“Cell Therapy: An Emerging Drug Class” Biju Parekkadan, PhD Assistant Professor of Surgery Harvard Medical...
Catherine Valentine M.D.
Assistant Professor of Medicine and Pathology and Laboratory Medicine
ADDITIONAL DIVISION/DEPT TITLES
Medical School: New York University School of Medicine
Internship: NYU Medical Center/Bellevue Hospital
Residency: NYU Medical Center/Bellevue Hospital
Fellowship: National Institutes of Health
Other Post-doctoral Fellowships/Training: Infectious Disease-Massachusetts General Hospital
Board Certifications: (e.g. Internal Medicine, Pulmonary Medicine, Critical Care Medicine, Allergy, Sleep) Internal Medicine, Critical Care Medicine, Infectious Diseases
RESEARCH: Innate and adaptive immune responses during sepsis
CLINICAL: Management of infectious diseases in critically ill patients
My research interests focus on the host immune response to infection in the setting of gram-negative bacterial sepsis. This syndrome is characterized by a dysregulated immune response to infection consisting of an intense innate response followed by an ‘immunoparalytic’ state when most patient deaths occur. In order to manage the complex immunopathology that occurs in these patients, it is necessary to have a more fundamental understanding of the immune responses that occur during the course of infection. Toll-like receptors (TLRs) serve as a crucial link between the innate and adaptive arms of the immune response, and provide a mechanism by which microbial products are able to modulate both the innate and adaptive immune responses to gram-negative infection. The broad goals of my research program are: 1) to study Toll-like receptor mediated innate immune responses to gram negative bacteria, 2) to characterize costimulatory molecule expression on antigen presenting cells (APC) in response to stimulation with different bacterial TLR ligands, and how this process alters APC- T cell interactions and modulates the subsequent adaptive immune response, and 3) to determine how these TLR mediated mechanisms may regulate the complex hyper-inflammatory and immunosuppressive states observed during gram-negative bacterial sepsis.
Concurrent stimulation of different TLRs can result in synergistic or antagonistic induction of inflammatory cytokines. Similar signaling pathways may also regulate the cellular response during infection. My current research is focused on TLR induced expression of costimulatory molecules on antigen presenting cells (APCs). These molecules function as part of the immunological synapse and can determine if a positive or negative signal for T-cell activation is presented by the APC. We have found that TLR induced expression of CD80, CD86 and PD-L1 by macrophages in vitro can be modulated by simultaneous activation of another TLR signaling pathway. Therefore the T-cell response during infection may be determined by the costimulatory molecules expressed by APCs in response to the specific TLR ligands present. Further studies of APC costimulatory molecule expression and T cell responses in vivo, using highly purified TLR ligands and infection models in wildtype and knockout mice lacking specific TLRs will give further insight into how TLR mediated activity directs the cellular response to infection. In addition, in vitro studies will establish the molecular mechanisms of ‘cross-talk’ between different TLR signaling pathways to determine how individual ligands influence each other’s activity and alter the immune response during infection.
1. Aranya Bagchi, Elizabeth A. Herrup, H. Shaw Warren, James Trigilio, Hae-Sook Shin, Catherine Valentine and Judith Hellman. MyD88 Dependent and Independent pathways in synergy, priming and tolerance between Toll-Like Receptor agonists. Journal of Immunology. 2007;178(2):1164-1171
2. Catherine H. Valentine, Judith Hellman, Laura K. Beasley-Topliffe, Aranya Bagchi and H. Shaw Warren. Passive immunization to outer membrane proteins MLP and PAL does not protect mice from sepsis. Molecular Medicine. 2006;12(9-10):252-258