Professor of Molecular Physiology and Biophysics
Professor of Molecular Physiology and Biophysics
Over the past 44 years Dr. Cherrington has carried out important metabolic research using the conscious dog as a model. During that period he, his colleagues and trainees developed an array of unique surgical approaches (trans-hepatic, renal, gut, head, limb cannulation, 3rd ventricle cannulation, liver and renal denervation, carotid body resection, adrenalectomy, pancreatectomy and duodenal bypass) which when combined with clamping (hormone, metabolite) techniques have allowed the performance of experiments not possible anywhere else in the world. Using the dog, which has high translation value to the human, the Cherrington lab can measure whole body metabolism at the same time as organ balance and molecular signaling (using biopsies). In addition they developed a model of T1DM using alloxan, as well as a model of T2DM using diet manipulation. Using this array of techniques and models the Cherrington lab has assessed the way in which hormones, neural mediators, and metabolites interact to control hepatic glucose production (glycogenolysis/gluconeogenesis) and liver glucose uptake (and storage) in the conscious dog. Their work has resulted in almost 300 peer reviewed papers, as well as 87 review articles. It has been recognized with numerous honors including the Lilly and the Banting Awards for research from the ADA and the Rumbough Award for research from the JDRF.
About twelve years ago Dr. Cherrington decided to devote a significant portion of his research effort to helping expedite drug discovery and device development within the pharmaceutical sector. He set up a structure that provided four opportunities for interaction with pharma and bio-tech partners, 1) consulting, 2) direct help with experiments at a given pharma site, 3) contract research within Vanderbilt and lastly 4) contract research with a 3rd party CRO. This menu of services was based on his many years of experience in the field, as well as the ability to carry out unique proof of concept studies utilizing his conscious dog models. He has now worked with a majority of the major pharmaceutical companies (Merck, Novo Nordisk, Eli Lilly, Sanofi, GlaxoSmithKline, Bristol Myers Squib, Hoffman LaRoche, Biocon, Pfizer, Gilead, Boehringer Ingelheim, Boston Scientific, Abbott, Amylin, Takeda, Tanabe) and many small bio-techs (Abvance, Calibr, Fractyl, Galvani, Metavention, NuSirt, Sensulin, Metabasis, Inhale Therapeutics, Silver Lake, Thermalin, Thetis, VTv Therapeutics, Viacyte, Viking, Zafgen, NGM, OSI). The work performed in Cherrington’s lab was often important in shaping the direction of internal programs and in establishing the credibility of a particular approach both within and without the company. Many of the study outcomes have now been published in peer reviewed journals. Of particular note is the work carried out to investigate novel insulin analogues (Biocon – oral insulin; Novo Nordisk – hepatic-preferential insulin; Eli Lilly – hepatopreferential insulin; Thermalin – ultra rapid insulin; Pfizer – inhaled insulin; Merck – glucose responsive insulin). Likewise, work with GLP-1 (Amylin), incretin mimetics (Amylin) and DPPIV (BMS) inhibitors helped advance that class of compounds. More recently the lab has been working in the electroceutical field (Boston Scientific, Galvani, and Metavention) to establish the feasibility of using nerve stimulation or blockade to alter metabolic regulation in vivo. Finally, it should be noted that Dr. Cherrington’s lab has also carried out studies focused on SGLT-2 inhibitors, 11betaHSD 1 blockers, glucagon receptor antagonists, as well as glucokinase activators. It is worth noting that his collaborations are international, such that he has worked with companies around the world including those based in the USA, Germany, France, Denmark, Japan, Switzerland and India. By offering his expertise and unique models to others he has provided important input into decision making within the pharmaceutical and bio-tech world.
Alexander (Zan) Fleming
Dr. Alexander Fleming received his M.D. and internal medicine training from Emory, fellowship training in endocrinology at Vanderbilt and metabolism at National Institutes of Health, where he was a senior fellow. From 1986-98 Dr. Fleming served as reviewer and supervisory medical officer at the US Food and Drug Administration. He acquired extensive clinical experience and regulatory responsibility in the therapeutic areas of diabetes, other metabolic and endocrine disorders, growth and development, nutrition, lipid-lowering compounds, orphan drug indications, and reproductive indications. He led reviews of landmark approvals including those of the first statin, insulin analog, metformin, PPAR-agonist, and growth hormone for non-GH deficiency indications. He was responsible for the regulation of the earliest biotech products including human insulin and growth hormone. He helped to shape a number of FDA policies and practices related to therapeutic review and regulatory communication.
His regulatory and technical expertise has been requested in numerous international settings including the World Health Organization, where he was assigned during 1991-92. Dr. Fleming was a member of the expert working groups on Good Clinical Practices and General Considerations for Clinical Trials of the International Conference on Harmonization (ICH) and participated on other ICH committees including the Common Technical Document working group.
He was also the founder and editor in chief of the Virtual Journal of Drug Evaluation, of FDA's Center for Drug Evaluation and Research (CDER), a major contributor to FDA's Good Review Practice (GRP) initiative, and chair of the committee responsible for education and training at CDER. He conceived and led the first FDA pilot project to utilize the internet for regulatory communication. Dr. Fleming is lead author of the book, “Optimizing Development of Therapies for Diabetes.” He has frequently published scientific articles and book chapters, the most recent chapter, Regulatory Considerations for Early Clinical Development, is in Translational Research Methods for Diabetes, Obesity and Cardiometabolic Drug Development, published by Springer in January 2015. He has been a member of number corporate and professional society advisory boards. The most recent is the joint European Association for the Study of Diabetes and American Diabetes Association working group on insulin pump safety.
Dr. Fleming founded Kinexum, a strategic advisory firm in 2003 and continues to serve as its chief executive officer.