Contact

Department

Disease Intervention & Prevention (DIP) Program; Core Scientist SNPRC, Texas Biomedical Research Institute

Mehra, Smriti, Ph.D.

Adjunct Associate Professor

Personal Statement:

Smriti Mehra, Ph.D., is a molecular and microbiologist seeking to understand basic mechanisms of tuberculosis (TB) infection, and develop new vaccines and therapies that can stop this infectious disease. She specifically studies how TB evades the body’s immune system, hiding in the lungs often for decades, before becoming active and causing serious illness. She also studies active TB and interactions between TB and HIV.

The lab leverages the nonhuman primate (NHP) model of TB based on infecting rhesus macaques with infectious aerosols of Mycobacterium tuberculosis (Mtb). We have since refined our model to be able to study LTBI, active TB and HIV-induced reactivation using SIV as a surrogate. My program focuses on immune responses in-vivo, particularly the negative regulation of anti-Mtb immunity in the context of the granuloma, using IDO, PD-1 and LAG3 as examples in the macaque model, both in the setting of active TB infection as well as in the setting of Mtb/HIV co-infection. I am studying if these pathways can be targeted in a host-directed manner adjunctive to chemotherapy for treatment. I am also leveraging the macaque model to study correlates of protective immunity and vaccine efficacy, especially focusing on CD4+ T cells. Of particular interest is the comparative evaluation of lung CD4+ T cell responses elicited by novel whole-cell Mtb vaccine candidates and standard vaccine BCG.

Education

1990-B.Sc. (Honors), University of Delhi -Biochemistry
1991-Diplomat (Biotechnol), University of Delhi -Biotechnology
1993-M.Sc., University of Delhi -Biochemistry
2002-Ph.D., University of Delhi -Genetics

Research

Inside the Lab
A key area of of my research is the role played by immune checkpoint inhibitors, such as IDO-1, LAG-3 and CTLA-4, in modulating responses to Mycobacterium tuberculosis (Mtb), the bacterium that causes TB. My lab is testing several host-directed therapies to inhibit the IDO pathway to see if it that can help fight off TB infection. Inhibiting this pathway has helped cancer patients, by improving the body’s immune response and shrink tumors.

We are also studying CD4+ T cells and their response to the only approved TB vaccine, BCG, versus new whole-cell vaccine candidates. I am also interested in developing and testing new recombinant BCG vaccines for their efficacy against TB.

Main Technologies and Methods Used
Macrophage biology
Confocal microscopy
Flow cytometry
Transcriptomics including RNAseq
Bacteriology

Awards & Accomplishments

Awards/accomplishments:

2009        Recipient of the Beginning Scientist Award by Tulane Center for Infectious Diseases.

2012        Recipient of the Young Scientist Award at the Annual NHP Models of AIDS Meeting in New Orleans, LA – Oral Presentation.

2012        Session Chair – Post-doctoral Fellows Session, First Louisiana Tuberculosis Symposium, Covington, LA (Apr 19-20th, 2012)

Lab Members

Dr. Bindu Singh   –Post Doctoral fellow

Kendall Asher       –Research technician

Publications

Complete list of publications:

https://www.ncbi.nlm.nih.gov/myncbi/1pmVQ0tXZugk5/bibliography/public/?sortby=pubDate&sdirection=descending

