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Shyam S. Biswal, PhD

Director, Molecular Mechanisms and Pathophysiology PhD Track

Professor

Departmental Affiliation(s):

Environmental Health Sciences
School of Medicine (Joint)

Center & Institute Affiliation(s):

Molecular Mechanisms and Pathophysiology PhD Track: http://www.jhsph.edu/departments/environmental-health-sciences/degree-programs/phd-in-environmental-disease-molecular-mechanisms-pathophysiology/index.html

Education

PhD , Indian Institute of Technology , 1996
MS , Nagpur University

Honors and Awards

Our laboratory is focused on discovering novel mechanisms of host defense against environmental toxicants that determine immunobiological and pathobiological susceptibility to lung diseases, in order to develop experimental therapeutics for their prevention and intervention among susceptible populations.

We are developing a molecular understanding of the host defense factor Nrf2, which upregulates the stress response transcriptional program and regulates range of pathological processes (oxidative stress, inflammation, and apoptosis) in environmental diseases. We have discovered that there is gain of Nrf2 function, via Keap1 mutation and other mechanisms, in cancers of the lung and other organs. In collaboration with NCATS, the first in class Nrf2 inhibitors are being developed as anti-cancer agents to ameliorate therapeutic resistance of lung and other incurable cancers.

Environmental Health Sciences, cigarette smoke, lung diseases, inflammation, cancer, COPD, emphysema, asthma, environmental stress response

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    1. Kim JH, Thimmulappa RK, Kumar K, Cui W, Kumar S, Kombairaju P, Gaiano N, Zhang H, Margolick J, Matsui W, Macvittie T, Malhotra SV, Biswal S. NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation. J Clin Invest. 2014;3;124(2):730-41.
    2. Singh A, Happel C, Manna SK, Acquaah-Mensah G, Carrerero J, Kumar S, Nasipuri P, Wakabayashi N, Dewi R, Boros LG, Gonzalez FJ, Gabrielson E, Wong KK, Girnun G, Biswal S. Nrf2 regulates miR-1 and miR-206 to drive Tumorigenesis. J Clin Invest. 2013;123 (7) 2921-2934.
    3. Histone deacetylase 6-mediated selective autophagy regulates COPD-associated cilia dysfunction. Lam HC, Cloonan SM, Bhashyam AR, Haspel JA, Singh A, Sathirapongsasuti JF, Cervo M, Yao H, Chung AL, Mizumura K, An CH, Shan B, Franks JM, Haley KJ, Owen CA, Tesfaigzi Y, Washko GR, Quackenbush J, Silverman EK, Rahman I, Kim HP, Mahmood A, Biswal SS, Ryter SW, Choi AM. J Clin Invest. 2013;123(12):5212-30.
    4. Harvey C, Thimmulappa R, Sethi S, Kong X, Yarmus L, Brown R, Feller-Kopman D, Wise R, and Biswal S. (2011) Targeting Nrf2 Signaling Improves Bacterial Clearance by Alveolar Macrophages in Patients with COPD and in a Mouse Model.  Sci Transl Med 3(78):78ra32.
    5. Merchant A, Singh A, Matsui W, and Biswal S. (2011) The redox-sensitive transcription factor, Nrf2, regulates murine hematopoietic stem cell survival independent of ROS levels. Blood. 118:6572-6579.
    6. Wakabayashi N, Shin S, Slocum S, Agoston ES, Wakabayashi J, Kwak MK, Misra V, Biswal S, Yamamoto M, and Kensler TW. (2010) Regulation of Notch1 signaling by Nrf2: implications for tissue regeneration. Sci Signal 3(130):ra52.
    7. Yoshida T, Mett I, Bhunia A, 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, Rangasamy T, Sussan T, Cosgrove G, Mouded M, Shapiro S, Petrache, Biswal S, Feinstein E, and Tuder R. (2010) RTP801, a suppressor of mTOR signaling, is an essential mediator of cigarette smoke induced pulmonary injury and emphysema. Nat Med 16(7):767-73.
    8. Sussan TE, Rangasamy T, Blake DJ, Malhotra D, El-Haddad H, Bedja D, Yates MS, Kombairaju P, Yamamoto M, Liby KT, Sporn MB, Gabrielson KL, Champion HC, Tuder RM, Kensler TW, and Biswal S. (2009) Targeting Nrf2 with the Triterpenoid CDDO-Imidazolide Attenuates Cigarette Smoke-Induced Emphysema and Cardiac Dysfunction in Mice. Proc. Natl Acad Sci. 106(1):250-5.