Laboratory for Signal Transduction Research

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 six 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 gastrointestinal 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.

This facility is equipped to support the full spectrum of laboratory-based investigations employing the techniques of biochemistry, molecular biology, genetics, physiology, pharmacology, computational and structural biology, pathology, genomics, proteomics, analytical chemistry, and translational medicine.

This Laboratory for Signal Transduction is comprised of six modern modules of ~600 sq. ft., each equipped with fume hoods and attached offices. In addition, there are two 150-sq.-ft. cell culture facilities, a microscopy suite, a darkroom, a walk-in cold (4oC) room, offices, a meeting room, and centralized computer facilities.

Equipment Includes:

• An ABI 7900HT Sequence Detection System, ultra-, low-speed, and benchtop refrigerated centrifuges;
• Savant evaporator with pump;
• Gel dryers;
• Laminar flow, bacteriology, and molecular biology hoods;
• CO2 incubators;
• Gamma and liquid scintillation counters;
• Spectrophotometer;
• Polyacrylamide and sequencing gel electrophoresis components with high voltage power supplies;
• -20°C freezers and refrigerators;
• -70°C freezers;
• pH meters, balances, homogenizers, sonicators, tissue disruptors;
• Blotting apparatuses;
• HPLC systems with UV and electrochemical detectors;
• Automated 96-well plate reader;
• Automated densitometer for scanning slab gels;
• Automated thermocyclers for PCR analyses.

In addition, there is access to the full complement of core services and equipment offered by the Institute for Translational Medicine in the Department of Medicine and the Kimmel Cancer Center.

Studies in this facility currently focus on:

• Detection and treatment of gastrointestinal malignancies.
• Molecular mechanisms underlying neoplastic transformation.
• Novel clinical marker and target discovery.
• Molecular mechanisms underlying enterotoxigenic diarrhea.
• Key signaling mechanisms in cardiovascular (patho)physiology.
• Translational clinical trials exploring the utility of molecular diagnostics in managing patients with malignancies.