| Bruce S. Babiarz, Ph.D., Professor C214 Nelson Labs 604 Allison Road Piscataway, NJ 08854-6999 VOICE: (732) 445-2805 FAX: (732) 445-1794 babiarz@biology.rutgers.edu Visit the Babiarz Lab |
Research Summary
Mammalian development
My laboratory is interested in the process of embryo implantation, using the mouse as a model system. Implantation involves the invasion by embryo derived trophoblast giant cells into the decidualized uterine stroma. Decidua is thought to provide a barrier to unchecked trophoblast invasion, but is a transient tissue. Between days 8-10 of development, decidua undergoes programmed cell death to create space for the growing embryo. Our work is directed towards understanding the interaction between the trophoblast and decidua during this process. Current work has focused on identifying the signals and cellular changes which underlie decidual regression and the resulting trophoblast phagocytosis of the cellular debris.
RESEARCH SUMMARY
The current work in my laboratory focuses on the expression of the cathepsin proteinases (B and L) and their physiological inhibitors, the cystatins both in vivo and in vitro. We have found that both cathepsin B (CB) and cathepsin L (CL) are upregulated during differentiation of trophoblast giant cells in vivo. CB and CL are also expressed by the decidualizing stroma in areas associated with matrix remodeling and both CB message and protein are upregulated durng the apoptotic regression of the decidua in vivo. Work is currently in progress using in vitrosystems to study the control of the these enzymes and inhibitors. Using outgrowths of trophoblast giant cells from ectoplacental cone rudiments, we confirmed the upregulation of CB and CL during giant cell differentiation, associated with both the lysosomal compartment and as secreted pro-forms. The regulation of these enzymes in the rat trophoblast cell line (Rcho-1) and human trophoblast tumor cell line (JAR) is presently underway.
In vitro cultures of decidualizing stroma show similar upregulation of the cathepsins and cystatin C as observed in vivo. Relative to the control of this system, the effects of extracellular matrix and soluble signaling molecules (e.g. EGF, TGF-, FGF) on enzyme and/or inhibitor synthesis is being investigated. Preliminary results suggest that both EGF and TGF- induce cystatin C synthesis in decidual cultures, with FGF and fibronectin showing inhibitory effects.