Kinchen, Jason M.
Primary Appointment
Assistant Professor of Research of Research, Microbiology, Immunology, and Cancer Biology
Education
- PhD, State University of New York at Stony Brook
Contact Information
Email: kinchen@virginia.edu
Research Interests
Signaling during apoptotic cell phagocytosis and degradation.
Research Description
Engulfment of apoptotic cells occurs throughout life in multi-cellular animals as part of normal development, homeostasis, and wound healing. The engulfment process can be broadly broken down into multiple steps comprising recognition of the dying cell by the phagocyte, which leads to internalization of the apoptotic cell corpse via Rac-dependent rearrangement of the actin cytoskeleton. Subsequently, the internalized apoptotic cell “matures” into an acidic phagolysosome structure leading to its eventual degradation and disposal, by a process termed ‘phagosome maturation.' In mammals, impaired clearance of apoptotic cells (at the level of recognition/internalization and degradation) results in onset of autoimmune diseases, such as systemic lupus erythematosus and chronic polyarthritis, potentially due to exposure of auto-antigens or a proposed role in the establishment of tolerance. One fundamental challenge in understanding how defects in corpse removal translate into diseased states is the identification of critical players that orchestrate the various steps of engulfment.
The focus of my research is the identification and characterization of signaling processes during apoptotic cell removal in nematode and mammalian models. ![](http://healthsystem.virginia.edu/internet/researchfaculty/images/kinchenphoto.jpg")
To identify novel players in this process, we use the nematode C. elegans, which represents a powerful genetic tool for the study of programmed cell death. Using this model, we have identified a novel pathway for the maturation of apoptotic cell-containing phagosomes. Subsequently, using biochemical and cell biological studies in mammalian cells, we have confirmed the relevance of this pathway in mammalian apoptotic cell removal and identified a novel mechanism for Rab5 recruitment to the phagosome involving the large GTPase dynamin. Our current research focuses on the identification of mechanisms by which Rab GTPases are functionally regulated (as well as recruited/retained on the phagosome) during apoptotic cell removal.