Research Associate Professor
Office: 90 Washington Street, Room 334B, Providence
Telephone: (401) 227-5309
- University of Massachusetts Medical School, Worcester, MA USA
PhD in Biomedical Sciences (Immunology)
- Christian Medical College, Vellore, India
Master of Science (M.Sc.) in Medical Microbiology
- Women’s Christian College, Madras, India
Bachelor of Science (B.Sc.) in Nutrition and Dietetics
Dengue viruses are mosquito-borne viruses that infect individuals in tropical and subtropical countries. They comprise four closely related but distinct viruses termed serotypes 1 through 4. Studies in humans infected with dengue provide strong evidence for an immunologic basis for the pathogenesis of severe disease dengue hemorrhagic fever (DHF).
Interactions between multiple components of the immune system during DENV infection. The primary targets of DENV replication are monocytes, macrophages and dendritic cells but B cells may also be infected with DENV. Antibodies secreted by B cells can mediate a wide range of functions including neutralization, ADE, ADCC and CDL. Virus-infected target cells secrete cytokines and chemokines and attract T cells. Viral peptides are presented on MHC Class I and Class II presentation pathways to CD8+ and CD4+ T cells respectively. CD4+ T cells predominantly produce cytokines but are capable of lysing virus-infected cells and CD8+ T cells lyse virus-infected cells and produce cytokines. The role of γδ T cells, Th17 and NK cell participation in the antiviral immune defense mechanisms requires further investigation. Question marks in the figure indicate that the evidence is not clear. The result of the cascade of immune activation leads to endothelial cell permeability and plasma leakage.
My research interests lie in assessing immune responses to acute viral infections with a focus on Natural Killer Cells and B lymphocytes.
UNDERSTANDING THE ROLE OF NATURAL KILLER CELLS IN REGULATING IMMUNE RESPONSES TO DENGUE.
Natural Killer cells are the primary effector cells of the innate immune response. NK cells are able to lyse virally infected cells and secrete large amounts of proinflammatory cytokines/chemokines without prior antigen sensitization. My laboratory recently found an interaction between a dengue peptide on the NS1 protein with KIR3DL1, a known inhibitory receptor on NK cells. We are interested in determining how dengue peptides modulate the function of subsets of NK cells. Furthermore we are interested in understanding whether NK cells are activated and contribute to protection or pathogenesis of severe dengue disease. Using clinical samples from a long standing cohort in Thailand we would like to evaluate NK cell activation using multi-parametric flow cytometry.
UNDERSTANDING THE ROLE OF ANTIGEN-SPECIFIC B CELLS IN PROTECTION FROM OR INCREASING THE RISK OF SEVERE DENGUE DISEASE.
Antibodies generated in humans to DENV are of particular clinical relevance, because they have the potential during a subsequent infection to protect from or increase the risk of developing several dengue disease. Although much is known regarding the specificity and efficacy of antibody responses, our knowledge of the function, phenotype, and specificity of the antigen-specific B cells that are responsible for antibody production, as well as for long-term humoral memory, is inadequate. We have recently developed reagents that enable the tracking of antigen-specific memory B cells. Using clinical samples we would like to create an immunoprofile of activated and memory B cells that may provide prognostic markers for dengue immunity and/or immunopathology.
- Elizabeth Townsley, Geraldine O’Connor, Cormac Cosgrove, Marcia Woda, Mary Co, Stephen J. Thomas, Siripen Kalayanarooj, Robert V. Gibbons, Ananda Nisalak, Anon Srikiatkhachorn, Sharone Green, Henry A.F. Stephens, Daniel McVicar, Galit Alter, Alan L. Rothman, Mathew A. Interaction of a dengue-specific CD8+ T cell NS1 epitope with KIR3DL1 on NK cells reveals an underappreciated role for NK cells in impacting dengue disease severity. Clin.Exp.Immunology. 2015 Oct 6. doi: 10.1111/cei.12722. PMID 26439909.
- RothmanAL, Currier JR, Friberg HL, Mathew A. Analysis of cell-mediated immune responses in support of dengue vaccine development efforts. Vaccine. 2015 Oct 14. pii: S0264-410X(15)01394-8. doi: 10.1016.
