Pharmaceutical Sciences Research and Scholarship
Hanley N. Abramson: During the wet bench research phase of his career, Dr. Abramson was engaged in the design and synthesis of analogs of naturally-occurring bioactive compounds; these endeavors resulted in publications describing work on cardiotonic and estrogenic steroids, azabiotin (the nitrogen isostere of the vitamin biotin), and antimicrobial pyrones related to nectriapyrone; recent interests focus on approaches to the design of new anthracyclines with the aim of lowering the cardiotoxic potential of these clinically useful antitumor agents through reduced redox cycling.
Deepak Bhalla: Research is aimed at developing and characterizing animal models that simulate health consequences of air pollutants such as ozone (O3) and cigarette smoke in normal populations and in individuals whose lungs are compromised by a co-pollutant, infection or prior inflammation. While the toxicity studies determine the adverse effects of air pollutants in a compromised lung by utilizing sensitive assays, the mechanistic studies identify major factors that influence the inflammatory response and disease pathogenesis. The intervention strategies are aimed at limiting neutrophil recruitment in the lung by antibodies and inhibitors specific for chemotactic signals, cell attachment and cell migration.
Randall L.Commissaris: The overall aim of studies in Dr. Commissaris' laboratory is to further our understanding of the neuroanatomical sites and neuropharmacological mechanisms for the actions of drugs and other chemicals on behavior. For many years, Dr. Commissaris' laboratory has been studying the effects of drugs of abuse and drugs used in psychiatry, with a particular emphasis on drugs used in the treatment of anxiety and depression. More recently, Dr. Commissaris' laboratory has begun studies investigating the behavioral effects of in utero and perinatal exposure to ethanol and environmental compounds such as lead.
George B. Corcoran: Multidisciplinary and translational research interests focus on cellular injury and cell death, as well as factors governing drug and chemical-induced injuries, including drug metabolism and nutrition. Approaches designed to translate basic discoveries to improve human health and safety involve integrated in vivo models, cellular and molecular biology, pharmacokinetics, synthetic chemistry, and retrospective and prospective clinical investigation of human volunteers and patients. Specific areas of investigation include cell death by necrosis and apoptosis, the role of DNA damage in acute cell death, drug and chemical injury to the liver, role of nutrition and obesity in drug and chemical injury, drug biotransformation including by CYPs, and particularly the toxicity of acetaminophen (paracetamol).
Aloke K. Dutta: Our research integrates medicinal chemistry, neuropharmacology, computational chemistry and molecular biology not only to understand the mechanism of action of novel CNS active molecules but also to advance promising leads to preclinical studies. We focus on discovery of novel drugs for the CNS to explore their potential therapeutic application in several neuro-disorders like Parkinson’s disease, depression and drug addiction. Specifically, novel molecules, designed through rational drug design and computational studies, are developed routinely to target monoamine transporters and receptors systems either specifically or non-specifically to produce desired pharmacological outcome. In PD research area we are focused on development of bi or poly-functional molecules to produce neuroprotective treatment agents. In the depression area, we have developed novel triple uptake inhibitors as promising new generation antidepressants. Our research is supported by multiple NIH R01 grants.
Steven M. Firestine: Chemical biology and medicinal chemistry focused on the discovery and elucidation of antiinfective agents. Specific areas of interest include the development of agents targeted to de novo purine biosynthesis, the creation of membrane active antibiotics and the discovery of novel peptidomimetics to inhibit DNA replication in cytomegalovirus.
Fusao Hirata: Our group is the first to characterize annexin A1, a 37K Da protein previously referred as lipomodulin or lipocortin I. This protein mimics some, if not all, of the actions of glucocorticoids, e.g., anti-inflammation and immunosuppression, by inhibiting phospholipase A2. On the other hand, this protein is a major substrate of the oncogenic tyrosine kinases such as c-met and c-src, thereby being involved in cell proliferation and differentiation, but its role in signal transduction remains poorly understood. Our current research deals with translocation and modifications of annexin A1 in nuclei to explore its role in carcinogenesis and cell transformation.
Anjaneyulu Kowluru: Our diabetes research is aimed at: [i] understanding the mechanism[s] underlying glucose-stimulated insulin secretion from normal beta cells. The goal is to identify specific genes that must be regulated by glucose to induce insulin secretion; [ii] identifying specific defects in the glucose-signaling pathways within the beta cell in type 2 diabetes with a goal to identify novel drug targets to rectify these in the diabetic beta cell; and [iii] deciphering mechanisms responsible for autoimmune destruction of the beta cell death leading to the onset of type 1 diabetes. Our goal is to develop beta cells that are resistant to immune attack for use in transplantation treatment of Type 1 diabetes.
