Thomas J. Braciale

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Primary Appointment

Professor, Pathology

Education

  • BS, Biology, St. Joseph's College, Philadelphia, PA
  • MD, Medicine and Immunology, Univ. of Pennsylvania, Philadelphia, PA
  • PhD, Medicine and Immunology, Univ. of Pennsylvania, Philadelphia, PA
  • Residency, Pathology, Barnes Hospital (Washington Univ.) St. Louis, MO
  • Postdoc, Immunology and Virology, Australian National University, Canberra, Australia

Research Disciplines

Biotechnology, Biotechnology, Cardiovascular Biology, Immunology, Infectious Diseases/Biodefense

Research Interests

T Lymphocyte Responses To Virus Infection

Research Description

My laboratory is interested in the host immune response to virus infection - specifically,we study the role of the adaptive immune response in the clearance of both virus and virus-infected cells from the body, and the contribution of the immune response in producing injury during virus infection. Much of our work focuses on infection of the respiratory tract (the lungs) by two viruses: Influenza virus and Respiratory Syncytial Virus (RSV).
Our research on Influenza focuses on the response of CD8+ T lymphocytes -- Cytolytic T Lymphocytes (CTL) or killer T cells -- to Influenza infection. We want to understand three main things: 1) how CTL are generated during infection; 2) how CD8+ T cells interact with the principal antigen presenting cells of the body (i.e. dendritic cells) to produce those CTL; and 3) how the interplay between Influenza virus and the CTL response contributes to lung injury during infection. We use modern techniques of cell and molecular biology -- including T cell receptor transgenic murine models and virus reverse genetics (to alter the structure of the Influenza genome) in order to understand how specific virus genes (and their products), as well as CTL products (e.g. cytokines) operate to clear infection and/or produce disease. Recently, we have extended this work to include avian influenza virus ("Bird Flu") infection in order to define the mechanisms of lethal infection produced by this virus.
The second virus that we study, RSV, is a major cause of severe lung infection in young infants; and there is currently no safe vaccine for this virus. Immunization with conventional RSV vaccines (e.g. killed virus) results in more severe injury after subsequent natural RSV infection (when compared to natural infection alone). Thus, RSV can induce immune-mediated disease, and can inhibit the normal immune response. Our research in this area is aimed at understanding how this virus can dysregulate the immune response; so safe and effective vaccines can be developed.
In addition to our work in Influenza and RSV, our laboratory has also become involved in Bio-Defense research. Our current project is aimed at the development of new vaccines against the small pox virus when delivered as a weapon of bio-terrorism. We are employing a murine model of small pox infection using the murine equivalent of the virus (i.e. ectromelia or mouse pox virus). We are using innovative methods to clone and express genes from vaccinia virus (the pox virus used to vaccinate humans against small pox) to identify candidate proteins which could serve as the basis for vaccines directed against small pox infection.

Personal Statement

My laboratory is interested in the host immune response to virus infection - specifically,
we study the role of the adaptive immune response in the clearance of both virus
and virus-infected cells from the body, and the contribution of the immune response
in producing injury during virus infection. Much of our work focuses on infection
of the respiratory tract (the lungs) by two viruses: Influenza virus and Respiratory
Syncytial Virus (RSV).
Our research on Influenza focuses on the response of CD8+ T lymphocytes --
Cytolytic T Lymphocytes (CTL) or killer T cells -- to Influenza infection. We
want to understand three main things: 1) how CTL are generated during infection;
2) how CD8+ T cells interact with the principal antigen presenting cells of
the body (i.e. dendritic cells) to produce those CTL; and 3) how the interplay
between Influenza virus and the CTL response contributes to lung injury during
infection. We use modern techniques of cell and molecular biology -- including
T cell receptor transgenic murine models and virus reverse genetics (to alter
the structure of the Influenza genome) in order to understand how specific virus
genes (and their products), as well as CTL products (e.g. cytokines) operate
to clear infection and/or produce disease. Recently, we have extended this work
to include avian influenza virus ("Bird Flu") infection in order to
define the mechanisms of lethal infection produced by this virus.
The second virus that we study, RSV, is a major cause of severe lung infection
in young infants; and there is currently no safe vaccine for this virus. Immunization
with conventional RSV vaccines (e.g. killed virus) results in more severe injury
after subsequent natural RSV infection (when compared to natural infection alone).
Thus, RSV can induce immune-mediated disease, and can inhibit the normal immune
response. Our research in this area is aimed at understanding how this virus
can dysregulate the immune response; so safe and effective vaccines can be developed.
In addition to our work in Influenza and RSV, our laboratory has also become
involved in Bio-Defense research. Our current project is aimed at the development
of new vaccines against the small pox virus when delivered as a weapon of bio-terrorism.
We are employing a murine model of small pox infection using the murine equivalent
of the virus (i.e. ectromelia or mouse pox virus). We are using innovative methods
to clone and express genes from vaccinia virus (the pox virus used to vaccinate
humans against small pox) to identify candidate proteins which could serve as
the basis for vaccines directed against small pox infection.

