Charles Vorkas

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Charles.Vorkas@stonybrookmedicine.edu
(631) 444-3490
(631) 444-7518
https://renaissance.stonybrookmedicine.edu/medicine/infectious_diseases/faculty_research/vorkas_lab

Research

Dr. Vorkas is an infectious diseases physician-scientist who focuses on innate lymphocyte immunity during early Mycobacterium tuberculosis (Mtb) infection. Tuberculosis (TB) remains a leading cause of global mortality, yet the immune mechanisms underlying innate resistance or susceptibility to infection remain poorly understood. In order to control the epidemic, fundamental questions of host immunity must be answered, namely (1) why do some individuals highly exposed to Mtb develop infection, while others with similar intensity of exposure, remain uninfected and (2) how do those who develop asymptomatic infection maintain latency or progress to active disease? His laboratory focuses on innate-like T cells that express highly conserved T cell receptors recognizing non-peptide microbial ligands. These cells can execute rapid responses at mucosal surfaces and potentially sterilize infection. During his postdoctoral work, he interrogated a cohort of recently exposed household contacts of active TB patients and discovered that both mucosal-associated invariant T cells (MAIT) and γδ T cells respond to initial tuberculosis infection. Further, he showed that MR1 ligand vaccination resulting in robust enrichment of MAIT cell numbers in murine lung was not sufficient to protect against infection. Ongoing work integrates single cell transcriptional data and flow cytometry to identify unique functional clusters of MAIT cells during homeostasis and activation. Current goals are to identify MAIT, γδ T and Natural Killer Cell clones induced during initial Mtb exposure and infection using systems immunology approaches in human tuberculosis cohorts and mouse models of infection. The overarching goal is to apply these systems biology approaches to identify candidate targets of host-directed immunotherapy against TB disease.

Selected Publications:

Alper, K., Kuzniecky, R., Carlson, C., Barr, W.B., Vorkas, C.K., Patel, J.G., Carrelli, A.L., Starner, K., Flom, P.L., and Devinsky, O. (2008). Postictal psychosis in partial epilepsy: a case-control study. Ann. Neurol. 63(5):602-10. PMID: 18481288.

Vorkas, C.K., Vaamonde, C.M., and Glesby, M.J. (2012). Testosterone replacement therapy and polycythemia in HIVinfected patients. AIDS 26(2):243-5. doi: 10.1097/QAD.0b013e32834db446. PMID: 22008652; PMCID: PMC3670149.

Vorkas, C.K., Tweya, H., Mzinganjira, D., Dickie, G., Weigel, R., Phiri, S., and Hosseinipour, M.C. (2012). Practices to improve identification of adult antiretroviral therapy failure at the Lighthouse Trust clinic in Lilongwe, Malawi. Trop. Med. Int. Health 17(2):169-76. doi: 10.1111/j.1365-3156.2011.02912.x. Epub 2011 Nov 1. PMID: 22039960; PMCID: PMC3294101.

Vorkas,, C.K., Kayira, D., van der Horst, C., Hoffman, I., Hosseinipour, M., Kanyemba, C., Nguluwe, N., Chikaonda, T., Kalikhoka, M., Kalaundi, D., Namarika, D., Gilligan, P., and Krysiak, R. (2012). Tuberculosis drug resistance and outcomes among tuberculosis inpatients in Lilongwe, Malawi. Malawi Med J. 24(2):21-4. PMID: 23638265; PMCID: PMC3588213.

Harrington, B., Vorkas, C.K., Kanyama, C., Ngoma, J., Hoffman, I., and Hosseinipour, M.C. (2015). Altered mental status is an indicator of mortality and associated with both infectious and non-communicable disease in Lilongwe, Malawi. Trop Doct. 45(3):164-7. doi: 10.1177/0049475515577024.

Li, K., Vorkas, C.K., Chaudhry, A., Bell, D., Willis, R., Rudensky, A.. Altman, J., Glickman, M.S., and Aubé, J. (2018). Synthesis, stabilization and characterization of MR1 precursor ligand 5-Amino-6-D-ribitylaminouracil (5-A-RU). PLOS One 13(2):e0191837.

Dupnik, K.M., Bean, J.M., Lee, M.H., Jean Juste, M.A., Skrabanek, L., Rivera, V., Vorkas, C.K., Pape, J.W., Fitzgerald, D.W., and Glickman, M.S. (2018). Blood transcriptomic markers of Mycobacterium tuberculosis load in sputum. Int J Tuberc Lung Dis. 22(8). PMID: 29991407.

Vorkas, C.K., Wipperman, M., Li, K., Aubé, J., Fitzgerald, D., and Glickman, M.S. (2018). Mucosal-associated invariant and gd T cell subsets respond to initial Mycobocterium tuberculosis infection. JCI Insight. 3(19). PMID: 30282828.

Vorkas, C.K., Levy, O., Skular, M., Li, K., Aubé, J., and Glickman, M.S. (2020). Efficient-5-OP-RU-induced enrichment of Mucosal-associated invariant T cells in the murine lung does not enhance control of Mycobacterium tuberculosis infection. Infect Immun. IAI.00524-20. PMID: 33077620.

Rendeiro, A.F., Casano, J., Vorkas, C.K., Singh, H., Morales, A.. DeSimone, R.A., Ellsworth, G.B., Soave, R., Kapadia, S.N., Saito, K., Brown, C.D., Hsu, J., Kyriakides, C., Chui, Cappelli, L., Cacciapuoti, M.T., Tam, W., Galluzzi, L., Simonson, P.D., Elemento, O., Salvatore, M., and Inghirami, G. (2020). Profiling of immune dysfunction in COVID-19 patients allows early prediction of disease progression. Life Sci Alliance. 4(2): e202000955. PMID: 33361110

Wipperman, M.F., Bhatharrai, S.K., Vorkas, C.K., Taur, Y., Mathurin, L., McAulay, K., Vilbrun, S.C., Francois, D.J., Bean, J., Walsh, K.F., Nathan, C., Fitzgerald, D.W., Bucci, V., and Glickman, M.S. (2021). Gastrointestinal microbiota composition predicts peripheral inflammatory state during treatment of human tuberculosis. Nat. Commun.12(1):1141. PMID: 33602926