Fredman Lab

Albany Medical College, Department of Molecular and Cellular Physiology

 

Our Research

Our overall mission is to identify cellular and molecular mechanisms underlying failed inflammation-resolution programs in atherosclerosis and aging. 

 

Persistent, non-resolving inflammation is the underpinning of several prevalent human diseases. Therefore, understanding cellular and molecular mechanisms that promote the resolution of inflammation (or inflammation-resolution) is an unmet clinical need.

 The resolution response is in part mediated by specialized pro-resolving mediators, that include resolvins. We recently found that Resolvin D1 (RvD1) protects against atherosclerosis and may be a new way to treat this disease.

Macrophages are key players in atherosclerosis and aging . They take cues from their local environment and so understanding how to reprogram macrophages to resolve and repair as opposed to promote inflammation is a major focus of the lab.

RvD1-stimulated macrophage (LifeAct-RFP, red) engulfing a necroptotic cell (PKH67, green).

RvD1-stimulated macrophage (LifeAct-RFP, red) engulfing a necroptotic cell (PKH67, green).

The swift clearance of dead cells by macrophages (i.e. efferocytosis) is crucial for inflammation-resolution and tissue repair. Efferocytosis also limits inflammation and necrosis in tissues, therefore harnessing new therapies to promote this process is important for atherosclerosis and aging in general.

Optical slice of a macrophage (red) “nibbling” a necroptotic cell (green)

Optical slice of a macrophage (red) “nibbling” a necroptotic cell (green)

We identified that macrophages carry out a process called trogocytosis, which means to “gnaw” or “nibble”. The above image highlights an “arm-like” structure (in red) that reaches out to the necroptotic cell (green) to nibble small pieces. macrophage trogocytosis is an inefficient process and may be maladaptive in long-term diseases, like atherosclerosis.