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Marcello DiStasio, MD, PhD

Instructor in Pathology

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Marcello DiStasio, MD, PhD

Research Summary

What role does inflammation play in the development and progression of degenerative diseases of the brain (such as Alzheimer’s disease) and retina (such as macular degeneration)? Activation of the innate immune system of the brain has been recently recognized as a significant component of numerous forms of neurodegenerative disease. My research aims to characterize the common pathways by which microglia, the primary phagocytic cells (consumers of debris) of central nervous system tissues, including the retina, switch from homeostatic (maintenance) to proinflammatory functions as part of disease progression. Using novel methods for single-cell RNA sequencing analysis (which characterizes the functional states of numerous cells at once) and multiplexed sequencing and proteomics in place on tissue (which allows us to visualize the location in tissues of many molecules, including RNA and protein), this work will identify immune system signaling pathways that are dysfunctional in degenerative disease. We hypothesize that there is a convergence of immune signaling pathways, meaning that the cells responsible for disruption of the normal processes that prevent damage to neurons become dysfunctional in stereotypical ways. This offers an opportunity for targeting these pathways using existing anti-inflammatory therapies. Thus, the goal is to characterize these pathways directly using human tissue samples and find key regulators of the transition from maintenance to inflammatory functions.

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