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Joshy Jacob, Ph.D.

Visiting Faculty

jjacob3@emory.edu

joshy
  • Profile

    • 1994-98: Post-Doc(Immunology),Massachusetts Institute of Technology, MA
    • 1992-94: Post-Doc(Immunology),Rockefeller University, New York, NY
    • 1992: Ph.D(Immunology),University of Maryland, Baltimore, MD
    • 1986: BS (Medical Technology),University of Texas-Pan American, Edinburg, TX
    • 2009-2012: Associate Director, Emory / UGA Influenza Pathogenesis and Immunology Research Center
    • 2007-present: Tenured Associate Professor, Department of Microbiology & Immunology, Emory University, Atlanta
    • 1999-present: Member, Emory Vaccine Center, Emory University, Atlanta, GA
    • 1999-present: Affiliate Scientist, Yerkes National Primate Center, Emory University, Atlanta, GA
    • 1999-2007: Assistant Professor, Dept of Microbiology & Immunology, Emory University, Atlanta
    • 1994-1998: Postdoctoral Fellow, Dr. David Baltimore Laboratory, M.I.T, Cambridge, MA
    • 1992-1994: Postdoctoral Fellow, Dr. David Baltimore Laboratory, Rockefeller University, NY
    • 1991: Visiting Scientist, Dr. Klaus Rajewsky Laboratory, University of Cologne, Germany
    • 1987-1992: Research Assistant, Garnett Kelsoe Laboratory, University of Maryland, Baltimore, MD
    • 2012: present Section Editor, Journal of Immunology
    • 2005-2010: American Cancer Society Research Scholar
    • 2004: Dean’s Excellence in Teaching Award, Emory University
    • 1996–1999: Special Fellow of the Leukemia Society of America
    • 1993-1996: Helen Hay Whitney Postdoctoral Fellow
    • 1986: BS, Summa cum laude
  • Research

    As Visiting Faculty at RGCB, I am a joint Principal Investigator on two research programs in Viral Disease Biology. The first one is studying the dynamics of immune responses to influenza vaccine. Influenza is the most recurring respiratory disease in humans. During the 20th century, Influenza A viruses have afflicted the human race with three pandemics in 1918, 1957 and 1968 and numerous seasonal epidemics. While most people recover from infection, some develop life-threatening complications such as pneumonia. This occurs predominantly in the elderly (>65 years of age), people with chronic medical conditions such as asthma, diabetes, or heart disease, pregnant women, and young children of 0.5-5 years of age. Although a single influenza infection provides lifelong immunity against the homotypic strain, new variants continue to emerge, rendering the public susceptible to infection with a novel flu variant. This is because the virus constantly undergoes genetic variation to avoid the protective immunity of the host. This form of antigenic variation of influenza virus is called antigenic drift and occurs mainly to two surface glycoproteins of the virus, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift leads to seasonal influenza infections. Significantly more drastic antigenic variation occurring in influenza viruses is called antigenic shift. Antigenic shift occurs via antigenic reassortment between two different strains of influenza viruses. Once this virus acquires transmissibility among the human population, the results can be a devastating pandemic. Due to continuous antigenic variations and as an effort to minimize the death toll related to influenza virus, in the West annual flu vaccinations are recommended, especially for high-risk groups, which include the elderly and immune-compromised patients. In India, annual flu vaccinations are almost never administered and hence pre-existing serological memory to influenza viruses is almost exclusively acquired due to natural infections. This gives us a unique opportunity to study evolution of influenza viruses, and human immune responses to natural infections, uncomplicated by immune responses to vaccinations. In collaboration with Dr. Rick Kennedy from the Mayo Clinic, Rochester, MN, USA and Professor M. Radhakrishna Pillai from RGCB, we propose three specific aims, namely (1) To identify influenza viruses that circulated in Kerala from 2009- 2012 and study virus evolution in the absence of deliberate vaccination, (2) To determine the extent of serum cross reactivity in an unvaccinated human population and (3) To generate monoclonal antibodies from unvaccinated human population and map their binding to globular head vs stalk regions of hemagglutinin. The proposed work is significant because it will give us crucial insight into the potential downside (or upside) of not have an active annual influenza vaccination program in India.

    The second project I am involved in at RGCB is on understanding measles vaccine failure (and success) in Kerala. This is also a joint collaborative project with Dr Rick Kenndey from the Mayo Clinic and Professor Radhakrishna Pillai and Dr Vijesh Sreedhar from RGCB. Measles is a global public health problem, being one of the top causes of death in children worldwide. Measles remains endemic in parts of the world such as Africa and Southeast Asia, and imported cases continue to outbreaks affecting tens of thousands of individuals, even in regions that had previously controlled or eliminated the disease. Measles vaccination began in India in the 1980s and the 2-dose schedule was introduced in 2010. Despite these vaccination campaigns and rising rates of vaccine coverage, India experiences hundreds of outbreaks yearly. In 2005, 92,000 children died from measles in India, and in 2010 that number had dropped to ~65,000, but still accounts for nearly half of all global measles mortality. Measles vaccine (MV) failure clearly plays a role in the global outbreaks, where between 10-50% of cases occurred in individuals who had been previously immunized. In India, vaccine failure is an even greater problem as seroprotection rates < 75% have been documented. Our objective is to better understand immunological dynamics of measles vaccine failure southern India.

