MSSRP Projects (2009) |
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Listed below is a subset of projects that were offered by preceptors for the 2009 Medical Student Summer Research Program, which is open only to rising second year UVA medical students. Check back in early 2010 for new project offerings.
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Faculty: W. Kline Bolton, MD
Department: Medicine/Nephrology
Phone: 4-5153
Title: Immunology of kidney disease
Abstract: Project in lab involves molecular dissection of the epitopes involved in Goodpasture's syndrome, the role of T regulatory cells in disease modification, and in chronic kidney disease (CKD). We use a rat model of Goodpasture's disease which can be induced with a single peptide which induces intra- and intermolecular epitope spreading on GBM antigens. Additional information:
http://www.healthsystem.virginia.edu/internet/researchfaculty/detail.cfm?people_id=wkb5s
http://www.healthsystem.virginia.edu/internet/researchfaculty/detail.cfm?people_id=jkg8h
Faculty: Bijoy K. Kundu, PhD
Department: Radiology
Phone: 4-0284
Title: Dynamic FDG-PET Imaging In-Vivo to Evaluate Glucose Metabolism in a Mouse Model of Myocardial Hypertrophy
Abstract: Myocardial hypertrophy is initially an adaptive response to stress, but soon becomes maladaptive with on-going stress and can lead to heart failure. During hypertrophy there is a shift in substrate utilization from fatty acid to glucose, however the metabolic mechanism is poorly understood. A compartmental modeling technique will be used to analyze images obtained dynamically within a given imaging session to obtain rates of myocardial glucose uptake and utilization. The quantification of these rates has been complicated by two important factors: a) limited spatial and temporal resolution of previous generation small animal PET scanners leading to partial volume effects (PVE) and b) the spill-over (SP) of radioactivity from the blood-pool (BP) to the myocardium at earlier time points and the spill-over from the myocardium to the BP at later time points thereby producing errors in the BP and myocardium tissue time activity curves. The BP time activity curves form the input for the compartmental model. This input function can be obtained either by direct arterial blood sampling or by measurement from PET images. This project will validate a method for obtaining an input function from dynamic image data, which accounts for the SP and PV effects, in a mouse model of pressure-overload LV hypertrophy, to obtain a model corrected input function (MCIF). The role of cardiac gating on MCIF will also be evaluated.
Faculty: Jim B. Tucker, MD
Department: Psychiatry and Neurobehavioral Sciences
Phone: 4-2281
Title: Children who claim to remember previous lives (Two students requested)
Abstract: Student will review case reports (including medical records, interviews, and correspondence) of children who claim to remember a previous life, with the aim of quantifying and entering the data in a codebook. Student will participate in a weekly research lunch focusing on the scientific study of unusual phenomena including near-death experiences and cases of the reincarnation type.
Faculty: Slobodan M. Todorovic, MD, PhD
Department: Anesthesiology
Phone: 3-9993
Title: T-type calcium channels in the action of anesthetics
Abstract: Previous data have indicated that T-type calcium channels (low-voltage activated, LVA, T-channels) are potently inhibited by volatile anesthetics. Although the interactions of T-channels with a number of anesthetics have been described, the mechanisms by which these agents modulate channel activity, and the functional consequences of such interactions, are not well studied. Recently, we used patch-clamp recordings to explore the actions of a prototypical volatile anesthetic, isoflurane, on recombinant human CaV3.1 and CaV3.2 isoforms. We also performed behavioral testing of anesthetic end-points in mice lacking CaV3.2 channels. Isoflurane applied at resting channel states blocked current through both isoforms in a similar manner at clinically relevant concentrations (1 minimum alveolar concentration, MAC). In behavioral tests, CaV3.2 knockout (KO) mice showed significantly decreased MAC in comparison to wild type (WT) littermates. KO and WT mice did not differ in loss of righting reflex (LORR), but mutant mice displayed a delayed onset of anesthetic induction. We conclude that state-dependent inhibition of T-channel isoforms in the central and peripheral nervous system may contribute to isoflurane's important clinical effects.
We plan to continue these studies by testing the effects of novel blockers of T-type calcium channels on anesthetic end-points in behavioral tests in wild type and knocout mice. It is hoped that these studies will contribute to development of better and safer clinical anesthetics.
Faculty: Diane Pappas, MD
Department: Pediatrics
Phone: 4-9130
Title: Medical care of vulnerable children (1 - 2 projects available)
Abstract: The project(s) may include:
Use of a brief, 4-question survey to screen for social disadvantage in children and their families and to assess the possible benefit of referral to social work. Project includes clinical shadowing.
Obstacles to providing care at UVA for vulnerable populations of children. Parents arriving at the clinic will be asked about obstacles to their children's receiving medical care such as transportation, cost, and language interpreters. Project includes clinical shadowing.
