Research Interests

Our lab is interested in understanding the molecular and cellular mechanisms that underlie tissue homeostasis in health and in disease. We investigate the role of TAM receptors and their agonists Protein S and Gas6 in development and throughout adulthood. We combine biochemical, cell-biological and genetically engineered mouse model approaches.

Tyro3, Axl, and MerTK comprise the TAM family of receptor tyrosine kinases. Together with their ligands Gas6 and Protein S (PROS1) TAM signaling plays a key role in maintaining a healthy balance in various physiological systems, including the endothelial, nervous, immune and reproductive systems.

Several human diseases are associated with the dysregulation of TAM signaling and its components, including blood hypercoagulation, inflammation, cancer, autoimmune disease and blindness.

We focus on the role of PROS1 as a TAM ligand in various physiological settings, to understand how PROS1-mediated TAM signaling is critical to homeostatic regulation. Specific projects in the lab focus on the developing and adult nervous system, the vascular system, in vision and in cancers.

Developmental focus of interest:

Protein S mediated TAM signaling in development:

Using advanced transgenic mouse models, we have showed that PROS1 is important for the development of blood vessels and for their healthy function in adulthood (Burstyn-Cohen et al, (2009) JCI). We are interested to learn more about the role of TAM signaling in the developing vasculature and the developing nervous system.

Protein S mediated TAM signaling in adult homeostasis:

In the eye: Mutations in MerTK lead to degeneration of photoreceptors, and consequent blindness in mice, rats and humans. However, the basic mechanism by which TAM signaling functions is not yet clear: what are the relevant ligand-receptor interactions? Which cells express them? In the lab, we aim to answer these questions in the eye, and to establish how PROS1 and TAM signaling is important for a healthy retina.

In cancer: TAMs were identified as proto-oncogenes, and their overexpression and hyper-activation is documented in many human cancers. However, which signals activate TAMs in cancers is not clearly understood. We study the role of PROS1-mediated TAM activation in various cancers, including in melanoma and the aggressive oral and lung carcinomas.