Robert T. Louis-Ferdinand: Mechanisms of adaptive responses following sub-acute and chronic exposure to toxicants and therapeutic agents; environmental influences on the development of toxicity.
David Oupicky: Research interests focused on the application of nanotechnology in medicine. Application of interdisciplinary approaches to the design of “smart” nanosized drug and gene delivery systems capable of changing their biophysical and biological properties and behavior in response to a range of endogenous and external stimuli. Specific areas of investigation include redox-responsive nanoparticles, nanoporous drug delivery systems, and thin multilayered DNA films for localized gene therapy.
David K. Pitts: The understanding of the physiological and pharmacological properties of central monoaminergic neurons is of general interest, especially as this pertains to neurological and psychiatric diseases and disorders. One focus area examines the effects of xenobiotic exposure on the postnatal development of monoaminergic neurons. Another focus area is the pharmacological characterization of novel drugs that have potential therapeutic actions involving monoaminergic neurons. The study of monoaminergic neurons utilizes electrophysiological techniques, immunohistochemistry, and microdialysis.
Philip L. Pokorski: Clinical interdisciplinary research involving polypharmacy pharmacokinetics and mechanisms; a related interest is the toxicology of drugs of abuse and pharmaceutical agents in forensic deaths; cellular mechanisms of pathologic and disease processes which account for specific symptoms of disease; past research interests include heavy metals toxicology and therapeutic detoxification mechanisms of 2,3-dimercaptosuccinic acid (Succimer, Chemet).
Joshua J. Reineke: Nanoparticle drug delivery systems provide protection and enhanced uptake of therapeutic agents allowing efficient, non-parenternal drug delivery with targeted and sustained release potential. Cellular and molecular mechanisms of nanoparticle uptake and transit are poorly understood. My research utilizes quantitative uptake studies, pathway-specific inhibition and molecular biology techniques to determine mechanisms involved in internalization and transit following pulmonary administration. Biodistribution profile data enables rational design of nanoparticles for organ- and/or pathology-directed therapies. These studies also address the need for understanding nanoparticle disposition in the field of nanotoxicology and may lend greater understanding to the development of lung pathologies.
Duska M. Separovic: Our research interests are focused on studying the molecular mechanisms underlying cell death evoked by oxidative stress after photodynamic therapy (PDT), a cancer treatment modality. Our long-term goal is to potentiate the efficacy of PDT for cancer treatment. Specifically, we investigate the involvement of sphingolipids in cell death post-PDT. The significance of our research is in that it should reveal: new molecular targets that will lend themselves to therapeutic interventions; new sphingolipid analogs that advance PDT therapeutic successes.
David M. Thomas: Research interests focus on the cellular and molecular processes affected by methamphetamine and other neurotoxic drugs of abuse. Microglia, the central nervous system equivalent of systemic macrophages, have attracted considerable attention for their role in mediating neural damage. Recent data from our lab demonstrate that methamphetamine induces microglial activation prior to the advent of dopaminergic nerve terminal damage associated with this drug. These results suggest that the activation of these cells may exacerbate methamphetamine neurotoxicity. Approaches designed to elucidate the role of microglia in this process include in vivo and cell culture models, as well as a wide variety of cellular and molecular biology techniques .
Henry C. Wormser: Synthesis, antimicrobial and cytotoxic screening of a number of 1,4-dihydroxy and 1,4-diamino anthraquinones as well as DNA binding studies of synthetic anthraquinones related to antineoplastic anthracyclines. Structure determination of natural products of biological interest with the intent to develop and synthesize more active analogs. Involvement in the development of the original Wayne State University College of Pharmacy add-on PharmD curriculum and of the current Physician Assistant Studies program.
Woster, Patrick: Research in the Woster laboratory involves the synthesis and preliminary bioevaluation of new therapeutic agents. Ongoing projects include synthesis of guanidine, biguanide, peptidomimetic and lysine analogue inhibitors of lysine-specific demethylase (LSD1), an enzyme involved in the aberrant silencing of tumor suppressor genes; polyaminohydroxamic acid and polyaminobenzamide inhibitors of histone deacetylase isoforms as antitumor agents or agents for the treatment of type 1 diabetes; polyamine-metal complexes with Pt, Re, Rh and Ru that crosslink DNA, and are effective against breast tumors; antimalarial peptidomimetic analogues that act as mechanism-based inhibitors of plasmepsin II, an aspartyl protease drug target in Plasmodium; polyamine analogues as potential antitrypanosomal agents.