John N. Forrest, Jr., M.D.
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Visting Faculty, Yale University School of Medicine
Membrane Biology
M.D., University of Pennsylvania, 1964
B.S., Ursinus College, Biology, 1960
Professor of Medicine
Director of Student Research
Yale University School of Medicine
The rectal gland of the primitive dogfish shark is an ideal model system, for it contains a high density of the receptors and channels that regulate chloride secretion in higher vertebrates, including humans. Our laboratory has used both physiological and molecular biological approaches to investigate peptides, G-protein coupled receptors, and channels involved in chloride transport in this tissue. We cloned the first gene identified in the shark and found that this gene encodes for a new class of heart natriuretic peptides (CNP) not previously found in cardiac tissue. We have also recently cloned from the rectal gland:
1. the membrane receptor for CNP
2. a unique adenosine receptor that regulates chloride secretion
3. the full length gene for shark CFTR, the gene that is defective in cystic fibrosis.
Using integrated methods that include perfusion studies, electrophysiological measurements, PCR, oocyte expression studies, and immunohistochemistry, our goal is to understand the interaction of these proteins in tissues of higher species, including the mammalian kidney and lung. We are also studying the effects of environmental toxins on signal transduction in the rectal gland and the role of tyrosine phosphorylation in the regulation of CFTR.
Environmental toxicants and disruption of signal transduction
Dr. Forrest’s laboratory is studying the effects of environmental toxicants on signal transduction in the shark rectal gland and the role of tyrosine phosphorylation in the regulation of CFTR. The rectal gland of the primitive dogfish shark is an ideal model system, for it contains a high density of the receptors and channels that regulate chloride secretion in higher vertebrates, including humans. The Forrest laboratory has used both physiological and molecular biological approaches to investigate peptides, G-protein coupled receptors and channels involved in chloride transport in this tissue, and the effects of toxicants on this process. Techniques include: preparation of RNA, DNA, PCR, gene cloning and sequencing, receptor binding studies, perfusion of the isolated shark rectal gland, cell culture, oocyte expression studies, immunohistochemistry, Western blots, and confocal microscopy.