The Metallotherapeutics Research Center is a dynamic multi-disciplinary research core comprising faculty from across the University System of Maryland and institutions throughout the Baltimore-Washington area.
Research themes cover a broad spectrum under the umbrella of drug discovery, metal-based drug development, and evaluation of metallotherapeutic agents. Themes of specific focus include:
- Infection and immunity
- Antimicrobial drug development
- Role of metals in inflammation and hereditary human disease
- Environmental impact of toxic metals on human health
Richard Dalby: Optimization of drug delivery to the lung and nose Including the development and evaluation of novel pulmonary and nasal delivery devices. Current interests in the area of metal systems includes the analysis and impact of toxic metal in e-cigarette vapor.
Daniel Deredge: Application of HDX-MS and computational methods with other structural MS methods in the study of biological systems. Projects with a metallotherapeutic focus include viral RNA polymerases and bacterial heme uptake proteins important for pathogenesis.
Steven Fletcher: Disruption of dysregulated protein-protein and protein-DNA interactions involved in cancer with synthetic small-molecule mimetics of protein secondary structure, with an interest in zinc-kinases and the zinc-finger family of proteins.
Stephen Hoag: Formulation of immediate and controlled release of small molecules, biologics and mathematical modeling of mass transport in hydrogels, such as the heterogenous calcium-alginate polymers.
Maureen Kane: Development of new bio-analytical technologies for quantitative profiling of metabolites and proteins. Areas of focus include the role of retinoid retinoid metabolism in cancer, diabetes, obesity, and inflammation. Dr. Kane collaborates with Drs. Oglesby-Sherrouse and Wilks in understanding the role of iron and heme on secondary metabolism and regulation. Dr. Kane is also the executive director of the Mass Spectrometry Center.
Alexander MacKerell: Computational and theoretical studies of biological, pharmaceutical and chemical systems. His interest in metal systems includes collaboration with Drs. Wilks, Oglesby-Sherrouse and Xue on the identification, design and synthesis of novel strategies targeting heme and iron metabolism in P. aeruginosa. Dr. MacKerell is also the director of the Computer-Aided Drug Design Center (CADD).
Sarah Michel: Investigation of metalloregulatory proteins that recognize and regulate DNA and RNA, and participate in inflammation, cancer, normal neuronal development, and immune response. Recent interests include metal speciation in biological systems. Dr. Michel is co-director of the Metallotherapeutics Research Center.
Amanda Oglesby: Understanding how iron regulatory systems affect the physiology and virulence capacity of bacterial pathogens. Genetic, biochemical, and analytical approaches are used to understand the mechanisms guiding iron regulation, as well as the impact of these regulatory systems on pathogenesis. In these efforts, Dr. Oglesby-Sherrouse works closely with the research groups of Drs. Wilks, Kane and Michel.
James Polli: Research in maximizing oral bioavailability through formulation and chemical approaches, and developing public quality standards for oral dosage forms. Dr Polli’s recent interests include metal-based drug speciation and pharmacokinetics through an FDA funded clinical trial. Dr. Polli is also co-director of the Center of Excellence in Regulatory Science and Innovation (CERSI).
C.S. Raman: Performs multifaceted structural and biological studies that combine high-resolution X-ray crystallography with biochemistry, biophysics, molecular biology, and evolutionary and phylogenetic analyses. Specific interests include syntrophy in polymicrobial systems as it pertains to energy, respiration and antibiotic resistance.
Jana Shen: Development of computational methods and tools for studying protein stability and folding; proton-coupled biological processes; pKa predictions; drug resistance; computational design of pH-sensitive drug carriers. Dr. Shen is co-director of CADD.
Yan Shu: Genetic mechanisms of drug response and the roles of membrane transporters in pharmacokinetics and clinical drug response. An emerging research interest is to understand the association between the exposure to the toxic metal cadmium in drug response and metabolic disorders.
