Ford, Ian

Mentor: Dr. Steven Bensinger

Research project:

Cholesterol is the most abundant and well-known of a class of fatty acids known as sterols and is an essential molecule for mammalian life. Cholesterol can act as a cellular signaling modulator and is a precursor for bile acid and steroid synthesis. The abundance of cellular cholesterol is tightly regulated by a variety of genetic programs to ensure the proper fluidity of the plasma membrane and the dynamic movements of protein complexes. Recent studies have identified links between sterol metabolism and various aspects of innate and adaptive immune responses, ranging from cell-cycle progression to chemotaxis to effector cell function. The molecular mechanisms by which perturbations to sterol metabolism can affect immune function have only begun to be characterized in a systematic fashion in recent years, however.

Type I Interferons are essential immune signaling molecules which promote antigen presentation and pro-inflammatory signaling in innate cells in response to tumors or viral infection. Our lab has previously shown that perturbing cholesterol biosynthesis in macrophages results in spontaneous type I IFN signaling dependent on the protein STING (STimulator of INterferon Genes). My research is focused on identifying the mechanism by which cholesterol regulates STING-dependent IFN signaling. I will use a number of tools to investigate regulation of STING by cholesterol, including but not limited to a photo-crosslinkable cholesterol-mimetic probe for chemoproteomic methods and confocal microscopy to assess activity-dependent translocation. These findings will allow us to begin to unravel the tangled web of links between sterol metabolism and immune activity, and potentially allow for the development of new therapies for IFN-linked autoimmune disorders and enhancement of current anti-tumor immunotherapy approaches.