Training

  • Biodefense & Infectious Diseases Short-Term Training to Increase Diversity in Biomedical Sciences
  • Biotechnology Training Grant
  • Global Biothreats Training Program
  • Interdisciplinary Training Program in Immunology

Selected Publications

2022

Snyder, B. M., Patterson, M. F., Gebretsadik, T., Wu, P., Ding, T., Lee, R. L., . . . Hartert, T. V. (2022). Validation of International Classification of Diseases criteria to identify severe influenza hospitalizations. INFLUENZA AND OTHER RESPIRATORY VIRUSES, 16(3), 371-375. doi:10.1111/irv.12931

Khan, A. R., Misdary, C., Yegya-Raman, N., Kim, S., Narayanan, N., Siddiqui, S., . . . Jabbour, S. K. (2022). Montelukast in hospitalized patients diagnosed with COVID-19. JOURNAL OF ASTHMA, 59(4), 780-786. doi:10.1080/02770903.2021.1881967

Lawrence, M. G., Teague, W. G., Feng, X., Welch, C., Etter, E., Negri, J., . . . Borish, L. (2022). Interleukin-5 receptor alpha (CD125) expression on human blood and lung neutrophils. ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY, 128(1), 53-+. doi:10.1016/j.anai.2021.08.004

2021

Cagnina, R. E., Michels, K. R., Bettina, A. M., Burdick, M. D., Scindia, Y., Zhang, Z., . . . Mehrad, B. (2021). Neutrophil-Derived Tumor Necrosis Factor Drives Fungal Acute Lung Injury in Chronic Granulomatous Disease. JOURNAL OF INFECTIOUS DISEASES, 224(7), 1225-1235. doi:10.1093/infdis/jiab188

Steinke, J. W., Lawrence, M. G., Teague, W. G., Braciale, T. J., Patrie, J. T., & Borish, L. (2021). Bronchoalveolar lavage cytokine patterns in children with severe neutrophilic and paucigranulocytic asthma. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 147(2), 686-+. doi:10.1016/j.jaci.2020.05.039

2020

Mendu, S. K., Stremska, M. E., Schappe, M. S., Moser, E. K., Krupa, J. K., Rogers, J. S., . . . Desai, B. N. (2020). Targeting the ion channel TRPM7 promotes the thymic development of regulatory T cells by promoting IL-2 signaling. SCIENCE SIGNALING, 13(661). doi:10.1126/scisignal.abb0619

Jeong, J. M., Radeos, M. S., Shee, B., Kindschuh, M., Hernandez, C., Sasson, C., . . . Kindschuh, W. (2020). COVID-19 Seroconversion in Emergency Professionals at an Urban Academic Emergency Department in New York City. ANNALS OF EMERGENCY MEDICINE, 76(6), 815-816. doi:10.1016/j.annemergmed.2020.06.038

Somerville, L., Cardani, A., & Braciale, T. J. (2020). Alveolar Macrophages in Influenza A Infection Guarding the Castle with Sleeping Dragons. . Infectious diseases and therapeutics, 1(1). doi:10.31038/idt.2020114

