Dr. Ayala's research focuses on several areas; (1) the differential effects of sepsis on immune cell function, (2) the role of programmed cell death/apoptosis in immune dysfunction observed following hemorrhage and/or sepsis, and (3) the contribution immune and/or non-immune cell expression of co-inhibitory cell surface molecules/”check-point” protein expression contributes to the development of acute lung injury resultant from shock and/or septic insults.
Recently, the work in Dr. Ayala’s lab has centered on developing a better understanding of what the patho-physiological mechanisms of shock, tissue injury and/or sepsis have on the individual that lead to increasing their susceptibility to subsequent multiple organ failure. Importantly, the lab has tried to do this through not only the application of what they believe are valuable pre-clinical animal models, but also through collaborative partnerships with clinician scientists here at Rhode Island Hospital and around the world, which can translate the significance of bench-side observations back to the critically ill patient.
Biography
Dr. Ayala is Professor of Surgery (Research) and the Director of the Division of Surgical Research at Rhode Island Hospital/the Alpert School of Medicine at Brown University. He has been recognized by his peers through election as a “Fellow”-American Association for the Advancement of Science (AAAS) (22’). He was a NIH-NIGMS-Consultant/Panel member for ‘National Advisory General Medical Sciences (NAGMS) Working Group on Sepsis’ (18'-19'). He served as a standing member of the National Institutes of Health (NIH)-Lung Cellular Molecular & Immunology (LCMI)-Study Section as well as previously on the NIH-Surgery Anesthesia Trauma (SAT)-Study Section, and has served as an ad hoc on various NIH site visit teams/SEPs/ad hoc review panels, the Veteran's Administration (VA)-Department of Defense (DoD) Merit Review Board, Wellcome Trust as well as Shriners Research Hospitals (over 12 years). He has been recognized by his peers through election to President (04'-05'), Treasurer (02'-04'), and Scientific Program Chairman (01) of the Shock Society; as selection as Recorder/Executive Council (05'-07') of the Surgical Infection Society, and by appointment to the Society of Leukocyte Biology council (11'-13'). Dr. Ayala was also the recipient of a "Maximizing Investigators' Research Award (MIRA)" for Established Investigators (R35) from the NIH-NIGMS (16'); the Shock Society's 10th annual 'Scientific Achievement Award' (07'); and the 15th annual 'Distinguished Service Award' (09'). He has over 300 manuscripts/review articles to his credit and has been continuously funded by the NIH since 1991. He is also a member of the training faculty of the Brown University Graduate Pathobiology Program; the Therapeutic Sciences Graduate Program, the Department of Cell Biology, Molecular Biology & Biochemistry Graduate Program; and is an adjunct Professor/mentor in the Univ. R.I. graduate program in the Department of Cellular & Molecular Biology. During his tenure at Brown University and previously at Michigan State University he has had the privilege of mentoring students ranging from undergraduates and medical students to surgical residents, post-doctoral fellows and Junior Faculty. Research interests include projects looking at: the differential effects of sepsis on immune cell function; the role of programmed cell death/ apoptosis in immune dysfunction observed following hemorrhage and/or sepsis; as well as, the contribution of 'checkpoint' protein/ accessory molecule expression to the pathological process mediating acute lung injury resultant from shock and/or septic insults.
Research Overview
Research interests include projects looking at: 1) determining how select expression of cell surface co-inhibitory proteins (checkpoint proteins) and their ligands, on innate immune cells as well as non-immune cells; alter the morbid events associated with adult sepsis. 2) Utilizing a novel model of indirect-acute lung (iALI) to ask how checkpoint protein expression affects the patho-mechanisms driving iALI. Finally, 3) since the neonate possesses a unique/ naive immune system and is more susceptible to morbid response in the face of infectious challenge, we are examining if the expression of checkpoint protein family members have a comparative impact on the neonate's response to septic insult.
Research Statement
The work in our laboratory has centered on understanding the patho-physiological effects of shock/ tissue injury/ sepsis that lead to immune dysfunction and subsequent multiple organ failure in the critically ill trauma patient (through animal modeling and collaborative clinical studies). We have described, over the years, numerous deficits in both components of cell-mediated (T-cell, NKT-cell, gd T-cell, Treg-cell, ILC2, etc) and innate (macrophage, neutrophil, dendritic cells) immune responsiveness induced by shock or sepsis, which are underpinned by alterations in cell signaling, protein translation and transcription patterns. Particular emphasis has been directed at defining the role of soluble mediators (e.g., IL-4, IL-10, IL-16, IL-33, MCP-1, MIP-2/KC/IL-8, TGF-b, PGE2, NO, steroids, etc.), inhibitory receptors/checkpoint proteins (e.g., PD-1:PD-L1/L2, BTLA:HVEM, VISTA, FasL:Fas, etc.) and/or cellular pathways (e.g., p38 MAPKs, STATs, SOCS 1/3, Shp1/2, Rip1/3, NFkB, etc.) involved in orchestrating these changes in mouse models and critically ill patient. We have also found evidence of alterations of the immune cell's apoptotic process, present in these animals and are actively examining the contribution of this pathway. It is our hope that, by understanding the cellular/molecular mechanisms which control these alterations in the traumatized or septic animal/patient, we will improve our ability to treat them.
Major Theme of Research: injury, shock, organ dysfunction, immunology and infection