WENDELL S. AKERS, Ph.D. University of Kentucky College of Pharmacy
Faculty Position:	Assistant Professor, Clinical Specialist in Cardiology
Project Title:	“Role of Angiotensin II in Myocardial Ishcemia/Reperfusion Injury.”
Project Description:	Despite the well-documented benefits of bypass surgery in coronary artery disease, prolonged aortic cross-clamping during bypass surgery and myocardial reperfusion is associated with significant cardiac dysfunction. The purpose of this research proposal is to examine the role of the cardiac rennin-angiotensin system in the development of myocardial ischemia/reperfusion injury utilizing a perfused isolated rat heart model. The long-term goal of this research is to develop pharmacological interventions to attenuate the sequence of events that mediate extension of myocardial injury during myocardial ischemia/reperfusion.
CAROLYN L. BOUMA, Ph.D. Texas Tech University Health Sciences Center School of Pharmacy
Faculty Position:	Assistant Professor, Pharmaceutical Sciences
Project Title:	“Regulation of Maltose Metabolism in Fusobacterium Mortiferum.”
Project Description:	To develop a genetic analysis system for Fusobacterium species, which are Gram-negative, anaerobic human and animal pathogens. Because many members of this genus are resistant to antibiotics commonly used for selection in genetic systems, we have chosen to use a metabolic marker for selection. We have identified the maltose metabolic system of F.mortiferum as a candidate metabolic marker. Previous studies described the biochemistry of maltose metabolism in F.mortiferum. This proposal focuses on the regulation of maltose metabolism. We propose to (1) identify the promoter(s) of the mal operon, (2) construct an overproducing strain of the putative transcriptional regulator, and (3) assess the role of the transcriptional regulator in vivo and in vitro. Besides providing information on genetic regulation of the chosen selectable marker, this work will enhance basic knowledge of promoter structure and gene regulation in Gram-negative anaerobic organisms.
MARIA A. CROYLE, Ph.D. University of Texas at Austin College of Pharmacy
Faculty Position:	Assistant Professor, Pharmaceutics
Project Title:	“Effect of Polymer Size on the Pharmacokinetics, Biodistribution, and Immunogenicity of PEGylated Viral Vectors for Human Gene Therapy.”
Project Description:	Recently, a method for the rapid conjugation of functionalized PEG to free lysine groups on the adenoviral capsid has been established in our laboratories. This modification of viral vectors has reduced cellular and immune responses generated against viral capsid proteins. However, this effect was not absolute. In this project we plan to study the effect of PEG size on the pharmacological and immunological/toxicological profiles of first generation adenoviral vectors in immunocompetent animals.
CHRISTINE Y. HON, Pharm.D. Mercer University Southern School of Pharmacy
Faculty Position:	Assistant Professor, Pharmacy Administration
Project Title:	“Histamine Pharmacodynamics Among Healthy Caucasian Volunteers with Different Histamine N-methyltransferase Genotypes.”
Project Description:	Histamine is a mediator that plays an important role in the pathophysiology of allergic diseases such as asthma. It is metabolized by histamine N-methyltransferase (HNMT) and diamine oxidase. Wide variability of HNMT activity exists among individuals and reduced HNMT activity is caused by a C314T mutation in the gene. Corticosteroids are often used to treat diseases because of their anti-inflammatory effects. The pharmacodynamic effects of corticosteroids on whole blood histamine have been well described by the basophil trafficking model, whereas the effects on plasma histamine concentrations are less well defined. We hypothesize the HNMT genetic polymorphisms affect the pharmacodynamics of corticosteroids. Using pharmacodynamic modeling, we will characterize the changes of histamine concentrations upon corticosteroid administration in healthy Caucasian volunteers with different HNMT genotypes. This study will provide understanding of the mechanism responsible for the variable pharmacodynamic response to corticosteroids. It will lead to future development of strategies in dosage adjustments to reduce the variability of corticosteroid response. Individualization and optimization of corticosteroid therapy in patients with different inherited HNMT genetic characteristics will eventually be achieved.
ROSEMIN KASSAM, Ph.D. University of British Columbia Faculty of Pharmaceutical Sciences
Faculty Position:	Assistant Professor, Pharmacy Practice and Director of Structured Practice Education
Project Title:	“Informed Shared Decision Making (ISDM): A Model for Enhancing Student Learning in the Pharmacy Curriculum, Preceptor Curriculum and Pharmaceutical Care.”
Project Description:	There is a general acceptance among pharmacy practitioners that the development of a covenantal relationship is difficult and requires highly developed skills. Unfortunately, skills and competencies necessary to develop such a relationship have not been described in the literature and we are unaware of any training modules designed to facilitate this. The Informed Shared Decision Making (ISDM), a model for interpersonal communication developed by medicine, has the potential to enhance the pharmacist-patient relationship within the covenantal relationship model. The aim for this project is to adapt these competencies for pharmacy and develop a training module to facilitate this.
