OHSU

P. Michael Conn

Conn Fig 1In work conducted over the last 12 years, Conn and his team have identified an underlying biological principle that has dramatically changed scientists' understanding of cellular mutations that result in human disease. He has demonstrated that it is possible to manipulate and redirect the routing of non-functional diabetes, Alzheimer's disease and cataracts. This approach is described at http://en.wikipedia.org/wiki/pharmacoperone

It is becoming well-recognized that mutations of receptors, enzymes and ion channels frequently result in protein misfolding and subsequent retention by the cell's quality control system. Misfolding can result in protein molecules that retain intrinsic function yet become misrouted within the cell and, for reasons of mis-location only, cease to function normally and result in disease. This contrasts with the prior presumption that mutational inactivation always reflects loss of intrinsic function (i.e., a receptor that either fails to recognize ligand or does not couple productively to its effector). Recognition of this alternate concept immediately presents the therapeutic opportunity to correct misrouting and rescue mutants, thereby restoring function and, potentially, curing disease.

Pharmacoperones are small molecules that enter cells, bind specifically to misfolded mutant proteins, correct their folding, and allow them to escape retention by the cellular quality control system. They then route to the plasma membrane (or other site) where they can function normally. The biochemical mehanism of action has been identified and an in vivo proof-of-principle has been accomplished.

In principle, the pharmacoperone rescue approach might apply to a range of human diseases that result from misfolding - among these: cystic fibrosis, hypogonadotropic hypogonadism, nephrogenic diabetes insipidus, retinitis pigmentosa, hypercholesterolemia, cataracts, and neurodegenerative diseases (Huntington's, Alzheimer's, Parkinson's). In the case of particular proteins, this approach has succeeded with a striking number of different mutants, supporting our view that pharmacoperones will become powerful ammunition in our therapeutic arsenal.

 

BIOGRAPHY

 

P. Michael Conn is the Director of the Office of Research Advocacy,  Senior Scientist in Reproductive Sciences & Neuroscience (ONPRC), and Professor of physiology and pharmacology, cell biology and development, and OB/GYN at OHSU, where he served for eleven years as special assistant to the president and as Associate Director of ONPRC. After receiving a B.S. degree and teaching certificate from the University of Michigan (1971), an M.S. from North Carolina State University (1973), and a Ph.D. degree from Baylor College of Medicine (1976), Conn did a fellowship at the National Institute of Child Health and Human Development at NIH, then joined the Department of Pharmacology at Duke University Medical Center, where he was promoted to Associate Professor in 1982.In 1984, he became professor and head of pharmacology at the University of Iowa College of Medicine, a position he held for eleven years.

Conn is the prior Editor-in-Chief of Endocrinology, Molecular and Cellular Neurosciences (founding editor), Methods in Neuroscience, Endocrine, Contemporary Endocrinology, and Reviews in Endocrine and Metabolic Disease, Recent Progress in Hormone Research and prior editor of J Clinical Endocrinology and Metabolism. He is presently the editor of Progress in Molecular Biology and Translational Research. He is the editor of texts in pharmacology (Essentials of Pharmacology), neuroscience (Neuroscience in Medicine), neuroendocrinology (Neuroendocrinology in Physiology and Medicine), endocrinology (Endocrinology: Basic and Clinical Principles) and molecular endocrinology (Principles of Molecular Regulation), as well as more than 100 volumes in endocrinology and neuroscience.

Conn served on the National Board of Medical Examiners, including two years as chairman of the reproduction and endocrinology committee. Conn is best known for his research in the area of the cellular and molecular basis of action of gonadotropin releasing hormone in the pituitary and CNS. He has authored or co-authored nearly 300 publications and 130 books in this area.

The work of his laboratory has been recognized with a MERIT award from the NIH, the J.J. Abel Award of the American Society for Pharmacology and Experimental Therapeutics, Weitzman, Oppenheimer and Ingbar Awards of the Endocrine Society, the National Science Medal of Mexico (the Miguel Aleman Prize), and the Stevenson Award of Canada. In 2004, he received the Oregon State Award for Medical Discovery (Medical Research Foundation of Oregon). His projects have been continuously funded by peer-reviewed federal support since 1976. He is a distinguished alum of Baylor College of Medicine (2012).

Conn is a previous member of the Council for the American Society for Cell Biology and the Endocrine Society and is a prior President of the Endocrine Society, during which time he founded the Hormone Foundation and worked with political leadership to create much of our nation's program in diabetes. He served on the FASEB Board of Directors. Conn's students and fellows have gone on to become leaders in industry and academia. He is an elected member of the Mexican Institute of Medicine and a fellow of the American Association for the Advancement of Science (AAAS).


