The department has a diverse group of primary and secondary faculty interested in drug discovery. Collaborations between drug discovery, structural and synthetic/computational chemistry groups are encouraged, and there are many exciting inter:disciplinary studies ongoing. The department offers a unique collaborative environment for prospective graduate students to find disease cures as a part of Drug Discovery program.
The research of the primary and secondary faculty have interests in drug discovery are listed below along with a short description of their work.
|Karen Anderson - The research in our laboratory is directed toward understanding molecular mechanism of clinically important antimicrobial, anticancer, and antiviral molecular targets with the ultimate goal of developing more effective therapies. Key enzyme targets for the development of therapeutics include - KDO8P synthase (an important target for new antibacterials) and a bifunctional thymidylate synthase:dihydrofolate reductase (TS:DHFR) enzyme from parasites (a target for new antiparasitic drugs). Also ongoing are studies to understanding the molecular mechanisms of normal and aberrant protein signaling and the effects of selectively guided anticancer drugs such as Iressa and Gleevec. Important molecular targets include EGFR, HER:2, PDGFR, and c-kit receptor tyrosine kinases. Another key area of focus involves investigating the mechanisms of HIV reverse transcriptase as well as drug resistance and toxicity that may ultimately aid in the design of better therapeutic agents for the treatment of AIDS.|
|Anton Bennett - The focus of our laboratory is on the physiological and pathophysiological role of the protein tyrosine phosphatases (PTPs). It is now established that protein tyrosine kinases can serve as therapeutic targets against cancer and potentially other diseases. PTPs, which function in the same signaling pathways that are regulated by PTKs, represent an emerging area for drug discovery. We are particularly interested in identifying small molecule inhibitors to PTPs that are involved in metabolic and skeletal muscle diseases.|
|Yung-Chi Cheng - Our laboratory is interested in cancer and viral chemotherapy. This includes the discovery of new drug entities. Three clinically used antiviral drugs were discovered in my laboratory, five others are at different stages of clinical development, and four more are still at the preclinical stage of development. The approaches taken for the discovery of new drugs are target oriented approaches toward unique virus gene products and/or cancer replication.|
|Craig Crews - The Crews lab explores novel drug target identification/validation through natural product mode of action studies. Examples of these efforts include the identification of methionine aminopeptidase 2 (MetAP:2) as a new anti:angiogenic drug target and the discovery of a new class of proteasome inhibitors, one of which served as the basis for Carfilzomib, a Phase III drug candidate for multiple myeloma.|
|Jonathan Ellman - Research efforts are focused on the development of efficient, systematic chemical tools to establish protein function through the design and synthesis of small molecule libraries targeting protein families. In addition, a major emphasis is placed on the development of practical and general new synthetic methods, in particular, methods for the asymmetric synthesis of amines and the development of synthetic applications of C-H activation.|
|Len Kaczmarek - Our laboratory is interested in studying ion channels as possible molecular targets for the design of new therapies. One area of focus is the Slack potassium ion channel as a therapeutic target for Fragile X Syndrome. Individuals with Fragile X syndrome, the most common form of inherited intellectual disability, have a range of perceptual processing deficits. In part this may result from altered neuronal potassium channels. In particular the Slack potassium channel forms a complex with Fragile X Mental Retardation Protein (FMRP), which is missing in Fragile X syndrome, leading to lowered Slack currents and altered neuronal excitability. Our laboratory is developing a range of compounds that can activate Slack channels. The discovery of potent and selective compounds will provide a strong impetus for the evaluation of Slack activators as novel therapeutic agents.|
|Elias Lolis - My laboratory is interested in finding inhibitors to cytokines and chemokines important for inflammation and cancer. Some of our targets are also parasitic cytokine mimics that evade the immune response and important to human health. We use an iterative cycle of high throughput screening, X:ray crystallography, rational drug design, and structural:activity relationships. We also use molecular biology to discover peptides that are agonists and antagonists.|
|Marina Picciotto - Depression is a debilitating illness that is highly prevalent in the United States and up to 50% of patients with major depression are non:responsive to current antidepressant medications. Based on our basic science studies of the role of acetylcholine in pathways underlying depression:like behavior in rodents, our laboratory has identified nicotinic acetylcholine receptors (nAChRs) as a key target for development of novel antidepressant medications. We have established collaborations with a chemist (Dr. Daniela Gundisch, University of Hawaii) who has synthesized a number of new nicotinic partial agonists that target specific subtypes of nAChRs. In collaboration with an electrophysiologist (Dr. Roger Papke, University of Florida) we have characterized the selectivity of these compounds and our lab has shown that they are effective in animal models of antidepressant:efficacy. As a proof of principle, we have shown that nicotinic agents already approved for use in human subjects are also effective in these animal models (mecamylamine (Inversine) and varenicline (Chantix)) and these medications have now been used successfully in human clinical trials as add:on medications to classical antidepressants targeting the serotonin transporter (SSRIs). We hope that the more selective compounds we are developing will be effective for patients who do not respond to existing medications and that they will have fewer side effects than non:selective nicotinic compounds.|
|Joseph Schlessinger - Our laboratory is using genetic, structural and biochemical approaches to identity novel targets in the action of normal and oncogenic RTKs that may function as "Achilles heels" and can be utilized for drug discovery. We are also using structure guided drug discovery approach to identify drugs that will overcome the resistance that develops in cancer patients treated with kinase inhibitors such as Gleevec, Iressa, Sutent and Nexavar.|
|David Spiegel - The Spiegel Laboratory is interested in integrating synthetic chemistry, immunology, and cell biology in the design of novel small:molecule immunotherapeutics. In particular, the lab is working toward a class of antibody-recruiting small molecules (ARMs) that are capable of enhancing recognition of diverse pathogens by the human immune system. The ARM technology represents an entirely novel therapeutic modality that has the potential to combine benefits of both antibody:based and traditional small-molecule:based strategies. For example, ARMs exhibit high specificity, minimal off:target cytotoxicity, and favorable pharmacokinetics, and also have the potential to initiate long:lasting anti:pathogen immunity. We have successfully employed this approach in targeting both HIV and prostate cancer, and believe that it can be applied quite generally toward other diseases as well.|
|Ben Turk - We take an interdisciplinary approach combining structural biology, combinatorial library screening, biochemistry, and cell biology to understand fundamentally how protein kinases target specific protein substrates in living cells. Based on this work we are pursuing strategies for identifying novel classes of small molecule kinase inhibitors that function by disrupting interactions with substrates. We are particularly interested in kinases that are critical for cell growth, proliferation and survival that constitute established and exploratory targets for cancer therapy.|
|Stephen Waxman - Voltage-sensitive sodium channels as molecular targets. Neuropathic pain.|
|Dan Wu - We study the signaling mechanisms activated by chemoattractants and Wnts and how these signaling mechanisms function in physiological and pathophysiological processes including inflammation, atherosclerosis, arthritis, tumorigenesis, metabolic and bone diseases. Small molecules and biologicals are being developed to alter these signaling pathways for target validation and therapeutic development.|