Published in 2021-2022

  1. Sharan R, Ganatra SR, Bucsan AN, Cole J, Singh DK, Alvarez X, Gough M, Alvarez C, Blakley A, Ferdin J, Thippeshappa R, Singh B, Escobedo R, Shivanna V, Dick EJ, Jr., Hall-Ursone S, Khader SA, Mehra S, Rengarajan J, Kaushal D. 2022. Antiretroviral therapy timing impacts latent tuberculosis infection reactivation in a Mycobacterium tuberculosis/SIV coinfection model. Journal of Clinical Investigation 132(3). PMID: 34855621 PMCID: PMC880332.
  2. McCaffrey EF, Donato M, Keren L, Chen Z, Delmastro A, Fitzpatrick MB, Gupta S, Greenwald NF, Baranski A, Graf W, Kumar R, Bosse M, Fullaway CC, Ramdial PK, Forgó E, Jojic V, Van Valen D, Mehra S, Khader SA, Bendall SC, van de Rijn M, Kalman D, Kaushal D, Hunter RL, Banaei N, Steyn AJC, Khatri P, Angelo M. 2022. The immunoregulatory landscape of human tuberculosis granulomas. Nature Immunology;23(2):318-329. PMID: 35058616 PMCID: PMC8810384.
  3. Bucşan AN, Veatch AV, Singh DK, Akter S, Golden NA, Kirkpatrick M, Threeton B, Ahmed M, Doyle LA, Russell-Lodrigue K, Norton EB, Didier PJ, Roy CJ, Abramovitch RB, Mehra S, Khader SA, Kaushal D. 2022. Response to hypoxia and the ensuing dysregulation of inflammation impacts Mycobacterium tuberculosisAmerican Journal of Respiratory Critical Care Medicine.  Jul 1;206(1):94-104. PMID: 35412961.
  4. Sharan R, Ganatra SR, Singh DK, JCole J, Foreman TW, Thippeshappa R,. Peloquin CA, Shivanna V, Gonzalez O, Day CL, Gandhi N, Dick, Jr EJ, Hall-Ursone S, Mehra S, Schlesinger LS, Rengarajan J, Kaushal 2022. Isoniazid and Rifapentine Treatment effectively reduces persistent M. tuberculosis infection in macaque lungs. Journal of Clinical Investigation. Jul 21:e161564. doi: 10.1172/JCI161564. PMID: 35862216.
  5. Gough M, Singh DS, Golden NA, Niu T, Kaushal D, Mehra S. 2022. Macrophage-expressed and peripheral blood markers predict the onset of active TB, distinguish from LTBI and correlate with lung disease measures. Pathogens. 11, 544.https://doi.org/10.3390 11050544.
  6. Gough M, Singh DS, Golden NA, Niu T, Kaushal D, Mehra S. 2022. System-wide identification of myeloid markers of TB disease and HIV-induced reactivation. Frontiers in Immunology. Accepted.
  7. Singh B, Singh DK, Ganatra SR, Escobedo RA, Khader S, Schlesinger LS, Kaushal D, Mehra S. 2021. Myeloid-Derived Suppressor Cells Mediate T Cell Dysfunction in Nonhuman Primate TB Granulomas. mBio.12(6):e0318921.
  8. Cronan MR, Hughes EJ, Brewer WJ, Viswanathan G, Hunt EG, Singh B, Mehra S, Oehlers SH, Gregory SG, Kaushal D, Tobin DM. 2021. A non-canonical type 2 immune response coordinates tuberculous granuloma formation and epithelialization. Cell.184(7):1757-74.
  9. Esaulova E, Das S, Singh DK, Choreno-Parra JA, Swain A, Arthur L, Rangel-Moreno J, Ahmed M, Singh B, Gupta A, Fernandez-Lopez LA, de la Luz Garcia-Hernandez M, Bucsan A, Moodley C, Mehra S, Garcia-Latorre E, Zuniga J, Atkinson J, Kaushal D, Artyomov MN, Khader SA. 2021. The immune landscape in tuberculosis reveals populations linked to disease and latency. Cell Host Microbe. 29(2):165-78 e8.
  10. Irvine EB, O’Neil A, Darrah PA, Shin S, Choudhary A, Li W, Honnen W, Mehra S, Kaushal D, Gideon HP, Flynn JL, Roederer M, Seder RA, Pinter A, Fortune S, Alter G. 2021. Robust IgM responses following intravenous vaccination with Bacille Calmette-Guerin associate with prevention of Mycobacterium tuberculosis infection in macaques. Nature Immunology. 22(12):1515-23.
  11. Willemse D, Moodley C, Mehra S, Kaushal D. 2021. Transcriptional Response of Mycobacterium tuberculosis to Cigarette Smoke Condensate. Frontiers in Microbiology. 12:744800.
  12. Singh DK, Aladyeva E, Das S, Singh B, Esaulova E, Swain A, Ahmed M, Cole J, Moodley C, Mehra S, Larry Schlesinger L, Artyomov M, Khader S, Kaushal D. Myeloid cell interferon responses correlate with clearance of SARS-CoV-2 Nature Communications. In press.
  13. Wang X, Mehra S, Kaushal D, Veazey RS, Xu H. 2021. Abnormal Tryptophan Metabolism in HIV and Mycobacterium tuberculosis Frontiers in Microbiology. 12:666227.

 

