Potential Research Projects

Edward Bilsky, Ph.D.
Associate Professor, Department of Pharmacology

The research in my laboratory focuses on opioid pharmacology and its applications to the fields of pain management and addiction. Active projects are listed below. Many of these areas are ideal for undergraduate research projects and I have established a track record in offering meaningful research experiences to undergraduate students. I have had a total of 3 individual SURF fellowships over the past four summers, and all three recipients have presented their work at major scientific meetings (Experimental Biology, INRC, Society for Neuroscience, etc.) and/or have published in peer-reviewed journals.

My most recent fellow, John Lowery, presented his work at the Experimental Biology meeting in 2003. He is also a co-author on a paper that has been conditionally accepted to the Journal of Pharmacology and Experimental Therapeutics. Many of the other undergraduate students in my laboratory have also presented their work at national meetings and/or published with me as co-authors. One of my greatest accomplishments in the six years I have been directing a laboratory has been placing four of my students into Ph.D. programs in pharmacology or a related field of biomedical research. I have two other students who I foresee pursuing a Ph.D. degree in neuroscience or pharmacology within the next year.

In general, a student who begins working in my laboratory is paired with a more senior graduate student or technician in order to receive training in specific techniques. I also frequently work directly with the students in the laboratory. They are also expected to attend the weekly lab meetings, and I provide them with background readings on the projects that we are currently working on. As they gain experience, the students choose a project of interest and are given increasingly greater levels of responsibility. The student’s ability and dedication to the research in part determine how far they take a project. With motivated students who become part of the laboratory for a number of years, publications are the ultimate goal of the undergraduate research experience. They become involved in all aspects of the manuscript preparation process. For a student that is only available for the summer, the goal is to have them complete a project that can be presented at a national meeting.

Current Research Projects in the Bilsky Laboratory:

1. Role of basal signaling in the development and expression of opioid physical dependence and tolerance.
2. Development of nonpeptidic mu agonists/delta antagonists.
3. Structure-activity studies with opioid glycopeptides.
4. Role of dynorphin and catecholamines in memory and learning processes in aged and aged-stressed mice.
5. Genetic basis of inbred mouse phenotypes relevant to opioid addiction.

Amy J. Davidoff, Ph.D.
Associate Professor, Department of Pharmacology

The laboratory is currently engaged in defining the intracellular signaling pathways associated with the development of abnormal excitation-contraction (E-C) coupling associated with heart disease, with a particular emphasis on diabetic cardiomyopathy. Biophysical techniques are employed to evaluate E-C coupling in single ventricular myocytes (e.g., whole-cell current and voltage clamp techniques, and a video edge-detection system coupled with spectrofluorometry (fura-2 and fluo-4), and biochemical/molecular biological techniques to evaluate protein content and enzyme activities. Projects involving video edge-detection are highly suited for summer research projects involving undergraduate students. For those students who continue to work in the laboratory throughout the academic year, students are often trained in more than one technique (e.g., coupling biophysical and molecular techniques).

We are presently focusing on determining whether there are links between abnormal myocardial E-C coupling and insulin signaling. We utilize in vivo models of type 1 and type 2 diabetes, as well as, primary cell culture systems, to determine the pathogenesis of diabetic cardiomyopathy. Pharmacological manipulations of pathways associated with E-C coupling and insulin signaling are readily available (e.g., PKC isoform inhibition, PI-3 kinase inhibition, -adrenergic receptor subtype activation/inhibition). Ongoing projects include understanding the impact on expression and function of cellular Ca2+ regulation (e.g., L-type calcium channel, sarco/endoplasmic reticulum ATPase (SERCA), Na-Ca exchanger (NCX), ryanodine receptor (RYR) as they relate to:

- -adrenergic receptor signaling (receptor subtypes and PKA activity).
- Insulin signaling (with emphasis on PI3-kinase dependent pathways).
- N- and O-linked glycosylation.
- Glucose-induced PKC activation.

Dr. Davidoff has supervised nine undergraduate and six medical students in a variety of research projects since joining the faculty at the University of New England. Most of the undergraduate students were recipients of either an American Heart Association or American Physiological Society summer research fellowship, and have presented their work at national (e.g., Biophysical Society, Experimental Biology, International Society of Heart Research) or regional (e.g., New England Pharmacology) conferences.

