The Fidler Lab

Atherosclerotic Plaques Are Full of Macrophages and Smooth Muscle Cells
Macrophage Mutants can be Identified in Plaques

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The Fidler Lab opened in the summer of 2023 in the Cardiovascular Research Institute at UCSF located on the Mission Bay Campus. The Fidler lab is focused on understanding how immune cells, primarily macrophages, promote atherosclerosis and cardiovascular disease. Macrophages play a critical role in atherosclerosis by retaining lipids and modulating the inflammatory landscape in vessels. Our Research centers on elucidating mechanisms by which dysfunctional macrophages promote atherosclerosis. The laboratory utilizes models of cardiovascular disease in animals to better understand the relationship between risk factors identified in humans and cardiovascular outcomes. These studies center on investigating genetic risk factors, and include a spectrum of conditions termed clonal hematopoiesis. Clonal Hematopoiesis occurs when hematopoietic stem cells acquire somatic mutations that provide a growth advantage. Although these mutations are typically associated with hematological malignancy, very few of these patients acquire cancers. Instead, clonal hematopoiesis confers a strong increased risk of cardiovascular disease. The Fidler lab is interested in identifying the molecular mechanisms linking clonal hematopoiesis and inflammation to cardiovascular disease.



Ppm1d and Atherosclerosis The Fidler lab is interested in understanding the link between Ppm1d mutations and cardiovascular disease. This R00 funded project seeks to understand why human epidemiological data which indicate that patients with PPM1D clonal hematopoiesis have increased cardiovascular disease including atherosclerosis. PPM1D is an important regulator of DNA damage response. The impact of PPM1D mutations on atherosclerosis are not well understood. Mutations in PPM1D can lead to decreased P53 activation and changes in DNA damage response. Interesting Ppm1d mutations are enriched in patients following radiation therapy. Projects in the lab are focused on understanding if PPM1D mutations promote atherosclerosis and under which contexts this may occur. 

Immune Cell Cross-Talk in Atherosclerosis The Atherosclerotic niche is composed of a complex variety of immune and vascular cells. The complex communication between these cells plays an essential role in modulating plaque stability and rupture. The Fidler lab is interested in uncovering how immune cells communicate with smooth muscle cells, fibroblast, endothelial cells, and other vascular cells to module atherosclerosis.



Graduate Students interested in rotating in the lab or interested Postdoctoral Candidates can contact us at [email protected] The Fidler lab is associated with multiple UCSF graduate programs.