watson, W.H.; Biswal, S. Nrf2-dependent sulfiredoxin-1 expression protects against cigarette smoke-induced oxidative stress in lungs. Free Radic Biol Med. 2009 Feb 1;46(3):376-386.

Sussan, T.E.; Rangasamy, T.; Blake, D.J.; Malhotra, D.; El-Haddad, H.; Bedja, D.; Yates, M.S.; Kombairaju, P.; Yamamoto, M.; Liby, K.T.; Sporn, M.B.; Gabrielson, K.L.; Champion, H.C.; Tuder, R.M.; Kensler, T.W.; Biswal, S. Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice. Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):250-255.

Blake, D.J.; Singh, A.; Kombairaju, P.; Malhotra, D.; Mariani, T.J.; Tuder, R.M.; Gabrielson, E.; Biswal, S. Deletion of Keap1 in the lung attenuates acute cigarette smoke-induced oxidative stress and inflammation. Am J Respir Cell Mol Biol. 2010 May;42(5):524-536.

Kong, X.; Thimmulappa, R.; Kombairaju, P.; Biswal, S. NADPH oxidase-dependent reactive oxygen species mediate amplified TLR4 signaling and sepsis-induced mortality in Nrf2-deficient mice. J Immunol. 2010 Jul 1;185(1):569-577.

Malhotra, D.; Portales-Casamar, E.; Singh, A.; Srivastava, S.; Arenillas, D.; Happel, C.; Shyr, C.; Wakabayashi, N.; Kensler, T.W.; Wasserman, W.W.; Biswal, S. Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis. Nucleic Acids Res. 2010 Sep 1;38(17):5718-5734.

Rangasamy, T.; Williams, M.A.; Bauer, S.; Trush, M.A.; Emo, J.; Georas, S.N.; Biswal, S. Nuclear erythroid 2 p45-related factor 2 inhibits the maturation of murine dendritic cells by ragweed extract. Am J Respir Cell Mol Biol. 2010 Sep;43(3):276-285.

Shah, Z.A.; Li, R.C.; Ahmad, A.S.; Kensler, T.W.; Yamamoto, M.; Biswal, S.; Dore, S. The flavanol (-)-epicatechin prevents stroke damage through the Nrf2/HO1 pathway. J Cereb Blood Flow Metab. 2010 Dec;30(12):1951-1961.

Singh, A.; Bodas, M.; Wakabayashi, N.; Bunz, F.; Biswal, S. Gain of Nrf2 function in non-small-cell lung cancer cells confers radioresistance. Antioxid Redox Signal. 2010 Dec 1;13(11):1627-1637.

Singh, A.; Wu, H.; Zhang, P.; Happel, C.; Ma, J.; Biswal, S. Expression of ABCG2 (BCRP) is regulated by Nrf2 in cancer cells that confers side population and chemoresistance phenotype. Mol Cancer Ther. 2010 Aug;9(8):2365-2376.
Singh, U.; Kumar, A.; Sinha, R.; Manral, S.; Arora, S.; Ram, S.; Mishra, R.K.; Gupta, P.; Bansal, S.K.; Prasad, A.K.; Biswal, S.; Parmar, V.S.; Raj, H.G. Calreticulin transacetylase catalyzed modification of the TNF-alpha mediated pathway in the human peripheral blood mononuclear cells by polyphenolic acetates. Chem Biol Interact. 2010 May 14;185(3):263-270.

Solis, L.M.; Behrens, C.; Dong, W.; Suraokar, M.; Ozburn, N.C.; Moran, C.A.; Corvalan, A.H.; Biswal, S.; Swisher, S.G.; Bekele, B.N.; Minna, J.D.; Stewart, D.J.; Wistuba, II. Nrf2 and Keap1 abnormalities in non-small cell lung carcinoma and association with clinicopathologic features. Clin Cancer Res. 2010 Jul 15;16(14):3743-3753.

Wakabayashi, N.; Shin, S.; Slocum, S.L.; Agoston, E.S.; Wakabayashi, J.; Kwak, M.K.; Misra, V.; Biswal, S.; Yamamoto, M.; Kensler, T.W. Regulation of notch1 signaling by nrf2: implications for tissue regeneration. Sci Signal. 2010;3(130):ra52.

Yoshida, T.; Mett, I.; Bhunia, A.K.; Bowman, J.; Perez, M.; Zhang, L.; Gandjeva, A.; Zhen, L.; Chukwueke, U.; Mao, T.; Richter, A.; Brown, E.; Ashush, H.; Notkin, N.; Gelfand, A.; Thimmulappa, R.K.; Rangasamy, T.; Sussan, T.; Cosgrove, G.; Mouded, M.; Shapiro, S.D.; Petrache, I.; Biswal, S.; Feinstein, E.; Tuder, R.M. Rtp801, a suppressor of mTOR signaling, is an essential mediator of cigarette smoke-induced pulmonary injury and emphysema. Nat Med. 2010 Jul;16(7):767-773.

Zhang, P.; Singh, A.; Yegnasubramanian, S.; Esopi, D.; Kombairaju, P.; Bodas, M.; Wu, H.; Bova, S.G.; Biswal, S. Loss of Kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth. Mol Cancer Ther. 2010 Feb;9(2):336-346.


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