Our research focuses on developing new treatments for depression based on subtype-selective modulation of phosphodiesterase 4B (PDE4B). PDE4 in neurons is responsible for the hydrolysis of cAMP. We and our colleagues recently described the protein structure of a key PDE4 regulatory domain known as UCR2. This structural insight allowed us to design allosteric modulators of PDE4 that close UCR2 over the active site. PDE4 allosteric modulators have improved efficacy and tolerability over previous compounds that simply inhibit the enzyme by binding in the active site.
Dr. Mark Gurney is the Founder & President of Tetra Discovery Partners LLC. Dr. Gurney received his PhD from the California Institute of Technology and his MBA from the Kellogg Graduate School of Management, Northwestern University. He was on the faculty of The University of Chicago and Northwestern University Medical Schools before moving to the pharmaceutical industry where he was Director, Genomics Research at Pharmacia Upjohn and Senior Vice President of Drug Discovery and Development for deCODE genetics, Inc. While at Northwestern, Dr. Gurney developed the SOD1-G93A transgenic model of amyotrophic lateral sclerosis (ALS) [Science, 264: 1772-1775, 1994]. With colleagues at Pharmacia Corporation, he discovered the Alzheimer’s disease beta-secretase (BACE1) using a comparative genomics strategy [Nature 402:533-537, 1999]. While at deCODE genetics, Inc. he developed a novel anti-platelet targeting the EP3 receptor for prostaglandin E2 [ACS Chem Biol. 4:115-126, 2009], discovered allosteric modulators of phosphodiesterase 4 (PDE4) [Nat. Biotech. 28:63-70, 2010], and developed decapping scavenger enzyme (DcpS) inhibitors as novel therapeutic agents for treating spinal muscular atrophy [ACS Chem Biol. 3:711-22, 2008]. Dr. Gurney invests in early stage West Michigan Technology companies through the Grand Angels. He also advises the Michigan Accelerator Fund-1 on investments in West Michigan life sciences companies.
In March 2012 Mark was named one of two leading doctors in the creation of patents to treat Alzheimer’s disease. Visit the blog for more information on Marks work towards treatments of Alzheimer’s disease.
Professor O’Donnell a long-standing interest and expertise in neuropsychopharmacology, with a particular focus on relating neurochemical/molecular effects of drugs to their effects on behavior. His research focuses on the role of noradrenergic neurons, beta adrenergic receptor–effector systems, and cyclic AMP phosphodiesterase in mediating the actions of antidepressant drugs and in behavioral regulation. With Professor Hanting Zhang, also at West Viriginia University, he has shown the importance of PDE4 as a novel drug target for treatment of depression. Professor O’Donnell serves as Assistant Vice President in the Health Sciences Center of West Virginia University, Assistant Dean for Research in the School of Medicine, and Vice Chair for Research in the Department of Behavioral Medicine and Psychiatry. Professor O’Donnell collaborates with the company on preclinical studies of drugs in animal models of depression and of learning and memory.
Professor Hagen has considerable experience with medicinal chemistry and the design and synthesis of compounds to treat psychiatric disease. He has 20+ years of experience in the pharmaceutical industry having held positions of increasing responsibility at Searle, Pharmacia, Pfizer and Decode Chemistry. A faculty member of the Department of Chemistry at Northern Illinois University, Professor Hagen research interests are at the interface of chemistry and biology. The focus of his academic laboratory is on structure-based design and synthesis of small molecules that can modulate essential pathways of infectious disease organisms with an emphasis on small molecule-protein interactions and target specificity. His laboratory utilizes fragment-based screening, de novo design, the design and synthesis of versatile fragment building blocks from natural products, and construction of fragment libraries to explore enzyme selectivity. Professor Hagen advises the company on the structure-guided design of PDE4 allosteric inhibitors.
Dr. Stewart co-founded Emerald BioStructures in 1998 and led the growth of Emerald as a business unit within two publicly traded companies (MCLS and DCGN) and the successful spin out from deCODE genetics in November 2009. During his tenure, Dr. Stewart oversaw Emerald’s research that supported the discovery of eight investigational new drug molecules for clients’ projects. Dr. Stewart is currently Senior Director, Alliances for the Allen Brain Institute in which role he fosters brain science collaborations with pharmaceutical and biotechnology companies, government, foundations, and academia that leverage the incredible research platforms at the Allen Institute. Dr. Stewart allows Tetra to present his Twitter feed regarding new treatments for traumatic brain injury and other neurological disorders on the company website.