University of Michigan Chemical Biology Doctoral Program
We apply chemical principles, particularly those of organic chemistry, to solve problems focused on human health. Over the past few years, my group has worked in several areas including anti-DNA autoantibody structure and function, and the identification of novel molecular targets and small molecules for the treatment of autoimmune diseases and cancer.
Anti-DNA autoantibodies are a hallmark of the autoimmune disorder systemic lupus erythematosus, and mediate a kidney inflammation that can be fatal. However, the DNA molecules recognized by anti-DNA and their binding properties remain poorly understood. We have conducted chemical, biochemical, and genetic studies to investigate the interaction of pathogenic anti-DNA with ssDNA. Ultimately, we hope that characterization of anti-DNA•DNA interactions will provide insight to advance diagnosis of lupus.
In a second area, we are identifying new targets and small molecules for the treatment of autoimmune diseases and cancer. Current therapies for these disorders employ cytotoxic agents that have limited efficacy and serious side effects. Using diversity-oriented synthesis, we identified a class of non-anxiolytic, pro-apoptotic benzodiazepines that treat disease in animal models of lupus. These compounds selectively kill pathogenic lymphocytes, and unlike current therapies, they are not adversely immunosuppressive.
We are now exploring the signals that arise as a result of target binding. These studies should help to uncover the basis for the selectivity displayed by these compounds and help to delineate the specific signals that initiate apoptosis. Additionally, the target of our benzodiazepines is a relatively uncharacterized component of the mitochondrial F1F0-ATPase, and only limited information about its function within the enzyme is available. Therefore, we are also using these compounds to probe the function of this protein within the F1F0-ATPase using a combination of biology, organic synthesis, kinetics, and structural studies of target•drug interactions.
We have discovered that our benzodiazepines circumvent the major mechanisms cancer cells use to become resistant to therapy. Based on our understanding of the factors regulating the cellular sensitivity to our agents, we plan to examine the effects of these compounds on resistant cancers. These experiments should demonstrate additional uses for these molecules and reveal new pathways and targets for additional drug discovery.
Gary D. Glick obtained his Ph.D. degree from Columbia University in 1988 studying organic chemistry with W. Clark Still. After completing an NIH postdoctoral fellowship at Harvard University in the laboratory of Jeremy R. Knowles, he joined the chemistry faculty at the University of Michigan in Ann Arbor in 1990, where he presently holds the Werner E. Bachmann chair and is a professor in the Department of Biological Chemistry at the University of Michigan Medical School. During his tenure at Michigan, Dr. Glick founded the Chemical Biology Doctoral Program, served on numerous local and national boards and committees, and he is presently Editor-in-Chief of Biopolymers, a leading journal publishing in the areas of biochemistry and biophysics.
Dr. Glick’s research currently focuses on metabolic control in the immune system and the development of new drugs for the treatment of autoimmunity and cancer. He is the author of over 100 peer-reviewed papers and the inventor on 27 issued U.S. patents. His scientific contributions have been recognized with a number of different awards including, an Arthritis Investigator Award from the National Arthritis Foundation, a Junior Faculty Research Award from the American Cancer Society, a Young Investigator Award from the National Science Foundation, a Camille Dreyfus Teacher-Scholar Award, a Research Fellowship from the Alfred P. Sloan Foundation, and he is a Fellow of the American Association for the Advancement of Science.
In 2006, Dr. Glick founded Lycera Corp. to discovery breakthrough medicines for autoimmune diseases and cancer. Serving first as president, then as chief science officer, Dr. Glick recruited a team of over 20 chemists, immunologists, and physician-scientists and raised over $40 MM in equity financing to support the company. Under his direction and leadership, Lycera initiated six innovative discovery programs; partnered three of these programs with Merck & Co. in deals collectively valued at over $600 MM; advanced LYC-30937, a modulator of the mitochondrial ATPase based directly on research from his academic lab, into clinical trials for inflammatory bowel disease; and established Lycera’s immune-oncology platform.