Justin S. A. Perry, Ph.D. M.A.
Cancer Research Institute - Mark Foundation Postdoctoral Fellow
Studying the mechanisms of apoptotic cell clearance during homeostasis and cancer development/progression
For an organism to maintain homeostasis, millions of cells must undergo apoptosis and be cleared daily in a way that is rapid, efficient, and immunologically quiescent. To achieve this, a single phagocyte will often undertake clearance of multiple dead cells in rapid succession. The consequences of this level of eating to a phagocyte are extensive. First, the phagocyte must generate energy to continually find, engulf, and digest each subsequent corpse. Second, the phagocyte must cope with the sudden influx of biological material inherited from engulfed apoptotic cells. Our current knowledge of how a phagocyte manages engulfment and digestion of apoptotic corpses remains sparse. Understanding the mechanisms by which a phagocyte engulfs and digests corpses is particularly important, because immune evasion by a tumor relies on phagocytosis of tumor cells to establish a tolerogenic microenvironment. The importance of this process is underlined by the growing interest in cancer immunotherapies targeting immune tolerance established by phagocytes (e.g., anti-CD47). Unfortunately, current immune therapies rely on expression of specific surface proteins which are often heterogeneously expressed within and across cancer types. Ideally, an immunotherapy should both boost clearance of the tumor cell and promote an inflammatory anti-tumor response, without relying on heterogeneously expressed proteins. To develop optimal immunotherapeutics, more in depth understanding of both how phagocytes internalize and digest apoptotic corpses, and how phagocytes establish immune tolerance, are needed.
Consequently, Dr. Perry is investigating mechanisms of cancer cell clearance hoping to co-opt knowledge obtained to develop means to enhance immune responses against cancer and ultimately improve the effectiveness of immunotherapy for cancer patients.
This research is generously funded by the Cancer Research Institute, the Mark Foundation, the Burroughs Wellcome Trust, and the National Cancer Institute/National Institutes of Health.