Peptide GPCR Dimers: opportunities for drug design and chemical probe discovery
Carrie Haskell-Luevano
Carrie, University of Minnesota
Peptide GPCR dimerization mechanism(s) of action are becoming increasing relevant to therapeutic drug design approaches and strategies. The melanocortin-4 (MC4R) and melanocortin-3 receptors (MC3R) can function as homo- and heterodimers and appear to possess a synergistic relationship in terms of regulating feeding behavior and energy homeostasis. This presentation will focus on our peptide design approaches and the correlation with in vitro and in vivo data to discover new chemical probes towards understanding the physiological functions of the MC3R and MC4R.
Carrie Haskell-Luevano earned her BS degree in Chemistry from the California State University of Fresno (1990) and her Ph.D. degree in Chemistry (1995) at the University of Arizona under the mentorship of Dr. Victor J. Hruby. Subsequently, and with an NRSA NIH postdoctoral fellowship in hand, Dr. Haskell-Luevano joined the laboratory of Drs. Ira Gantz and “Tachi” Yamada at the University of Michigan for postdoctoral training in G-protein Coupled Receptor pharmacology and molecular biology. Concurrently, she was awarded “visiting scientist” status at Parke-Davis Warner Lambert (ex Pfizer location in Ann Arbor) under the direction of Dr. Christine Humblet within the Basic Structure and Drug Design Department. Subsequent to her training in both these environments, Dr. Haskell-Luevano continued her postdoctoral training at the Vollum Institute in Portland Oregon (OHSU) under the direction of Dr. Roger Cone in neuroscience and molecular pharmacology. During her training at the Vollum, she was awarded the prestigious Burroughs Welcome Career Award in the Biomedical Sciences (only 25 granted that year in the US and Canada) that enabled her to finish up her postdoctoral studies and start an independent research program at the University of Florida Department of Medicinal Chemistry in the College of Pharmacy (1998). At the University of Florida, Dr. Haskell-Luevano was promoted through the ranks of Assistant, Associate, and Full Professor. In 2011 Dr. Haskell-Luevano was recruited to join the University of Minnesota Department of Medicinal Chemistry as Professor and the inaugural Philip S. Portoghese Endowed Chair in Chemical Neuroscience as well as a University of Minnesota Institute for Translational Neuroscience Science Scholar.
Dr. Haskell-Luevano’s research focuses upon the neuroendocrine regulation of food intake and energy homeostasis. Specifically the melanocortin pathway, involving multiple endogenous agonists, antagonists, and GPCRs. Research approaches utilize a variety of multidisciplinary techniques including peptide, small molecule, and combinatorial chemistry synthesis and cell based assays, chemical biology, neuromolecular pharmacology, working with knock out mice, and neuroscience. Dr. Haskell-Luevano’s research has been continuously and generously supported by NIH (NIDDK) as well as the American Heart Association, American Diabetes Association, and the United States-Israel Binational Science Foundation. The Haskell-Luevano laboratory has published over >120 peer-reviewed manuscripts, reviews, book chapters, and conference proceedings. Seven patents have been issued based upon the discovery of novel ligands towards anti-obesity therapeutic applications.
Professional contributions and service to the Medicinal Chemistry scientific community include: Associate Editor for the Journal of Medicinal Chemistry, alternate MEDI division councilor (2015-2017) member of the ACS MEDI Long Range Planning Committee (2010-2013), a charter member of Drug Discovery for the Nervous System (DDNS 2015-2018) the Synthetic and Biological Chemistry-B (SBC-B 2005-2009) NIH Study Sections, as well as regular ad hoc service on several NIH study section panels including DDNS, BNP, SBCB, Member conflict review panels, Molecular Probes, Early-Stage Pharmacological Validation of Novel Targets and Accompanying Pre-Therapeutic Leads for Diseases on Interest to the NIDDK, as well as Endocrine study section panels (2001-present). Dr. Haskell-Luevano has served on several committees associated with the American Peptide Society since 1995 including the Student Affairs Committee (SAC), award committees, as well as Scientific Conference Program contributions. Additionally, she has been elected to serve as a Councilor from 2005-2011 and re-elected for a second term 2011-2017. Dr. Haskell-Luevano served on the Federation of American Societies for Experimental Biology (FASEB) Board of Directors as well as the Excellence in Science Award Committee (2007-2011). Dr. Haskell-Luevano was elected by her peers as Vice co-Chair (2006) and co-Chair (2008) Gordon Research Conference “Peptides, Chemistry & Biology Of”.