- Marcia Woda and Mathew A. Use of fluorescently labeled dengue viruses as probes to identify antigen specific memory B cells. J.Immunol.Methods. 2015. 416: 167-177. PMID 25497702
- Smita Jaiswal, Marcia Woda, Pamela Pazoles, Leonard D. Shultz, Dale L. Greiner, Michael Brehm and Mathew A. Dengue virus infection induces broadly cross-reactive antibodies that recognize intact virions in humanized BLT-NSG mice. Exp.Biol & Med. 2015 Jan; 240(1):67-78. PMID 25125497.
- Mathew A, Elizabeth Townsley and Francis A Ennis. Elucidating the Role of T cells in Protection Against and Pathogenesis of Dengue Virus Infections. Future Microbiology. Review Article. 2014 9(3) 411-425. PMID 24762312.
- Elizabeth Townsley, Marcia Woda, Stephen J. Thomas, Siripen Kalayanarooj, Robert V. Gibbons, Ananda Nisalak, Anon Srikiatkhachorn, Sharone Green, Henry A.F. Stephens, Alan L. Rothman, Mathew A. Distinct Activation Phenotype of a Highly Conserved Novel HLA-B57-Restricted Epitope during Dengue Virus Infection. Immunology. 2014. Jan. 141(1):27-38. PMCID: PMC3893847.
- Joel M. O’Bryan, Marcia Woda, Mary Co, Mathew A, Alan L. Rothman. Telomere length dynamics in human memory T cells specific for viruses causing acute or latent infections. Immunity and Ageing. 2013. 10:37 PMCID: PMC3765437.
- Alejandro Ramirez, Vijay Rathinam, Katherine A Fitzgerald, Douglas T Golenbock and Mathew A. Defective pro-IL-1b responses in macrophages from aged mice. Immunity and Ageing. 2012. Dec 11;9(1):27.PMCID:PMC3545921.
- Friberg H, Jaiswal S, West K, O’Ketch M, Rothman A.L., Mathew A. Analysis of human monoclonal antibodies generated by dengue virus-specific memory B cells. Viral Immunology. 2012. Oct 25(5):348-59. PMCID: PMC3466914.
- Jaiswal S, Pazoles P, Woda M, Shultz LD, Greiner DL, Brehm MA, Mathew A. Enhanced humoral and HLA-A2-restricted dengue virus-specific T cell responses in humanized BLT NSG mice. Immunology. 2012. Jul. 136(3):334-43. PMCID: PMC3385033.
- Mathew A, West K, Kalayanarooj S, Gibbons RV, Srikiatkhachorn A, Green S, Libraty D, Jaiswal S, Rothman AL. B cell Responses During Primary and Secondary Dengue Virus Infections in Humans. J.Infect.Dis. 2011. Nov 15;204(10):1514-22 PMCID: PMC3222107.
- Friberg H, Bashyam H, Toyosaki-Maeda T, Potts JA, Greenough T, Kalayanarooj S,. Gibbons RV, Nisalak A, Srikiatkhachorn A, Green S, Stephens HAF, Rothman AL, Mathew A. Cross-Reactivity and Expansion of Dengue-Specific T cells During Acute Primary and Secondary Infections in Humans. Nature:Scientific Reports. 2011. Aug. SREP-11-00174.3d 26/7/11 14:31:38. PMCID: PMC3216538.
- Green S, Ennis FA, Mathew A. Long term recall of memory CD8 T cells in mice to first and third generation smallpox vaccines. Vaccine. 2011. Feb 11. 29(8):1666-76. PMCID: PMC3069729.
- Coreen M Beaumier, Smita Jaiswal, Kim Y West, Heather Friberg, Mathew A, Alan L Rothman. Differential in vivo clearance and response to secondary heterologous infections by H2b– restricted dengue virus-specific CD8+ T cells. Viral Immunology. 2010. 23(5): 477-485. PMCID: PMC2967818.
- Heather L. Friberg, Lynne Burns, Marcia Woda, Siripen Kalayanarooj, Timothy P. Endy, Henry A.F. Stephens, Sharone Green, Alan L. Rothman, Mathew A. Altered human T cell functional responses to heterologous dengue epitope variants correlate with TCR triggering of ERK phosphorylation. Immunology and Cell Biology. Apr 27.PMCID: PMC2929403.
- Smita Jaiswal, Todd Pearson, Heather Friberg, Leonard Shultz, Dale Greiner, Alan L. Rothman, Mathew A. Adaptive dengue virus-specific immune responses in humanized NOD-scid IL-2rgnull PLoS ONE 2009. Oct 5. 4(10):e7251 PMCID: PMC2749937.