    ACTIVE

    1R01AI100110-01 (Jacob)
    NIH/NIAID
    08/15/2012 – 08/14/2015
    Title: Overcoming maternal antibody-mediated suppression of infant immune responses

    The major goal of this project is to overcome immune suppression of infant immunity by maternal antibodies. Overlap: None

    1R56AI095712-01A1 (Jacob)
    NIH/NIAID
    08/15/2012 – 08/14/2014
    Title: Regulation of plasma cell longevity by CD28-B7 pathway

    The major goal of this project is to understand how CD28 and B7 molecules regulate plasma cells.
    Overlap: None

    HHSN266200700006C (Compans PI; Jacob Project Leader)
    04/01/2007 – 03/30/2014
    NIH/NIAID Influenza Center of Excellence for Research and Surveillance
    B cell memory & original antigenic sin

    The goal of this project is to study original antigenic sin responses to influenza viruses.

    COMPLETED

    RSG-05-144-01-LIB (Jacob)
    07/01/2005 – 06/31/2010
    American Cancer Society
    Title: B Cell Memory
    Role: Principal Investigator

    The goal of this project was to understand how B cell memory is generated.

  • Publications

    1. Joshy Jacob, Garnett Kelsoe, Klaus Rajewsky and Ursula Weiss. 1991. Intraclonal generation of antibody mutants in germinal centers. Nature 354:389-392. PMID: 1956400
    2. Joshy Jacob, and Garnett Kelsoe. 1993. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells. Journal of Experimental Medicine 178:1293-1307. PMID: 8376935
    3. Joshy Jacob, and David Baltimore. 1999. Modeling T-cell memory by genetic marking of memory T cells in vivo. Nature 399: 593-597. PMID: 10376601
    4. Sanjay Garg, Alp Oran, Shin Sasaki, Charles H. Maris, Judith A. Kapp and Joshy Jacob. 2003. Genetic tagging shows increased frequency and longevity of skin-derived antigen-bearing dendritic cells in vivo. Nature Immunology 9:907-912. PMID: 12910266
    5. Charles Maris, Joseph Miller, John Altman and Joshy Jacob. 2003. A transgenic mouse model genetically tags all activated CD8 T cells. Journal of Immunology 171:2393-2401. PMID: 12928386
    6. Craig P Chappell and Joshy Jacob. 2006. Identification of memory B cells using a novel transgenic mouse model. Journal of Immunology 176: 4706-4715. PMID: 16585564
    7. Jin Kim, Ioanna Skountzou, Compans R, Joshy Jacob. 2009. Original antigenic sin responses to Influenza viruses. Journal of Immunology 183:3294-3301. PMID: 19648276
    8. Chelsey L. Goins, Craig P. Chappell, Rangaiah Shashidharamurthy, Periasamy Selvaraj and Joshy Jacob. 2010. Immune complex mediated enhancement of secondary antibody responses. Journal of Immunology 184: 6293-629. PMID: 20439912
    9. Ioanna Skountzou, Dimitrios G Koutsonanos, Jin Hyang Kim, Ryan Powers, Lakshmipriyadarshini Satyabhama, Feda Masseoud, William C. Weldon, Maria del Pilar Martin, Robert S Mittler, Richard Compans and Joshy Jacob. 2010. Immunity to pre-1950 H1N1 influenza viruses confers cross protection against swine-origin 2010 A (H1N1) influenza virus. Journal of Immunology 185: 1642-1649. PMID: 20585035;
    10. Sudhir Kasturi, Ioanna Skountzou, Randy Alberecht, Dimitrios Koutsonanos, Tang Hua, Helder Nakaya, Rajesh Ravindran, Shelley Stewart, Munir Alam, Niren Murthy, John Steel, Joshy Jacob, Robert Hogan, Adolfo Garcia Sastre, Richard Compans and Bali Pulendran. 2010. Programming the magnitude and persistence of antibody responses with innate immunity. Nature 470, 543–547. PMID: 21350488; PMC3057367
    11. Koutsonanos D.G., Martin M. del Pilar, Zarnitsyn V.G., Joshy Jacob, Prausnitz M.R., Compans R.W. and Skountzou I. 2011. Serological memory and long-term protection to novel H1N1 influenza virus after skin vaccination. Journal of Infectious Diseases 204: 582-591. PMID: 21685355; PMC3144165
    12. Jin Kim, Davis, WG, Suryaprakash Sambharra and Joshy Jacob. 2012. Strategies to alleviate original antigenic sin responses to influenza viruses. Proceedings of the National Academy of Sciences 109: 13751-13756. PMID: 22869731; PMC3427092
    13. Modesta Njau, Jin Kim, Craig Chappell, Rajesh Ravindran, Leela Thomas, Bali Pulendran and Joshy Jacob. 2012. CD28-B7 interaction modulates short- and long-lived plasma cell function. Journal of Immunology 89:2758-2767. PMID: 22908331
    14. Modesta Njau and Joshy Jacob. 2014. Inducible nitric oxide synthase is critical for plasma cell survival. Nature Immunology (in press)
    15. Abdul Khan, Aryn Price, Jillian Whidby, Matthew Miller, Alicja Cygan, Samantha Yost, Hannah Scarborough, Caitlin Bohannon, Joshy Jacob, Arash Grakoui, and Joseph Marcotrigiano. 2014. Structure of the Hepatitis C virus envelope glycoprotein-2. Nature (in press)
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