2019

Gorski, S. A., Lawrence, M. G., Hinkelman, A., Spano, M. M., Steinke, J. W., Borish, L., . . . Braciale, T. J. (2019). Expression of IL-5 receptor alpha by murine and human lung neutrophils. PLOS ONE, 14(8). doi:10.1371/journal.pone.0221113

Cheon, I. S., Kim, J. Y., Choi, Y., Shim, B. -S., Choi, J. -A., Jung, D. -I., . . . Chang, J. (2019). Sublingual Immunization With an RSV G Glycoprotein Fragment Primes IL-17-Mediated Immunopathology Upon Respiratory Syncytial Virus Infection. FRONTIERS IN IMMUNOLOGY, 10. doi:10.3389/fimmu.2019.00567

Teague, W. G., Lawrence, M. G., Shirley, D. -A. T., Garrod, A. S., Early, S. V., Payne, J. B., . . . Borish, L. (2019). Lung Lavage Granulocyte Patterns and Clinical Phenotypes in Children with Severe, Therapy-Resistant Asthma. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, 7(6), 1803-+. doi:10.1016/j.jaip.2018.12.027

2017

Cronk, J. C., Herz, J., Kim, T. S., Louveau, A., Moser, E. K., Sharma, A. K., . . . Kipnis, J. (2017). Influenza A induces dysfunctional immunity and death in MeCP2-overexpressing mice. JCI INSIGHT, 2(2). doi:10.1172/jci.insight.88257

Cardani, A., Boulton, A., Kim, T. S., & Braciale, T. J. (2017). Alveolar Macrophages Prevent Lethal Influenza Pneumonia By Inhibiting Infection Of Type-1 Alveolar Epithelial Cells. PLOS PATHOGENS, 13(1). doi:10.1371/journal.ppat.1006140

2016

Jiang, L., Yao, S., Huang, S., Wright, J., Braciale, T. J., & Sun, J. (2016). Type I IFN signaling facilitates the development of IL-10-producing effector CD8(+) T cells during murine influenza virus infection. EUROPEAN JOURNAL OF IMMUNOLOGY, 46(12), 2778-2788. doi:10.1002/eji.201646548

Newton, A. H., Cardani, A., & Braciale, T. J. (2016). The host immune response in respiratory virus infection: balancing virus clearance and immunopathology. SEMINARS IN IMMUNOPATHOLOGY, 38(4), 471-482. doi:10.1007/s00281-016-0558-0

Adamson, S. E., Griffiths, R., Moravec, R., Senthivinayagam, S., Montgomery, G., Chen, W., . . . Leitinger, N. (2016). Disabled homolog 2 controls macrophage phenotypic polarization and adipose tissue inflammation. JOURNAL OF CLINICAL INVESTIGATION, 126(4), 1311-1322. doi:10.1172/JCI79590

2015

Kim, T. S., Hanak, M., Trampont, P. C., & Braciale, T. J. (2015). Stress-associated erythropoiesis initiation is regulated by type 1 conventional dendritic cells. JOURNAL OF CLINICAL INVESTIGATION, 125(10), 3965-3980. doi:10.1172/JCI81919

Yao, S., Jiang, L., Moser, E. K., Jewett, L. B., Wright, J., Du, J., . . . Sun, J. (2015). Control of pathogenic effector T-cell activities in situ by PD-L1 expression on respiratory inflammatory dendritic cells during respiratory syncytial virus infection. MUCOSAL IMMUNOLOGY, 8(4), 746-759. doi:10.1038/mi.2014.106

Moser, E. K., Sun, J., Kim, T. S., & Braciale, T. J. (2015). IL-21R Signaling Suppresses IL-17(+) Gamma Delta T Cell Responses and Production of IL-17 Related Cytokines in the Lung at Steady State and After Influenza A Virus Infection. PLOS ONE, 10(4). doi:10.1371/journal.pone.0120169

Krueger, P. D., Kim, T. S., Sung, S. -S. J., Braciale, T. J., & Hahn, Y. S. (2015). Liver-Resident CD103(+) Dendritic Cells Prime Antiviral CD8(+) T Cells In Situ. JOURNAL OF IMMUNOLOGY, 194(7), 3213-3222. doi:10.4049/jimmunol.1402622