- Mathew A, Joel O’Bryan, William Marshall, Girish J. Kotwal, Masanori Terajima, Sharone, Green, Alan L. Rothman, Francis A. Ennis. Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L deleted vaccinia virus. PLoS ONE 2008. Oct 2;3(10):e3323. PMCID: PMC2553181.
- Mathew A, Alan L. Rothman. Understanding the contribution of cellular immunity to dengue disease pathogenesis. Immunological Reviews. Oct 225(1):300-13. PMID:18837790.
- Coreen Beaumier, Mathew A, Hema Bashyam, Alan L. Rothman. Cross-reactive Memory CD8+ T cells Cause an Enhanced Immune Response in Heterologous Secondary Dengue Virus Infections in Mice. J.Inf.Diseases. 2008. Feb 15;197(4):608-17. PMID: 18275279.
- Steven Hatch, Mathew A, Alan L. Rothman. Dengue Vaccine: Opportunities and Challenges. iDrugs 2008. Jan;11(1):42-5.
- Qian Yuan, Gabriele S Campanella, Richard A Colvin, Daniel L Hamilos, Krister J Jones, Mathew A, Terry K Means, Andrew D Luster. Membrane-bound eotaxin-3 mediates eosinophil transepithelial migration in IL-4-stimulated epithelial cells. J.Immunol. 2006.36(10)2700-2714.
- Mathew A, Masanori Terajima, Kim West, Sharone Green, Alan L. Rothman, Francis A. Ennis and Jeffrey S. Kennedy. Identification of murine poxvirus-specific CD8+ CTL epitopes with distinct functional profiles. J.Immunol. 2005.174:2212-2219.
- Mathew A, Benjamin D. Medoff, Andrew D. Carafone and Andrew D. Luster.Th2 Cell Trafficking to the Allergic Lung is Dependent on Chemoattractant Signaling. J.Immunol. 2002. Cutting Edge. 169:651-655.
- Benjamin D Medoff , Alain Sauty, Andrew M. Tager, James A. Maclean, R.N. Smith, Mathew A, Jennifer H. Dufour, Andrew D. Luster. IFN-gamma-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma. J.Immunol. 2002. 168(10):5278-86.
- Mathew A, James A. MacLean, Elliot DeHaan, Andrew M. Tager, Francis H.Y. Green, Andrew D. Luster. Signal Transducer and Activator of Transcription Factor 6 Controls Chemokine Production and T Helper Type 2 Cell Trafficking in Allergic Pulmonary Inflammation. J.Exp.Med. 2001. 193 (9): 1087-1096.
- Mathew A, Francis A. Ennis, Alan L. Rothman. Transient Decreases in Human T cell Proliferative Responses Following Vaccinia Immunization. Clin.Immunol. 2000. 96(2) 100-107.
- Mathew A, Ichiro Kurane, Sharone Green, David W. Vaughn, Siripen Kalyanarooj, Saroj Suntyakorn, Francis A. Ennis, Alan L. Rothman. Impaired T cell Proliferation in Acute Dengue Infection. J.Immunol. 1999. 162(9): 5609-15.
- Margo A. Brinton, Ichiro Kurane, Mathew A, Lingling Zeng, Pei Yong Shi, Alan Rothman, Francis A. Ennis. Immune Mediated and Inherited Defenses Against Flaviviruses. Clin.Diagn.Virol. 1998. 15:10(2-3) 129-139.
- Mathew A, Ichiro Kurane, Sharone Green, Henry A.F. Stephens, David W. Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Dasnayanee Chandanayingyong, Francis A. Ennis, Alan L. Rothman. Predominance of HLA Restricted CTL Responses to Serotype Crossreactive Epitopes on Nonstructural Proteins following Natural Secondary Dengue Virus Infection. J.Virol. 1998. 72(5):3999-4004.
- Mathew A, Ichiro Kurane, Alan L. Rothman, Ling Ling Zeng, Margo A. Brinton, Francis A. Ennis. Dominant Recognition by Human CD8+ Cytotoxic T lymphocytes of Dengue Virus Nonstructural Proteins NS3 and NS1.2a. J.Clin.Invest. 1996.98(7):1684-1692.