THE UPSTATE DISCOVERY CHALLENGE
STRATEGIC PLAN FOR RESEARCH IN IMMUNITY AND AUTOIMMUNITY IN DISEASE (IMMUNE- MEDIATED DISEASE) Introduction: The main goal of our working group was to envision research directions over the next several years in the area of immune-mediated diseases. As these diseases often occur in a tissue-specific manner and involve multiple different immune mechanisms, research projects are highly collaborative and require significant integration across multiple scientific disciplines. After consultation with interested faculty at Upstate, our working group expressed a strong commitment to defining pathways to propel research in immune-mediated disease at Upstate. Our working group agreed that the focus on immune-mediated diseases is represented by Upstate faculty in three main areas. These are diseases associated with 1) autoimmunity to self-antigens by adaptive arms of the immune system, 2) sterile immunopathology mediated by innate responses, and 3) pathogen-induced immunopathology by both innate and adaptive immunity. All three of these areas are well-represented in current Upstate research programs and constitute a significant strength for further development. In particular, diseases of interest in the first group (autoimmunity) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type I diabetes, and inflammatory diseases associated with transplant immunology. These immune-mediated diseases are driven by autoimmune reactions to self or allogeneic antigens by cells of adaptive immunity gone awry, including T and B cells. Of particular note, research in autoimmunity at Upstate has led to the development of the Lupus, Autoimmunity, Inflammation and Immune Health Center of Excellence (LACE) as described later. Basic scientists, primarily but not exclusively in the Department of Microbiology and Immunology, have significant national prominence in T and B cell biology that could be further integrated with both clinical and basic science faculty in development of multi-disciplinary research on these immune-mediated diseases. In the second area (sterile innate immunopathology) we have faculty working on pathogenic immune responses associated with oxidative and proteostatic stress, inflammasome activation by abnormal extracellular crystals, ischemia-reperfusion reactions in the CNS and heart muscle, and mechanical injury of the lungs as a result of ventilation. Lastly, the area of pathogen-induced immunopathology has been recently appreciated as the cause of multiple tissue-specific diseases including neurodegenerative diseases. These diseases commonly are caused by either persistent infections as in the case of hepatitis C virus or latent virus infections that periodically reactivate to promote chronic tissue inflammation as in multiple human herpesvirus infections. More recently, acute and chronic proinflammatory activities are believed to cause debilitating neurocognitive dysfunctions in Covid-19 survivors. Mechanistic studies of these diseases are focused on both tissue-specific tropism of the virus and consequent inflammation that cause abnormalities in tissue function. Molecular understanding of signaling molecules induced by microbial materials including proinflammatory cytokines in acute and chronic inflammatory disease have been a recent and fruitful area of research into the cause and cure of these diseases. The later would include research being performed at Upstate in the Sepsis Interdisciplinary Research
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