Michael K. Cooper, M.D.

Associate Professor

michael.cooper@vanderbilt.edu

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Faculty Appointments
Associate Professor of Neurology
Education
M.D., MEDICINE, University of Alabama, Birmingham, AlabamaB.S., Rhodes College, Memphis, Tennessee
Office Address
MRB III, Rm. 6140
465 21st Avenue South
Nashville, TN 8552
Research Description
In the laboratory we study molecular signaling pathways in the developing nervous system. We are interested in learning how inductive signals are generated, received and implemented to coordinate cellular growth and differentiation during brain and spinal cord development. Hedgehog proteins are one of several secreted signaling molecules that are essential for normal embryonic development. Sonic hedgehog is the best characterized of three vertebrate Hedgehog signaling proteins and is of considerable interest because of its role in directing the fate of neuronal progenitor cells and in the initiation and growth of medulloblastomas, a pediatric brain tumor. Past efforts have been directed at the identification and characterization of teratogenic, plant-derived compounds as modulators of the Hedgehog pathway. These studies have served to further our understanding of how the Hedgehog signal transduction apparatus functions, to provide tools for dissecting the roles of Hedgehog signaling in both neurogenesis and organ function, and to identify a potential mechanism-based cancer therapy. Current research efforts are directed at understanding the molecular events through which Hedgehog signaling influences progenitor cell proliferation and neuronal specification. To gain a molecular understanding of these cellular responses we have recently embarked on a systematic effort to identify and characterize Sonic hedgehog gene targets. In addition to learning more about how cells respond to Hedgehog signaling in the developing brain, we are using this information to explore later roles for Hedgehog signaling in neurogenesis within the adult brain. Our hope is that molecular insight into normal pathways of neurogenesis can contribute to the understanding of a host of nervous system diseases and to better strategies for the treatment of those disorders.
Research Keywords
Neural Development.
Publications
Ehtesham M, Sarangi A, Valadez JG, Chanthaphaychith S, Becher MW, Abel TW, Thompson RC, Cooper MK. Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells. Oncogene [print-electronic]. 2007 Aug 8/23/2007; 26(39): 5752-61. PMID: 17353902, PII: 1210359, DOI: 10.1038/sj.onc.1210359, ISSN: 0950-9232.

Cooper MK, Wassif CA, Krakowiak PA, Taipale J, Gong R, Kelley RI, Porter FD, Beachy PA. A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis. Nat. Genet [print-electronic]. 2003 Apr; 33(4): 508-13. PMID: 12652302, PII: ng1134, DOI: 10.1038/ng1134, ISSN: 1061-4036.

Chen JK, Taipale J, Cooper MK, Beachy PA. Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev. 2002 Nov 11/1/2002; 16(21): 2743-8. PMID: 12414725, PMCID: PMC187469, DOI: 10.1101/gad.1025302, ISSN: 0890-9369.

Berman DM, Karhadkar SS, Hallahan AR, Pritchard JI, Eberhart CG, Watkins DN, Chen JK, Cooper MK, Taipale J, Olson JM, Beachy PA. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science. 2002 Aug 8/30/2002; 297(5586): 1559-61. PMID: 12202832, PII: 297/5586/1559, DOI: 10.1126/science.1073733, ISSN: 1095-9203.

Taipale J, Cooper MK, Maiti T, Beachy PA. Patched acts catalytically to suppress the activity of Smoothened. Nature. 2002 Aug 8/22/2002; 418(6900): 892-7. PMID: 12192414, PII: nature00989, DOI: 10.1038/nature00989, ISSN: 0028-0836.

Muñoz-Sanjuán I, Cooper MK, Beachy PA, Fallon JF, Nathans J. Expression and regulation of chicken fibroblast growth factor homologous factor (FHF)-4 during craniofacial morphogenesis. Dev. Dyn. 2001 Mar; 220(3): 238-45. PMID: 11241832, PII: 10.1002/1097-0177(20010301)220:3<238::AID-DVDY1104>3.0.CO;2-T, DOI: 10.1002/1097-0177(20010301)220:3<238::AID-DVDY1104>3.0.CO;2-T, ISSN: 1058-8388.

Taipale J, Chen JK, Cooper MK, Wang B, Mann RK, Milenkovic L, Scott MP, Beachy PA. Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine. Nature. 2000 Aug 8/31/2000; 406(6799): 1005-9. PMID: 10984056, DOI: 10.1038/35023008, ISSN: 0028-0836.

Chiang C, Swan RZ, Grachtchouk M, Bolinger M, Litingtung Y, Robertson EK, Cooper MK, Gaffield W, Westphal H, Beachy PA, Dlugosz AA. Essential role for Sonic hedgehog during hair follicle morphogenesis. Dev. Biol. 1999 Jan 1/1/1999; 205(1): 1-9. PMID: 9882493, PII: S0012-1606(98)99103-5, DOI: 10.1006/dbio.1998.9103, ISSN: 0012-1606.

Cooper MK, Porter JA, Young KE, Beachy PA. Teratogen-mediated inhibition of target tissue response to Shh signaling. Science. 1998 Jun 6/5/1998; 280(5369): 1603-7. PMID: 9616123, ISSN: 0036-8075.

Beachy PA, Cooper MK, Young KE, von Kessler DP, Park WJ, Hall TM, Leahy DJ, Porter JA. Multiple roles of cholesterol in hedgehog protein biogenesis and signaling. Cold Spring Harb. Symp. Quant. Biol. 1997; 62: 191-204. PMID: 9598352, ISSN: 0091-7451.

Williams LR, Cooper MK. A new paradigm for postpartum care. J Obstet Gynecol Neonatal Nurs. 1996 Nov; 25(9): 745-9. PMID: 8951111, ISSN: 0884-2175.

Cooper MK, Hamblen-Coyle MJ, Liu X, Rutila JE, Hall JC. Dosage compensation of the period gene in Drosophila melanogaster. Genetics. 1994 Nov; 138(3): 721-32. PMID: 7851769, PMCID: PMC1206222, ISSN: 0016-6731.

Williams LR, Cooper MK. Nurse-managed postpartum home care. J Obstet Gynecol Neonatal Nurs. 1993 Jan; 22(1): 25-31. PMID: 8429411, ISSN: 0884-2175.

Owen ER, Cooper MK, Kark AE. Obesity surgery in the United Kingdom: survey of 970 general surgeons. Ann R Coll Surg Engl. 1991 Jan; 73(1): 36-8. PMID: 1996862, PMCID: PMC2499350, ISSN: 0035-8843.

Roncella S, Ramarli D, Cooper MK, Forni M, Caretto P, Rowe M, Francia di Celle P, Sessarego M, Foà R, Forni G. Establishment of an EBV-positive lymphoblastoid cell line that grows as a lymphoma in nude mice and expresses membrane CD2 molecules. Int. J. Cancer. 1990 Feb 2/15/1990; 45(2): 299-307. PMID: 1968053, ISSN: 0020-7136.