Reproductive Endocrinology; Apoptosis and cell death; Cell growth, differentiation and development; Endocrinology; Gene Expression; Molecular genetics; Signal Transduction; Toxicology and Xenobiotics; Vitamins and Trace Nutrient
My research focuses on developing, promoting, and evaluating effective means of pharmacology instruction at the undergraduate, graduate, professional, and interprofessional levels. Developing a competency-based curriculum in pharmacology for students at all levels, I have incorporated specific instructional methods into existing core courses that has in effect taken a sometimes intimidating subject like pharmacology and presented it to students in manageable way. Studies of the effectiveness of these methods are conducted in collaboration with the American Society of Pharmacology and Experimental Therapeutics (ASPET) and its Division of Pharmacology Education of which I am a recently appointed Fellow. Specific instructional methods in the study include: patient case presentations by dental students which utilize rubric descriptors of performance quality; Pharm Fridays with second year medical students incorporating organized lists of pertinent drugs to recognize, student-oriented learning objectives, pharmacology study guides, and active participation clicker sessions with relevant board-style pharmacology questions; development of performance-based pharmacology questions within the multidisciplinary objective structured clinical exam (OSCE) taken by all DDS candidates; and video clip presentations within classes demonstrating pertinent pharmacology topics such as medical sedation, use of emergency drugs in the clinic, and alternative means for pain management with interviews of clinical experts. These and other instructional methods in the study are highly rated by students and proven effective by outcomes on standardized exams.
Infectious Disease; Infectious Disease; Microbial Pathogenesis; Vitamins and Trace Nutrient
I care for patients who are hospitalized at Erie County Medical Center where I also serve as the hospital epidemiologist addressing infection control. I teach medical students, residents, and fellows in both hospital and classroom settings. In UB’s schools of medicine and dentistry, I teach a variety of topics including microbiology, pharmacology and toxicology, oral biology, and gastrointestinal systems, host defenses, and global health. I also conduct laboratory research on diarrhea-producing strains of E. coli bacteria. My lab focuses on enteropathogenic Escherichia coli (EPEC), Shiga-toxigenic E. coli (STEC, aka EHEC) and enterotoxigenic E. coli (ETEC). We are working on the role of intestinal host defenses such as nitric oxide and on the immune modulatory effects of adenosine. We have discovered that zinc can directly inhibit the virulence of pathogenic bacteria, and we are working on turning these laboratory findings into treatments. In our work on zinc we collaborate with Michael Duffey, PhD, in the Department of Physiology and Biophysics. Recently we have discovered that zinc can inhibit the development of resistance to antibiotics in Escherichia coli and other bacteria. Zinc does this by its ability to inhibit the SOS response, a bacterial stress response triggered by damage to the bacterial DNA. We are collaborating with Dr. Mark Sutton of Biochemistry to better determine the mechanism of zinc in this regard. I am interested in international medicine and global health and participate in an annual medical mission trip to Honduras, a trip in which student volunteers are encouraged to participate. Closer to home, I am a volunteer physician at Good Neighbors Health Center, a free clinic for the underserved on Jefferson Avenue in Buffalo. Resident physicians are encouraged to volunteer, and students may also be able to arrange clinical experiences. I am Co-Medical Director, with Dr. Ryosuke Osawa, of the Erie County TB Clinic. Learning experiences in my laboratory, in infection prevention and hospital epidemiology, or in international health, may be available for motivated students, residents, and fellows.
