Current projects are focused on the innate immune response to tuberculosis and leprosy. The goal of this research is to identify immune mechanisms that make certain populations more or less susceptible to severe disease phenotypes than others.
To this end, the Shah Lab has identified polymorphisms in a critical stress response gene, TOLLIP, that alters the cytokine response within macrophages that impact the innate immune response and TB susceptibility in human populations. Our lab is dedicated to pursuing how these genes and others like them influence TB pathogenesis using a combination of human population-based methods and mouse knockout studies.
To complement these population-based studies, the lab uses genetic editing of cell lines and primary cells as well as molecular biology techniques to pinpoint polymorphisms of interest. The goal of these studies is to determine critical molecular pathways that may be novel targets for therapeutic intervention.
Dr. Javeed Shah is an affiliate member of the Center for Innate Immunity and Immune Disease (CIIID).
TOLLIP deficiency is associated with increased resistance to Legionella pneumophila pneumonia. Shah JA, Emery R, Lee B, Venkatasubramanian S, Simmons JD, Brown M, Hung CF, Prins JM, Verbon A, Hawn TR, Skerrett, SJ. Mucosal Immunol. 2019. In press.
A Functional Toll-Interacting Protein Variant Is Associated with Bacillus Calmette-Guérin-Specific Immune Responses and Tuberculosis. Shah JA, Musvosvi M, Shey M, Horne DJ, Wells RD, Peterson GJ, Cox JS, Daya M, Hoal EG, Lin L, Gottardo R, Hanekom WA, Scriba TJ, Hatherill M, Hawn TR. Am J Respir Crit Care Med. 2017 Aug 15;196(4):502-511. doi: 10.1164/rccm.201611-2346OC.
Genetic Variation in Toll-Interacting Protein Is Associated With Leprosy Susceptibility and Cutaneous Expression of Interleukin 1 Receptor Antagonist. Shah JA, Berrington WR, Vary JC Jr, Wells RD, Peterson GJ, Kunwar CB, Khadge S, Hagge DA, Hawn TR. J Infect Dis. 2016 Apr 1;213(7):1189-97. doi: 10.1093/infdis/jiv570. Epub 2015 Nov 26.
Human TOLLIP regulates TLR2 and TLR4 signaling and its polymorphisms are associated with susceptibility to tuberculosis. Shah JA, Vary JC, Chau TT, Bang ND, Yen NT, Farrar JJ, Dunstan SJ, Hawn TR. J Immunol. 2012 Aug 15;189(4):1737-46. doi: 10.4049/jimmunol.1103541. Epub 2012 Jul 9.
Dendritic cells are responsible for the capacity of CpG oligodeoxynucleotides to act as an adjuvant for protective vaccine immunity against Leishmania major in mice. Shah JA, Darrah PA, Ambrozak DR, Turon TN, Mendez S, Kirman J, Wu CY, Glaichenhaus N, Seder RA. J Exp Med. 2003 Jul 21;198(2):281-91.