  1. Published in 2019-2020
  2. Bucşan AN, Chatterjee A, Singh DK, Foreman TW, Lee T-H, Ahmed MA, Threeton B, Kirkpatrick MG, Golden NA, Alvarez X, Hoxie JA, Mehra S, Rengarajan J, Khader SA, Kaushal D. Mechanisms of reactivation of latent tuberculosis infection due to SIV co-infection. Journal of Clinical Investigation.;129(12):5254-5260. PMID: 31479428.
  3. Bucşan AN, Mehra S, Khader SA, Kaushal D. 2019.The Current state of genomic approaches and animal models for identifying and validating molecular determinants of infection and disease. Pathogens and Diseases. 2019 Jun 1;77(4). pii: ftz037. PMID: 31381766.
  4. Gautam US, Mehra S, Alvarez X, Niu T, Tyagi JS and Kaushal D. 2019. Mycobacterium tuberculosis Sensor Kinase DosS Modulates the Autophagosome in a DosR-independent Manner. Communications Biology.Sep 20;2(1):349. doi: 10.1038/s42003-019-0594-0. PMCID: PMC6754383.
  5. Sharan R, Bucşan AN, Ganatra SR, Paiardini M, Mohan M, Mehra S, Khader S, Kaushal D. 2020. Chronic immune activation in TB/HIV co-infection. Trends in Microbiology. May 29:S0966-842X(20)30132-3. PMID: 32417227.
  6. Coskun F, Srivastava S, Raj P, Dozmorov I, Belkaya S, Mehra S, Golden NA, Bucşan AN, Chapagain ML, Wakeland EK, Kaushal D, Gumbo T, van Oers NSC. 2020. SncRNA-1 is a small noncoding RNA produced by Mycobacterium tuberculosis in infected cells that positively regulates genes coupled to oleic acid biosynthesis. Frontiers in Microbiology. 2020 Jul 28;11:1631. doi: 10.3389/fmicb.2020.01631. eCollection PMID: 32849337. PMCID: PMC7399025.
  7. Ganatra SR, Bucşan AN, Alvarez X, Kumar S, Chatterjee A,Quezada M, Fish A, Singh DK, Singh B, Sharan R, Lee T, Shanmughasundaram U, Velu V, Khader SA, Mehra S, Rengarajan J, Kaushal D. 2020. Anti-retroviral therapy does not reduce tuberculosis reactivation in a tuberculosis-HIV co-infection model. Journal of Clinical Investigation. Oct 1;130(10):5171-5179. doi: 10.1172/JCI136502.
  8. Choreño-Parra A, Bobba S, Rangel-Moreno J, Ahmed M, Mehra S, Rosa B, Martin J, Mitreva M, Kaushal D, Zuñiga J, Khader SA. 2020. Mycobacterium tuberculosis HN878 infection induces human-like B cell follicles in mice. Journal of Infectious Diseases. 221(10):1636-1646. PMID: 31832640. PMCID: PMC7184917.
  9. Scott NR, Al-Hammadi N, Domingo-Gonzalez R, Bucşan AN, Rangel-Moreno J, Thomas K, Treerat P, Cruz-Lagunas A, Alvarez LAJ, Mehra S, Vogl T, Kaushal D, Scriba TS, Zuniga J, Khader S. 2020. S100A8/9 proteins regulate neutrophil recruitment during chronic tuberculosis. Journal of Clinical Investigation. 130(6):3098-3112. PMID: 32134742. PMCID: PMC7259997.
  10. Ahmed M, Thirunavukkarasu S, Rosa BA, Thomas KA, Das S, Rangel-Moreno J, Lu L, Mehra S, Mbandi SK, Thackray LB, Diamond MS, Murphy KM, Means T, Martin J, Kaushal D, Scriba TJ, Mitreva M, Khader SA. Immune correlates of tuberculosis disease and risk translate across species. Science Translational Medicine. Jan 29; 12(528). pii: eaay0233. doi: 10.1126/scitranslmed.aay0233. PMID: 31996462.

 

  1. Published in 2018
  2. Vashistha H, Marrero L, Reiss K, Cohen A, Malhotra A, Javed T, Bradley A, Abbruscato F, Giusti S, Jimenez A, Mehra S, Kaushal D, Giorgio M, Pelicci PG, Kakoki K, Singhal P, Bunnell B, and Meggs B. Aging phenotype(s) in kidneys of diabetic mice are p66ShcA dependent. American Journal of Physiology (Renal).2018 Dec 1;315(6):F1833-F1842. PMID: 30207172. PMCID: PMC6336986.
  3. Kuroda MJ, Sugimoto C, Cai Y, Merino KM, Mehra S, Arainga MA, Midkiff CC, Alvarez-Hernandez X, Didier ES, Kaushal D. High Turnover of Tissue Macrophages Contributes to TB Reactivation in SIV-infected Rhesus Macaques. J Infect Dis 2018 May 25;217(12):1865-1874. PMCID: PMC5972562.
  4. Gautam US, Bucsan AN, Foreman TW, Veatch AV, Gentry KM, Golden NA, Alvarez X, Adekambi T, Doyle-Myers LA, Russell-Lodrigue KE, Didier PJ, Kousoulas KG, Kalman D, Lackner AA, Rengarajan J, Khader SA, Kaushal D, Mehra S. In vivo Inhibition of tryptophan catabolism reorganizes the tuberculoma and augments immune-mediated control of Mycobacterium tuberculosis. PNAS. 2018 Jan; 115(1): E62-E71.
  5. Foreman TW, Veatch AV, LoBato DN, Didier PJ, Doyle-Meyers LA, Russell-Lodrigue KE, Lackner AA, K. Gus Kousoulas, Khader SA, Kaushal D*, Mehra S*. Non-pathological infection of macaques by an attenuated mycobacterial vaccine is not reactivated in the setting of HIV coinfection. Am J Pathol. (*co-corresponding author). 187(12):2811-2820. PMID: 28935575. PMCID: PMC5718104.
  6. Phillips BL, Gautam US, Bucsan AN, Foreman TW, Golden NA, Niu T, Kaushal D, Mehra S. LAG-3 potentiates the survival of Mycobacterium tuberculosis in host phagocytes by modulating mitochondrial signaling in an in-vitro granuloma model. PLoS ONE. 12:e0180413. PMID: 28880895. PMCID: PMC5589099.
  7. Foreman TW, Mehra S, Lackner AA, Kaushal D. Translational research in the nonhuman primate model of tuberculosis. Institute for Laboratory Animal Research Journal. May 31:1-9. PMID: PMID: 28575319. PMCID: PMC6279141.