Faculty Participating in the Integrated BS/MS Biochemistry with Emphasis on Medicinal Chemisry
Mayo Clinic Scottsdale:
Researchers:
- Joseph C. Loftus;
PhD;
- Christopher A. Lipinski, MD;
- Daniel Riggs, PhD;
- James Allen, PhD (ASU);
- Michael C. Berens, PhD;
- Nhan Tran, PhD;
- Nathalie Meurice, PhD (TGen);
- Gary Flynn, PhD (BIO5)
Contact information: Christopher A. Lipinski, MD; Mayo Collaborative Research Building
Mayo Clinic Arizona; 13400 East Shea Blvd.; Scottsdale, AZ 85259; (480) 301-5653 Lipinski.Christopher@mayo.edu
Research Descripton: Glioblastoma multiforme (GBM) is the most common form of malignant brain tumor and is extraordinarily aggressive. Patients are typically diagnosed at younger ages than seen with other tumor types (mean ~50 years of age) and the average survival from diagnosis is approximately 1 year despite currently available therapy. The major pathobiological feature of GBM is invasion of tumor cells away from the central tumor mass. These cells are particularly problematic as they are not removed by surgical resection and are resistant to radiation and current chemotherapy. Our multidisciplinary group is comprised of clinicians, cancer biologists, molecular biologists, structural chemists, computational chemists, and medicinal chemists. The focus area of the group is on discovery of drugs which prevention of GBM cell invasion and as a potential result, sensitizing these cells to other cytotoxic strategies. These efforts have resulted in: (1) identification of a small molecule lead compound which targets a non-catalytic site of the pro-invasive kinase, Pyk2 and inhibits GBM cell migration, (2) generation of a biological molecule (monoclonal antibody) and single-chain variable fragment (scFv) which inhibit GBM cell migration, and (3) therapeutic inhibitory siRNAs. These therapeutic leads are currently advancing though preclinical evaluation and optimization stages of development.
Barrow Neurological Institute
Researchers:
- Dr Ronald J. Lukas, Ph.D. ,
Contact Information: Ronald J. Lukas, Ph.D, Senior Staff Scientist, Division of Neurobiology , Director, Laboratory of Neurochemistry : Barrow Neurological Institute , 350 West Thomas Road , Phoenix, Arizona 85013 . (602)-406-3399 ; rlukas@chw.edu
http://www.thebarrow.org : research : basic research : neurochemistry
Research Description: The Lukas laboratory predominantly engages in studies of nicotinic acetylcholine receptors. These receptors play important roles throughout the brain and body in mediation of chemical signaling by the natural chemical messenger, acetylcholine. They also mediate effects of nicotine. Their broad physiological roles are matched by their suspected or known involvement in a variety of diseases, including Alzheimer's, schizophrenia, and epilepsy. Moreover, receptor responses to nicotine are involved in nicotine dependence and consequent tobacco-related diseases including cancers and vascular disorders. The laboratory is involved in nicotinic drug discovery efforts as well as in efforts to develop superior research tools for nicotinic receptor studies.
Midwestern University
- Dr. Hugo R. Arias
Associate Professor
Contact Information: Hugo R. Arias, Associate Professor, Department of Pharmaceutical Sciences, Midwestern University, 19555 N 59th Ave., Glendale, AZ 85308. Phone: (623)572-3589; FAX: (623) 857-3550; Email harias@midwestern.edu
Research Description:
Structural and functional characterization of nicotinic acetylcholine receptors.
The scientific interest of my laboratory is centered on the topological localization of binding sites and mechanisms of action for noncompetitive antagonists of potential medical interest in nicotinic acetylcholine receptors (AChRs), archetypes of the Cys-loop ligand-gated ion channel superfamily. These studies are of great importance for the understanding of the structure and functions of this receptor superfamily which mediates synaptic transmission in the nervous system and contributes to higher-order brain mechanisms such as learning and memory, as well as for the understanding of the origin of several neurological disorders including Alzheimer’s disease, depression, and drug addiction, to name some of the most important diseases. More specifically, we are interested in determining the binding site locations and inhibitory mechanisms for structurally different antidepressants, for benzylidene-anabaseine derivatives (in clinical trial for the treatment of Alzheimer’s disease- and schizophrenia-related dementias), and for ibogaine congeners (potential anti-addictive drugs), in muscle-type (e.g., Torpedo and mice AChRs) and neuronal-type AChRs (e.g., human α3β4, human α7, and human α4β2 subtypes, each expressed in HEK293 cells), when the receptor is in different conformational states. To perform these studies we are using a combination of state-of-the-art approaches including state-dependent radioligand binding, structure-activity relationship studies, quantitative fluorescence spectroscopy, photoaffinity labeling, electrophysiology, structural modeling and molecular docking, and animal behavior in mutant mice.
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