David Johnson, Ph.D.
Associate Professor, Chair, Department of Physiology

Students will work with Dr. Johnson using reverse transcriptase/PCR techniques to quantify hippocampal levels of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). Neurotrophins have been indicated as potential therapeutics for brain trauma and Alzheimer’s dementia. Dr. Johnson has recently established collaborations with Drs. Novotny and Bilsky (both at the University of New England) involving PCR techniques and are routinely performing these assays. All of these procedures are amenable for undergraduate research. Dr. Johnson has supervised a number of students at the University of New England most of whom have presented at national scientific meetings (e.g., Society of Neuroscience) and regional meetings (e.g., New England Pharmacology).

Debra McDonough, Ph.D.
Assistant Professor, Department of Biological Sciences, College of Arts and Sciences

Dr. McDonough is a genomicist interested in applications of genomic data to biological questions. She is beginning a collaboration with Dr. Bilsky in which her lab will use QTL mapping to identify chromosomal regions that contain genes involved in morphine addiction. Dr. Bilsky has identified two inbred strains of mice that respond very differently to morphine. Approximately 300 F2 cross progeny of the inbred parental strains will be genotyped and tested individually for their response to morphine. Student research assistants interested in behavior can be involved in measuring the degree of locomotor activity induced by morphine in the experimental mice. Students more interested in the techniques of molecular biology can find a role in the genotyping end of the project.

As these students learn the relatively straightforward techniques of PCR and fluorescent fragment analysis, their work in the lab will become more and more independent. While the statistical analysis of correlations between the phenotypic and genotypic data are quite involved, students who have participated in the data generating phases of the project will be encouraged to participate in this phase of the project as well. We expect to complete the initial QTL analysis within two years, so a student could potentially be involved in this project start to finish. An AREA grant application to NIDA has just been submitted to help support the research and undergraduate involvement in it.

Additional projects in Dr. McDonough's lab include genetically tracking salmon in the local Saco River to better understand the population structure and an analysis of gene conversion events in the Myosin Heavy Chain gene cluster.

Ian Meng, Ph.D.
Associate Professor, Department of Physiology

Dr. Meng’s research focuses on the neurophysiological mechanisms underlying the suppression and facilitation of pain. Dr. Meng uses an integrative approach, relating behavior to the activity of single brain neurons in rodents. The brain can both inhibit and facilitate pain signals through projections to the spinal cord dorsal horn. Morphine and stress produce analgesia by activating a pain inhibitory pathway that includes the amygdala, periaqueductal gray region, and the rostral ventromedial medulla (RVM). Morphine tolerance and certain types of chronic pain involve the activation of a pain facilitating pathway that also includes a projection from the RVM to the spinal cord dorsal horn. Dr. Meng’s research examines how activation or inhibition of specific neuronal subtypes in the pain modulating pathway can lead to increases or decreases in pain. Students who work in the lab have the opportunity to learn experimental design and analysis, scientific writing skills, and several laboratory techniques used to carry out experiments. Procedures include small animal surgery, stereotaxic surgery for microinjection of drugs, single unit electrophysiology and behavioral pain tests.

David Mokler, Ph.D.
Professor, Department of Pharmacology

Projects that students can pursue involve investigating the actions of drugs of abuse on the interactions of neurotransmitter systems of the brain. Acute and chronic use of drugs of abuse alters the neurochemistry of the brain, changing the balance of serotonin and dopamine in structures of the forebrain. In vivo microdialysis is used to assess the impact of acute and chronic drug use on the release of dopamine and serotonin within the forebrain of conscious, behaving rats.

Within that context, students will be allowed to design and implement their own research projects. Dr. Mokler strongly encourages students to spend two years in his lab. This allows students to gain an initial background in the methods in the lab prior to a decision on a project that the student can pursue. Techniques, which the students use, include stereotaxic surgery, high performance liquid chromatography, in vivo microdialysis and histology. Students work together as a team with Dr. Mokler. Students are required to present research at a number of different venues, including University of New England Undergraduate Research Conference, New England Pharmacology, Experimental Biology and the Society for Neuroscience meetings.