ROBERTA S. KING, Ph.D. University of Rhode Island College of Pharmacy
Faculty Position:	Assistant Professor, Medicinal Chemistry and Toxicology
Project Title:	“Sulfotransferase Inhibitors: Chemopreventative and Drug Interactions.”
Project Description:	The long-term goal of this study is to determine the structural features necessary for reversible inhibition of human sulfotransferase isoforms, especially that known as SUL1A1. The intent of this project is not to design the “best” inhibitor for sulfotransferases (for instance, for therapeutic use), but to understand what structural features contribute to inhibitory action so that potential interactions can be predicted. In vitro sulfotransferase assays will be used for this study. A collection of human liver cytosols will provide the enzyme source, commercially available p-nitrophenol will serve as selective substrate for SULT1A1 isoform, and enzyme activity in the absence and presence and of several concentrations of inhibitor will be measured utilizing an HPLC/UV analysis procedure. Data analysis includes determining the kinetic inhibition constants (Ki) by non-linear fitting of the data to the equations modeling reversible inhibition.
DAVID A. LATIF, Ph.D. Shenandoah University Bernard J. Dunn School of Pharmacy
Faculty Position:	Assistant Professor, Pharmacy Administration
Project Title:	“Ethical Reasoning in Pharmacy Students: A National Study.”
Project Description:	This investigation will have five objectives: (1) To measure the ethical reasoning of pharmacy students on a national basis; (2) To compare pharmacy students to normative baseline ethical reasoning scores of students in nursing and medicine; (3) To assess differences in ethical reasoning based on years of education and demographic factors; (4) To analyze the relationship between ethical reasoning, curricular and admissions structures; and (5) To suggest potential interventions designed to enhance ethical reasoning, regardless of how students score on ethical reasoning. Ethical (or moral) reasoning can be conceptually thought of as how to best organize social cooperation in society. Assessing ethical reasoning is important to the health professions because many studies suggest that high ethical reasoners rarely score low on measures of clinical performance. This preliminary study may lay the groundwork for subsequent studies that examine the relationship between ethical reasoning and educational interventions, as a criterion in the admissions process, and as a potential predictor of clinical decision making.
ANDREW L. LEE, Ph.D. University of North Carolina-Chapel Hill School of Pharmacy
Faculty Position:	Assistant Professor, Division of Medicinal Chemistry and Natural Products
Project Title:	“Structural Studies and Molecular Interactions of a BRCT Domain from Human DNA Polymerase µ.”
Project Description:	BRCT domains (BRCA1 C-terminal) are protein motifs approximately 95 amino acids in length that are found primarily in, though not limited to, DNA repair proteins. They are also found in proteins involved in other chromosomal events, such as recombination, transcription, checkpoint control, and chromatin remodeling. Although BRCT domains from various sources demonstrate different functions, in general they are viewed as molecular recognition motifs. Prompted by the limited amount of structural information currently available on these domains, and to gain insights into how these structurally similar domains reconcile their common features with functional diversity. NMR-based structure determination of the BRCT domain from human DNA polymerase Mu (pol µ) is proposed.
ROBERT L. PAGE II, Pharm.D. University of Colorado Health Sciences Center School of Pharmacy
Faculty Position:	Assistant Professor, Pharmacy Practice
Project Title:	“The Relationship Between Melatonin and Tumor Necrosis Factor-Alpha in Older Adults with Involuntary Weight Loss.”
Project Description:	Involuntary weight loss (IWL) in older adults has been associated with catastrophic health outcomes, such as functional decline, increased hospitalization and nursing home care, and death. Current pharmacotherapies for IWL are associated with severe side effects and are frequently poorly tolerated in the geriatric population. Research suggests that tumor necrosis factor-alpha (TNF) may play a role in cachexia and that the neurohormone melatonin (MLT) may participate in regulation of the immune system and cytokine production. Twenty-four adults = 70 years of age with IWL of = 5 pounds will be asked to participate in this investigation to determine: 1) if a relationship exists between endogenous MLT concentrations and circulating TNF concentrations and 2) if administration of exogenous oral MLT reduces TNF area under the curve. This study is intended to test the hypothesis that TNF concentration is inversely associated with endogenous MLT concentration in older adults with IWL. Furthermore, that the administration of exogenous oral MLT will decrease TNF exposure in these patients.
SAMUEL M. POLOYAC, Ph.D. University of Pittsburgh School of Pharmacy
Faculty Position:	Assistant Professor, Pharmaceutics
Project Title:	“Chemical and Neurotraumatic Alterations of Cytochrome P450 Mediated Arachidonic Acid Bioactivation in the Human Brain and CSF.”