Steinke, J. W., Liu, L., Turner, R. B., Braciale, T. J., & Borish, L. (2015). Immune Surveillance by Rhinovirus-Specific Circulating CD4(+) and CD8(+) T Lymphocytes. PLOS ONE, 10(1). doi:10.1371/journal.pone.0115271

Hufford, M. M., Kim, T. S., Sun, J., & Braciale, T. J. (2015). The Effector T Cell Response to Influenza Infection. INFLUENZA PATHOGENESIS AND CONTROL - VOL II, 386, 423-455. doi:10.1007/82_2014_397

2014

Yoo, J. -K., & Braciale, T. J. (2014). IL-21 Promotes Late Activator APC-Mediated T Follicular Helper Cell Differentiation in Experimental Pulmonary Virus Infection. PLOS ONE, 9(9). doi:10.1371/journal.pone.0105872

Braciale, T., & Kim, T. (2014). Influenza pathogenesis: Club cells take the "cure". JOURNAL OF EXPERIMENTAL MEDICINE, 211(9), 1705. doi:10.1084/jem.2119insight2

Buckley, M. W., Arandjelovic, S., Trampont, P. C., Kim, T. S., Braciale, T. J., & Ravichandran, K. S. (2014). Unexpected Phenotype of Mice Lacking Shcbp1, a Protein Induced during T Cell Proliferation. PLOS ONE, 9(8). doi:10.1371/journal.pone.0105576

Moser, E. K., Hufford, M. M., & Braciale, T. J. (2014). Late Engagement of CD86 after Influenza Virus Clearance Promotes Recovery in a FoxP3(+) Regulatory T Cell Dependent Manner. PLOS PATHOGENS, 10(8). doi:10.1371/journal.ppat.1004315

Dolina, J. S., Braciale, T. J., & Hahn, Y. S. (2014). Liver-Primed CD8(+) T Cells Suppress Antiviral Adaptive Immunity Through Galectin-9-Independent T-Cell Immunoglobulin and Mucin 3 Engagement of High-Mobility Group Box 1 in Mice. HEPATOLOGY, 59(4), 1351-1365. doi:10.1002/hep.26938

2013

Yoo, J. -K., Kim, T. S., Hufford, M. M., & Braciale, T. J. (2013). Viral infection of the lung: Host response and sequelae. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 132(6), 1263-1276. doi:10.1016/j.jaci.2013.06.006

Hua, L., Yao, S., Pham, D., Jiang, L., Wright, J., Sawant, D., . . . Sun, J. (2013). Cytokine-Dependent Induction of CD4(+) T cells with Cytotoxic Potential during Influenza Virus Infection. JOURNAL OF VIROLOGY, 87(21), 11884-11893. doi:10.1128/JVI.01461-13

Braciale, T. J., & Hahn, Y. S. (2013). Immunity to viruses. IMMUNOLOGICAL REVIEWS, 255(1), 5-12. doi:10.1111/imr.12109

Gorski, S. A., Hahn, Y. S., & Braciale, T. J. (2013). Group 2 Innate Lymphoid Cell Production of IL-5 Is Regulated by NKT Cells during Influenza Virus Infection. PLOS PATHOGENS, 9(9). doi:10.1371/journal.ppat.1003615

Sun, J., & Braciale, T. J. (2013). Role of T cell immunity in recovery from influenza virus infection. CURRENT OPINION IN VIROLOGY, 3(4), 425-429. doi:10.1016/j.coviro.2013.05.001

Kim, T., Gorski, S., Hahn, S., & Braciale, T. (2013). Distinct dendritic cell subsets dictate the fate decision between effector and memory CD8+T cell differentiation. JOURNAL OF IMMUNOLOGY, 190. Retrieved from https://www.webofscience.com/

Varga, S. M., & Braciale, T. J. (2013). The Adaptive Immune Response to Respiratory Syncytial Virus. CHALLENGES AND OPPORTUNITIES FOR RESPIRATORY SYNCYTIAL VIRUS VACCINES, 372, 155-171. doi:10.1007/978-3-642-38919-1_8

