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Eileen F. Grady, Ph.D.
Associate Professor of Surgery
Contact Information
Department of Surgery
513 Parnassus Avenue, Room S-1268
Campus Box 0660
San Francisco, CA 94143-0660
Tel: 415-502-7920 or 415-476-6978
Fax: 415-476-0936
E:
Education
- B.A. (Biology and Theology), Fordham University, 1970-1974
Postdoctoral Training
- Ph.D. (Experimental Pathology, Cellular Immunology), University of California, San Francisco School of Medicine, 1975-1982
Biography
Eileen F. Grady, Ph.D. is an Associate Professor in the Department of Surgery at the University of California, San Francisco. Her research laboratory is in the UCSF Center for the Neurobiology of Digestive Diseases. Her research focuses on neuropeptides (substance P and calcitonin gene related peptide) that are involved in intestinal inflammation using cells and mice in which proteins regulating responses to these peptides have been altered by genetic or pharmacological approaches. She examines responses to these peptides and inflammatory insults (C. difficile Toxin A, the IBD model of IL10-/- mice treated with piroxicam) in the context of modified levels of (1) receptors such as the neurokinin 1 receptor, the calcitonin-like receptor and protease activated receptor 2; (2) channels such as transient receptor of the vanilloid type 1, 4, and A1; (3) enzymes such as neutral endopeptidase, endothelin-converting enzyme 1, tryptase, and trypsin 4; and (4) regulatory proteins, such as β-arrestin.
She is a recipient of the Thomas More Honors Program (1970-1972), the New York State Regents Fellowship and Incentive Award (1970-1974), the Graduate Division Regents Fellowship (1975-1978), the Patent Funds Grants for Thesis Work (1979-1981), Nominated for Excellence in Lab Instruction, Med I Teaching Awards (1997, 1998, 1999, 2000), and Nominated for A Major Contribution to Teaching by Med Student Class of 2003.
Dr. Grady is Principal Investigator of a Crohn's & Colitis Foundation of America grant (through 2010) and an NIH RO1 grant (through 2008). She is also a Co-Investigator on three additional, active NIH grants.
Her work on regulatory mechanisms by which G protein coupled receptors (GPCRs) in the gut mediate both short term and long term effects, as well as other areas of interest, has been extensively published in peer-reviewed journals.
Research Summary
The regulatory mechanisms by which G protein coupled receptors (GPCRs) in the gut mediate both short- and long-term effects. Short-term effects of neuropeptides include neurotransmission and neurogenic inflammation. I am mainly studying neurogenic inflammation, in which sensory nerves are stimulated to release pro-inflammatory peptides. Thus, I am studying neuropeptide or protease induced receptor activation (i.e., substance P and CGRP, or tryptase, trypsin), internalization and recycling of their G protein coupled receptors in cells and in intact animals.
I am particularly interested in the effects of degradative enzymes in the regulation of responsiveness to neuropeptides. I study this inflammation in the gut and pancreas using rats and transgenic mice in which the appropriate receptors, peptides, and the enzymes that degrade these peptides have been deleted (i.e. neurokinin 1 receptor (NK-1R), proteinase activated receptor-2 (PAR2), substance P, neutral endopeptidase, dipeptidyl peptidase I). Long-term effects of neuropeptides include chronic inflammation and pain. The mechanisms of desensitization, resensitization and down regulation must be examined to understand how some cells rapidly recover responsiveness even in the continued presence of ligand. Here the half life of a receptor, the selection process that regulates lysosomal sorting of a recycling receptor, and the number of times a particular receptor can signal to fresh ligand are key. I hope to understand in the intact animal: a) how regulation of responsiveness of GPCRs alters inflammation in the pancreas and gut; and b) how despite agonist induced desensitization, organs can maintain responsiveness to fresh ligand, leading to a continuous effect, such as gut motility.
Selected Publications
- Leopardi E., Rosenau W. Production of alpha-lymphotoxin by human T-cell subsets. Cellular Immunology 83;73-82, 1984.
- Leopardi E., Friend D., Rosenau W. Target cell lysis: Ultrastructural and cytoskeletal alterations. Journal of Immunology 133:3429-36, 1984.
- Grady E.F., Schwab M., Rosenau W. Expression of N-myc and c-src during the development of fetal human brain. Cancer Research 47:2931-36, 1987.
- Garland, A.M, Grady, E.F., Payan, D.G., Vigna, S.R., Bunnett, N.W. Agonist-induced internalization of the substance P (NK1) receptor expressed in epithelial cells. Biochemical Journal 303, 177-186, 1994.
- Bowden. J.J., Garland, A.M., Baluk, P., Lefevre, P., Grady, E.F., Vigna, S.R., Bunnett, N.W., McDonald, D.M. Direct observation of substance P-induced internalization of neurokinin 1 NK1 receptors at sites of inflammation. Proceedings of the National Academy of Sciences 91, 8964-8968, 1994.