Protein Function and Structure; Proteins and metalloenzymes; Vitamins and Trace Nutrient
Cytochrome P450 enzymes are powerful catalysts that play integral roles in biochemical pathways throughout nature. In mammals, members of this class of enzyme serve a variety of functions that include drug metabolism, steroid biosynthesis and the activation and deactivation of vitamin D, to name a few. Cytochrome P450 enzymes are also heavily involved in bacterial and plant biochemistry. The overall goal of our research is to use a combination of biochemical and biophysical tools to investigate structure and function in class I cytochrome P450 enzymes, thereby contributing toward an understanding of how this important class of enzymes work as well as informing the design of therapeutics. This goal is divided between two efforts. First, we are interested in characterizing the substrate and redox partner interactions of the enzyme CYP24A1, the P450 responsible for deactivating vitamin D. Describing the interaction between CYP24A1 and vitamin D has the potential to illuminate how the vitamin D structure becomes modified at a particular site. This insight could impact the design of vitamin D analogs with benefits for an array of human health conditions, including bone density disorders, diabetes and chronic kidney disease (CKD). A parallel effort in our group is a structural study of the enzyme CYP121 of Mycobacterium tuberculosis, the disease-causing pathogen in tuberculosis (TB). The resurgence of standard TB and the rise of drug-resistant forms of TB are quickly becoming a global pandemic, with TB claiming more lives worldwide in 2014 than HIV. CYP121 is essential for survival of the bacterium and thus has emerged as one of the more promising antitubercular drug targets. Students and postdocs joining my lab will be exposed to a multidisciplinary set of research tools, including expression and purification of recombinant membrane protein, nuclear magnetic resonance, protein X-ray crystallography and P450 ligand binding assays.
Membrane Transport (Ion Transport); Neurobiology; Protein Function and Structure; Proteins and metalloenzymes; Vitamins and Trace Nutrient
The long term goal of the research conducted in my lab is to learn about the general principles that organisms use to acquire and metabolize the essential nutrients iron, manganese and copper. Since in eukaryotes, iron metabolism, for example, depends on the activity of copper-containing enzymes called ferroxidases, we examine the trafficking copper in cells as well. In addition, as divalent metal ions, manganese and ferrous iron share many of the same trafficking pathways. The first challenge for a cell is to scavenge these metals from the environment. This is true for a yeast cell in culture, for an epithelial cell in your intestine, an endothelial cell in the capillaries in the brain, or a neuron. The second challenge is to efficiently and correctly partition these metals in the cell for subsequent utilization and storage. Ultimately the cell or organism will have to regulate the accumulation of these metals and to ensure that they are not allowed to roam "free" since all three are toxic. Yet all are essential micronutrients, as well. They are required in fundamental cellular processes such as cellular respiration in all organisms, and for vital physiologic functions such as oxygen transport in blood and muscle. The brain has a strong requirement for iron and copper to support the elevated energy metabolism needed to support neuronal function; manganese is essential to neurotransmitter synthesis. This essentiality is contrasted by cytotoxicity that results from their strong tendency to generate oxygen radicals which in turn destroy key cellular components. For example, iron uptake into the brain must be tightly regulated, a process we focus in our research. Failure of this regulation can result in a variety of brain pathologies particularly those that result in degeneration of neuronal function. We study in detail the role of the amyloid precursor protein and alpha-synuclein in iron and manganese trafficking and how these functions are related these proteins‘ roles in neurodegenerative disease.
Cell growth, differentiation and development; Microbiology; Molecular Basis of Disease; Molecular and Cellular Biology; Regulation of metabolism; Signal Transduction; Toxicology and Xenobiotics; Vitamins and Trace Nutrient
Dr. Willsky’s research focuses on the role of oxovanadium compounds in cellular metabolism. V is a trace metal believed to be required for growth. Oral administration of oxovanadium compounds alleviates the symptoms of Diabetes in animal models and humans. The techniques of genetics, microbiology, molecular biology, biochemistry, pharmacology, magnetic resonance spectroscopy, and cell physiology are used. The diabetes-altered gene expression of genes involved in lipid metabolism, oxidative stress and signal transduction is returned to normal by V treatment of rats with STZ-induced diabetes, as demonstrated using DNA microarrays. Inhibition of tyrosine protein phosphatases is believed to be a major cause of the insulin-like effects of V. Our results implicate the interaction of V with cellular oxidation-reduction reactions as being important in the anti-diabetic mechanism of V complexes. A new project in the lab studies the mode of action of medicinal plant mixtures used by the native healers of Peru.