Dr. Mokler has had over 30 undergraduate students who have worked in his laboratory at the University of New England. The majority of these students are in medical school, or have finished their medical training and are practicing physicians. Five students have gone on to graduate school in the health sciences or are employed in the health science field. Many have co-authored papers and presented their research at national meetings such as Society for Neuroscience and Experimental Biology.

Richard Reese, M.D.
Professor and Chair, Department of Pharmacology

My perspective as a clinician is significantly different from most of the rest of the basic science faculty at the University of New England. I offer students the chance to work with me on a pharmacology-related writing project for the State of Maine Bureau of Health that involves the "judicious use of antibiotics in the therapy of upper respiratory tract infections.” This is a state Bureau of Health Department concern and a priority, especially as it relates to decreasing the selection of resistant bacteria. The project is encouraged/endorsed by the Centers of Disease Control (CDC, Atlanta, GA). In fact had it not been for 9/11, issues relating to antibiotic resistance would have been one of the CDC's highest priorities.

I will be again preparing a couple of state-sponsored newsletters, evidence-based as much as possible, on specific related topics, and these are mailed as clinical education CME-like pieces to all primary care providers in the state of Maine. A student could gain valuable clinical experience helping me with these reports, and the project may progress to an evidence-based analysis that shapes state government policy. The student would help review the related clinical literature, attend state Bureau of Health related meetings with me (when possible), help write the drafts and final product with patient education sheets for 1-2 topics. Although this is not a lab experience, for a student it could be a unique opportunity to do a project best categorized as public health-infectious disease-related teaching project.

Barbara J. Winterson, Ph.D.
Professor, Department of Physiology

One research focus of our laboratory is the investigation of mechanisms of plasticity in the flexor reflex of the laboratory rat, in particular long-term changes in the reflex as a consequence of injurious stimulation. Currently, we are making precision measurements of hindlimb force with a computerized data acquisition system. The preparation is an anesthetized, spinalized rat and using pharmacological antagonist drugs to test the involvement of glutamate, tachykinins, and nitric oxide in the reduction or enhancement of brief and prolonged noxious percutaneous electrical stimulation. This animal model may shed light on the pathophysiological mechanisms underlying disordered motor function in clinical musculoskeletal problems such as low back pain.

Another area of research activity involves a collaboration with Dr. Geoffrey Bove, (Beth Israel Hospital, Harvard Medical School, Boston). We are investigating hindpaw hyperalgesia in neuropathic rats with a modified von Frey method. This research is designed to evaluate mechanisms underlying pain sensation as a consequence of nerve injury. Although these experiments require a significant amount of training, aspects are conducive for undergraduate research projects.

John P. Wise, Ph.D.
Adjunct Professor, Department of Pharmacology

Dr. John Wise is an adjunct professor of pharmacology at the University of New England. His primary appointment is at the University of Southern Maine where he heads the Center for Integrated and Applied Environmental Toxicology. Dr. Wise works closely with Drs. Bilsky and Davidoff at a number of levels including work on a recent grant submission to study heavy metal exposure and cardio- and behavioral-toxicity. The two campuses are in close proximity to each other and there are routine meetings between the two groups. His research focuses on the cytotoxicity and genotoxicity of particulate and soluble hexavalent chromium in human lung cells. He has agreed to serve as a potential mentor for any undergraduates interested in his research.

Students conducting summer internships in the Wise Laboratory of Environmental and Genetic Toxicology and the University of Southern Maine will have the opportunity to investigate the toxicology of metals in human, marine mammal, and fish cells particularly focusing on genotoxic, cell signaling and gene expression effects. Students will be trained in the culture and maintenance of fibroblast and epithelial cells and the exposure of these cells to metal toxicants. Experimental assays may include some or all of the following: establishing novel cell lines, growth curves, cytotoxicity assays, chromosome damage assays, mitotic index assays, cell cycle analysis, transfections, transformations, and/or single cell gel electrophoresis (comet assay). Molecular techniques may include Northern blots, Western blots, PCR, qPCR, and microarrays.
    
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