Project Description:	Arachidonic acid metabolism to 20-HETE by cytochrome P450 enzymes is recognized as an important pathway of brain and kidney microvascular regulation. It is the purpose of this research to evaluate the production of this important vasoconstrictive mediator within the cerebrospinal fluid of brain-injured children. In addition, preliminary data by the principal investigator’s laboratory is the first evidence of in vitro 20-HETE production within human brain tissue. It is the purpose of the specific aims of this proposal to identify the cytochrome P450 isoform(s) involved in the formation of 20-HETE in the human brain and to identify chemicals which specifically inhibit 20-HETE formation in human brain tissue. The rationale for these studies is that our elucidation of the effect of chemical inhibition and neurotraumatic events on 20-HETE formation will allow for the potential future development of novel therapeutic strategies aimed at this pathway as a mechanism for the treatment of neurotraumatic disease.
SCOTT R. RAJSKI, Ph.D. University of Wisconsin-Madison School of Pharmacy
Faculty Position:	Assistant Professor, Pharmaceutical Sciences
Project Title:	“Development of Methyltransferase-Dependent DNA Modifying Agents.”
Project Description:	The primary objective of the disclosed research is to develop small molecules capable of highly selective DNA modifications of potential therapeutic significance. Importantly, these molecules will derive not only their specificity but also their reactivity from a DNA methyltransferase. This represents a new approach in obtaining specificity in small molecule DNA interactions by simple modification of the ubiquitous cofactor S-adenosylmethionine.
PAMALA J. REED, Pharm.D. University of Tennessee College of Pharmacy
Faculty Position:	Assistant Professor, Pharmacy Practice
Project Title:	“Impact of Negative Affectivity on Patient Reported Health Related Quality of Life.”
Project Description:	Negative affectivity (NA), a personality trait that reflects stable and pervasive differences in negative mood and self-concept, has been shown to be strongly and consistently correlated to patient reported, subjective health indicators. Therefore, subjective health indicators may or may not give an accurate assessment of the individual’s true health status. The pervasive influence of NA may confound the results and complicate the interpretation of health related quality of life instruments, such as the MOS SF-12 and SF-36. This project will include data collection using the SF-36 and the PANAS, a negative affectivity instrument, in a sample of patients utilizing a large family medicine practice. This data will be used to impact the NA on health status measures frequently used in pharmacoeconomic evaluations.
MICHAEL A. REPKA, Ph.D. University of Mississippi School of Pharmacy
Faculty Position:	Assistant Professor, Pharmaceutics
Project Title:	“Antifungal Denture Adhesive Film.”
Project Description:	The purpose of this research project is to incorporate two model antifungal drugs, nystatin and clotrimazole, into a bioadhesive, bio-erodable, polymer matrix to produce an “Antifungal Denture Adhesive Film”. The purpose of this film is two-fold: (1) The antifungal medicament is used for primary or adjunct treatment of fungal infections (e.g., candidiasis) of the oral mucosal. This is accomplished via the controlled release of the antifungal agent from the polymer matrix and (2) the bioadhesive matrix serves as a denture adhesive for the subject for use in the interim while the oral infection is being treated.
DAVID W. THOMAS, Ph.D. University of the Pacific Thomas J. Long School of Pharmacy and Allied Health
Faculty Position:	Assistant Professor, Biological Sciences
Project Title:	“The Role of the Ryanodine Receptor in T Cell Activation.”
Project Description:	The objective of this project is to test the hypothesis that the ryanodine receptors are essential protein mediators of T lymphocyte activation. The ryanodine receptors are proposed to control T cell activation via their actions to induce the sustained calcium signal needed for T cell growth. To test this idea, the main experimental approach adopted is to knock out ryanodine receptor gene expression using DNA antisense methods and investigate effects on calcium signaling dynamics, as well as fundamental parameters of cellular activation including the induction of cytokine gene expression.
CHARLES R. YATES, Ph.D. University of Tennessee College of Pharmacy
Faculty Position:	Assistant Professor, Department of Pharmaceutical Sciences
Project Title:	“Mechanism(s) Underlying Race-Specific Differences in Cyclosporine Pharmacokinetics.”
Project Description:	Renal allograft long-term survival is different among ethnic groups with African Americans having the poorest allograft survival prognosis. Differences in the pharmacokinetics of immunosuppressive drugs (e.g., cyclosporine) between Caucasians and African Americans have been described as contributing to ethnic differences in clinical outcomes. We hypothesize that ethnic differences in CYP3A5 genotype and expression contribute to race-specific differences in the pharmacokinetics of the immunosuppressive drug cyclosporine. NONMEM will be used to evaluate cyclosporine disposition in 21 (11 blacks and 10 whites) renal transplant patients previously receiving orally administered cyclosporine. PCR amplification of specific alleles (PASA) will be used to develop PCR-based genotyping assays for the detection of the CYP3A5 aberrant alleles CYP3A5*3 and CYP3A5*6. CYP3A5 genotype will be determined in study participants. CYP3A5 genotype, as well as other patient demographics (e.g., race), will be evaluated as covariates.
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