KEY & RECENT PUBLICATIONS

 

Smithson DC, Janovick JA and Conn PM. (2013) Therapeutic rescue of misfolded/mistrafficked mutants: automation-friendly high throughput assays for identification of pharmacoperone drugs of GPCRs. Methods Enzymol. 521:3-6.

Stewart MD, Deng J, Stewart CA, Mullen R, Wang Y, Lopez S, Serna MK, Huang C-C, Janovick JA, Pask A, Schwartz RJ, Conn PM and Behringer RR. (2012) Mice harboring Gnrhr E90K, a mutation that causes protein misfolding and hypogonadotropic hypogonadism in humans, exhibit testis size reducation and ovulation failure. Mol Endocrinol. 26(11):1847-1856.

Conn PM, Smith E, Hodder P, Janovick JA and Smithson DC. (2013) High throughput screen for pharmacoperons of the vasopressin type 2 receptor. J Biomol Screen. In Press.

Ulloa-Aguirre A, Zarinan T, Dias JA and Conn PM. (2013) Mutations in G protein-coupled receptors that impact receptor trafficking and reproductive function. Mol Cell Endocrinol. In Press.

RESEARCH ADVOCACY PUBLICATIONS

 

Dancet EAF, Kariuki T, Farah IO, Mwenda JM, Chai D, Kyama CM, Nyachieo A, Falconer H, Brannstrom M, Stouffer R, Zelinski M, Conn PM, Parker JV, Fazleabas A, Slayden OV, Mitalipov S, Golos T, Chan A, Strauss J, Hearn J, Else J, Goddeeris B, Hau J, Brasky K and D'Hooghe T. (2013) The role of scientists and clinicians in raising public support for animal research in reproductive biology and medicine. Biol Reprod. 88(2):33.

Conn PM, Parker JV. (2008) The animal research wars. Skeptic Magazine 13(4):19-20.

Conn PM, Parker JV. (2008) The animal research war. FASEBJ. 22(5):1294-1295. PMID: 18450645.

Conn PM. (2008) The war on animal research. The Scientist 22(3):40-46.

Conn PM, Parker JV.  (2008) Warning: animal extremists are dangerous to your health. The Skeptical Inquirer. 32(3):26-31. (Reprinted in: Frazier K, ed, Science Under Siege, Prometheus Books, 2009.)

Conn PM, Parker JV. (2008) Physiologists embedded in the animal research war. Physiologist 51(3):85, 94-95. (Reprinted with permission in the Brazilian Society of Physiology Newsletter, June 2008.) PMID:18595298

Conn PM. (2009) Terrorism in the name of animal rights. The LA Times (syndicated by The LA Times-Washington Post). November 12, 2008. (Reprinted in, Hamilton J, ed. Issues that Concern You: Activism, (ICYAC) 2009. Gale Cengage Learning)

Conn PM, Parker JV. (2008) Awakening the american public. RDS News (UK). Winter 2008, pp4-5.

Conn PM, Parker JV. (2008) Terrorizing medical researchThe Washington Post (syndicated by the LA Times-Washington Post) December 8, 2008 pg a19.

Conn PM, Parker JV. (2009) Neurologists in the cross-hairs, World Neurology 24(2):8.

Conn PM and Parker JV. (2011) America's other most wanted.Wall Street Journal, May 18, 2011 vol. CCLVII no. 115 page a15. 

Parker JV and Conn PM. (2011). From test tube to hypodermic needle: a prescription for educating the public on the value of animal research. The Scientist. 25(11/12):28-29. 


BOOKS

 

Conn PM, Parker JS. (2008) The Animal Research War. Macmillan/Palgrave ISBN-10: 023060014X ISBN-13: 978-0230600140.

Conn PM. (2008) Sourcebook of Models for Biomedical Research. Humana Press.  ISBN13: 978-1-58829-933-8; ISBN10: 978-1-58829-933-3.

Conn PM. (2008) Neuroscience in Medicine. Springer, Totowa, NJ third edition. 

Jennes L, Traurig H, Brueckner JK, Conn PM. (2008) Atlas of the Human Brain (on CD). Springer.

Conn PM (editor-in-chief) (2011) 30 Recent volumes in Progress in Molecular Biology and Translational Science, Elsevier, San Diego, CA.

Conn PM. (2011) Methods in Enzymology, vol. 489-491, The Unfolded Protein Response and Cellular Stress, Part A-C. Academic Press, New York. ISBN: 978-0-12-385116-1

Conn PM (editor) (2011) Reliable Lab Solutions, Essential Ion Channel Methods. Science Press (Elsevier), China. ISBN: 978-7-03-030602-9.

Conn PM (2012) Methods in Enzymology, vol. 504-506, Imaging and Spectroscopy of Living Cells, Part A-C. Academic Press, New York. (In press).

 

See a full listing of Dr. Conn's publications