2012

Hufford, M. M., Richardson, G., Zhou, H., Manicassamy, B., Garcia-Sastre, A., Enelow, R. I., & Braciale, T. J. (2012). Influenza-Infected Neutrophils within the Infected Lungs Act as Antigen Presenting Cells for Anti-Viral CD8(+) T Cells. PLOS ONE, 7(10). doi:10.1371/journal.pone.0046581

Yoo, J. -K., Fish, E. N., & Braciale, T. J. (2012). LAPCs promote follicular helper T cell differentiation of Ag-primed CD4(+) T cells during respiratory virus infection. JOURNAL OF EXPERIMENTAL MEDICINE, 209(10), 1853-1867. doi:10.1084/jem.20112256

Gorski, S. A., Hufford, M. M., & Braciale, T. J. (2012). Recent insights into pulmonary repair following virus-induced inflammation of the respiratory tract. CURRENT OPINION IN VIROLOGY, 2(3), 233-241. doi:10.1016/j.coviro.2012.04.006

Kennedy, J. L., Turner, R. B., Braciale, T., Heymann, P. W., & Borish, L. (2012). Pathogenesis of rhinovirus infection. CURRENT OPINION IN VIROLOGY, 2(3), 287-293. doi:10.1016/j.coviro.2012.03.008

Braciale, T. J., Sun, J., & Kim, T. S. (2012). Regulating the adaptive immune response to respiratory virus infection. NATURE REVIEWS IMMUNOLOGY, 12(4), 295-305. doi:10.1038/nri3166

2011

Braciale, T. J., & Kim, T. S. (2011). Slowing down with age: lung DCs do it too. JOURNAL OF CLINICAL INVESTIGATION, 121(12), 4636-4639. doi:10.1172/JCI61367

Hargadon, K. M., Zhou, H., Albrecht, R. A., Dodd, H. A., Garcia-Sastre, A., & Braciale, T. J. (2011). Major Histocompatibility Complex Class II Expression and Hemagglutinin Subtype Influence the Infectivity of Type A Influenza Virus for Respiratory Dendritic Cells. JOURNAL OF VIROLOGY, 85(22), 11955-11963. doi:10.1128/JVI.05830-11

Sun, J., Cardani, A., Sharma, A. K., Laubach, V. E., Jack, R. S., Mueller, W., & Braciale, T. J. (2011). Autocrine Regulation of Pulmonary Inflammation by Effector T-Cell Derived IL-10 during Infection with Respiratory Syncytial Virus. PLOS PATHOGENS, 7(8). doi:10.1371/journal.ppat.1002173

Kim, T. S., Sun, J., & Braciale, T. J. (2011). T cell responses during influenza infection: getting and keeping control. TRENDS IN IMMUNOLOGY, 32(5), 225-231. doi:10.1016/j.it.2011.02.006

Sun, J., Dodd, H., Moser, E. K., Sharma, R., & Braciale, T. J. (2011). CD4(+) T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs. NATURE IMMUNOLOGY, 12(4), 327-U80. doi:10.1038/ni.1996

Hufford, M. M., Kim, T. S., Sun, J., & Braciale, T. J. (2011). Antiviral CD8(+) T cell effector activities in situ are regulated by target cell type. JOURNAL OF EXPERIMENTAL MEDICINE, 208(1), 167-180. doi:10.1084/jem.20101850

2010

Yoon, H., Kim, T. S., & Braciale, T. J. (2010). The Cell Cycle Time of CD8(+) T Cells Responding In Vivo Is Controlled by the Type of Antigenic Stimulus. PLOS ONE, 5(11). doi:10.1371/journal.pone.0015423

Kim, T. S., Hufford, M. M., Sun, J., Fu, Y. -X., & Braciale, T. J. (2010). Antigen persistence and the control of local T cell memory by migrant respiratory dendritic cells after acute virus infection. JOURNAL OF EXPERIMENTAL MEDICINE, 207(6), 1161-1172. doi:10.1084/jem.20092017

Ream, R. M., Sun, J., & Braciale, T. J. (2010). Stimulation of Naive CD8(+) T Cells by a Variant Viral Epitope Induces Activation and Enhanced Apoptosis. JOURNAL OF IMMUNOLOGY, 184(5), 2401-2409. doi:10.4049/jimmunol.0902448