Shannon Kelley

Program: Immunology

Current advisor: Kodi S. Ravichandran, PhD

Undergraduate university: Towson University

Enrollment year: 2021

Research summary
Efferocytosis is the process by which professional and non-professional phagocytes remove apoptotic cells from the body. My research is focused on how “don’t-eat-me” signals fine-tune this process for healthy eating.

Billions of apoptotic cells are cleared from the body daily by professional and non-professional phagocytes – a process termed ‘efferocytosis’. Efferocytosis is an immunologically silent process, and impaired efferocytosis can elicit inflammatory pathologies and disrupt proper wound healing. An active area of research in phagocyte biology is to better understand how phagocytes efficiently clear apoptotic cells while maintaining cellular and tissue homeostasis. The balance of ‘eat-me’ and ‘don’t-eat-me’ signals communicated between target and phagocyte govern other forms of phagocytosis involving antibodies and complement proteins. Are don’t-eat-me signals involved in efferocytosis? If so, do these inhibitory signals influence which phagocyte populations eat, and how much they eat?
Don’t-eat‐me signals are delivered through phagocyte receptors bearing immunoreceptor tyrosine‐based inhibitory motifs (ITIMs). When activated by tyrosine phosphorylation, ITIMs bind tyrosine phosphatases such as SHP-1 (Ptpn6) and SHP‐2 (Ptpn11), which are thought to dephosphorylate proteins necessary for phagocytosis. However, many aspects of this process are poorly understood, including the downstream substrates of these phosphatases. Interestingly, two receptors important for efferocytosis, Axl and MerTK, also have putative ITIM motifs, thus supporting a potential role for these phosphatases in regulating efferocytosis. Our preliminary data suggest that SHP-2 may act as a molecular ‘brake’ on efferocytosis, and inhibition of SHP‐2 potentially enhances skin wound healing.

Graduate publications