Audra Stinchcomb: Transdermal prodrugs, microneedle-enhanced delivery, and translational research models for public-private partnerships. Her interests include understanding the role of the skin microbiome and the effects of metals (such as zinc) in influencing transdermal drug delivery.
Angela Wilks: Mechanistic understanding of heme uptake and utilization in bacterial pathogenesis through systems biology that combines bacterial genetics, metabolomics, biochemical and biophysical tools. Dr. Wilks works closely with Drs. Oglesby-Sherrouse and Kane on the heme and iron regulatory pathways, as well as Drs. MacKerell and Xue on antimicrobial drug development.
Patrick Wintrode: Characterization of pathological protein conformations using biophysical techniques such as mass spectrometry and computer simulations to elucidate how these contribute to protein function and disease. Dr. Wintrode has several collaborations with center members on metalloprotein structure function including Drs. Wilks and Michel.
Fengtian Xue: Rational design, synthesis, and biological evaluation of potential medicinal agents in the treatment of neurodegeneration, cancer and infectious disease. Dr. Xue collaborates with center members including Dr. Wilks and Dr. Hamza on the design of novel agents targeting heme uptake in bacterial and parasitic infections, respectively.
Richard Thompson: Development and application of fluorescence-based biosensors to address questions in biology, human health, and oceanography. Particular interests include the quantitative measurement and imaging zinc, copper, and other metal ions that are required nutrients in humans and other organisms.
David Weber: Structure and function of S100B a dimeric Calcium-binding protein that is overproduced during gliosis in patients with Alzheimer disease, Down syndrome, and Aids related dementia. In addition, S100B and/or other members of the S100 protein family are elevated in several cancers. Dr. Weber is the associate director of the Institute for Bioscience and Biotechnology (IBBR) and director of the University of Maryland Center for Biomolecular Therapeutics (CBT). He works closely with Dr. MacKerell and CADD on the development of S100B inhibitors.
Iqbal Hamza: Defining the cellular and molecular determinants of heme homeostasis in humans. Understanding how heme-iron is utilized will permit the development of novel nutritional strategies to ameliorate iron deficiency anemia in humans and uncover novel therapeutic drug targets against parasites.
Byung-Eun Kim: Defining the mechanisms of copper uptake, distribution, utilization, recycling, export and regulation at the cellular and molecular level in cell culture and animal models. Particular areas of focus are the role of copper in cardiovascular health and inter-organ copper signaling.
Gregory Duncan: Development of nanoscale measurement tools capable of shedding light on key processes in biology and medicine with an emphasis on pulmonary disease applications. Specifically, how biophysical and interfacial interactions between the mucus gel and periciliary layer on the lung airway surface impact mucus clearance in health and disease.
Aaron T. Smith: Structural, spectroscopic and enzymatic studies of the the heme-dependent aminoacyl-tRNA synthetase and aminoacyl tRNA transferases specific for arginine and their role in protein translation and post-translational modification. A second research area focuses on iron uptake via the ferrous iron uptake (Feo) system in bacterial pathogenesis.
Valeria Culotta: The study of metals at the host-pathogen interface. Metal ions such as Cu, Zn, Fe and Mn are essential nutrients for all living organisms and during infection, the host attempts to starve invading pathogens of these micronutrients through a process known as nutritional immunity. A major emphasis is on metals and SOD enzymes of the opportunistic fungal pathogen Candida albicans. The laboratory also investigates the unique metallobiology of the Lyme disease pathogen, Borrelia burgdorferi.
Svetlana Lutsenko: Research on the molecular mechanisms that regulate copper concentration in normal and diseased human cells. Copper is essential for human cell homeostasis and in embryonic development and neuronal function. Disruption of copper transport in human cells results in severe multi-system disorders such as Menkes disease and Wilson's disease.
Nicholas P. Farrell: Understanding of the role and utility of metal complexes in biology and medicine. Specifically, transition metal complexes as chemotherapeutic agents. Dr. Farrell developed the first non-cisplatin based analog BBR3464 to advance to Phase II clinical trials.