Thomas Jefferson UniversitySidney Kimmel Medical College

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Overview

The Laboratory for Signal Transduction Research focuses on basic, translational and clinical studies of the role of signaling molecules in health and disease. The laboratory comprises 6,000 sq ft subdivided into 6 individual modules housing ~20 investigators, with core facilities for equipment and computer support.

Research in this laboratory focuses specifically focuses on the regulation and role of guanylyl cyclases in (patho)physiology. Guanylyl cyclases are proteins important in transmembrane signaling mediating a variety of processes, including cardiovascular homeostasis, intestinal fluid and electrolyte balance, and visual phototransduction. One program examines the molecular regulation of guanylyl cyclase-receptor coupling and signaling through its catalytic domain. Thus, nucleotides allosterically regulate signaling through this mechanism as part of a general response to cellular insult and stress. In contrast, calcium allosterically inhibits guanylyl cyclases as part of a reciprocal mechanism coordinating the concentration of antagonistic intracellular second messengers calcium and cyclic GMP.

A second program examines the role of one member of the guanylyl cyclase family, guanylyl cyclase C in mediating enterotoxigenic diarrhea, a leading cause of endemic diarrhea in the world.

A third program examines the utility of guanylyl cyclase C for diagnosing and treating patients with upper and lower gastorintestinal malignancies. Indeed, some of these investigations involve clinical trials of the utility of this guanylyl cyclase to serve as a marker for staging patients with colorectal cancer and their post-operative surveillance.

A fourth program explores the utility of guanylyl cyclase C as a vaccine target for metastatic colorectal cancer.

Finally, the role of guanylyl cyclases in regulating the growth and proliferation of normal and neoplastic cells is actively being explored in this laboratory.