Partnering with the Health Department to identify important public health issues in the community, such as children's immunization rates or lead levels. Project includes clinical shadowing.
Faculty: Jeffrey Young, MD
Department: Surgery
Phone: 2-3549
(Three students requested)
Title: Decision making by resident physicians
Abstract: We will investigate the decision making of residents using the Critical Incident Method described by Gary Klein, PhD. The student will conduct interviews investigating incidents where the subjects made good, and bad decisions and try to elucidate the factors that lead residents of different levels of training to make either high quality, or low quality decisions under stress. We will use the results of this study to design educational programs and simulations that will allow residents to recognize when they are potentially making poor decisions, and to steer them toward high quality decisions.
Faculty: Peyton Taylor, MD
Department: Ob/Gyn
Phone: 4-9933
Title: Human Papillomavirus Genotyping in northern Tanzania
Abstract: This study will determine the genotypic distribution of Human papillomavirus (HPV) among women aged 18-55 in Northern Tanzania. Women will be recruited at Arusha Town Clinic in Arusha, Tanzania. Following an educational session, each woman will undergo an interview for sociodemographic information followed by a rapid HPV and complete gynecologic examination including Pap test and swab for HPVtesting. Magnification-directed biopsies will be performed on all women with visible cervical lesions at the time of the exam. All women found to have detectable cervical disease will be referred to Selian Gynecology for further evaluation and treatment. Data collected will provide information about the distribution of HPV genotypes in this unstudied patient population, critical information needed prior to initiation of widespread vaccine implementation strategies. Further, comparative analysis may provide information on the appropriateness of various screening tools in this unique population. Lastly, through participation in this study, women in this area will receive screening for cervical neoplasia which is too often not available to these women due to limited national resources for widespread screening programs. We plan to travel to Tanzania from July 1-30, 2009 with need for data support before and after the trip.
Faculty: Erik Gunderson, MD
Department: Psychiatry and Neurobehavioral Sciences
Phone: 3-0886
Title: The American Board of Internal Medicine certification examination: A missed opportunity to guide general medical education on substance abuse
Abstract: Substance use, the number one cause of preventable morbidity and mortality nationwide, is associated with tremendous personal and societal costs. Although primary care physicians are well positioned to screen and intervene, most are unprepared due to inadequate substance abuse education. The American Board of Internal Medicine (ABIM), through its certification exam, plays a major role guiding medical training. The exam blueprint devotes only 2% of its questions to substance abuse, a disproportionate emphasis compared to other chronic medical conditions. The current project will review internal medicine continuing medical education (CME) courses delivered by the the top 50 medical schools nationwide to examine ABIM exam influence on substance abuse and other curricular content (other content can be included based on student interest). The student will collect course brochures and extract data with the PI, utilizing Excel and SPSS (no experience necessary). Co-authorship with possible presentation at a national meeting. Flexible work hours. Depending on interests, the student will be able to spend time with the PI during treatment of opioid dependence at the UMA primary care clinic (1/2 day per week) and/or at the Clinical Pharmacological Research Unit (CPRU), a human behavioral psychopharmacology lab testing medications for substance abuse.
Faculty: Christopher P. Holstege, MD
Department: Emergency Medicine
Phone: 4-5185
Title: Cardioprotective effects of insulin through survival signaling in cardiac cells
Abstract: HDIT has been documented to improve hemodynamic parameters compared to conventional treatments for calcium channel blocker (CCB) toxicity in animal studies and in human case reports. Our preliminary studies in heart cells have demonstrated that representative drugs (nifedipine, verapamil and diltiazem) from each class of CCBs inhibit glucose uptake and phosphorylation of AKT at serine 473 (AKT-S473p). These observed effects were reversible in response to insulin treatment. The AKT-S473 phosphorylation site is key regulator of metabolic and inotropic responses during stress responses. Interestingly, nifedipine was the most potent inhibitor of glucose uptake, yet was nifedipine was most sensitive to the positive effects insulin on glucose uptake and AKT-S473p. Our data suggests nifedipine and verapamil may affect different signaling cascades downstream of AKT signal transduction. Our hypothesis is: High dose insulin as a treatment modality for calcium channel blocker toxicity provides cardioprotection during calcium channel blocker toxicity through inhibition of apoptotic effects, and improving excitation-contraction coupling in cardiac cells. The aims in this study are: (1) Characterize insulin's protective role during acute exposure to toxic levels of calcium channel blockers in cardiac cells; (2) Analyze the positive effects of insulin on activation of calcium-dependent sarcoplasmic reticulum receptors in response acute verapamil and nifedipine exposure in cardiac cells; (3) Study the effects of high dose insulin on AKT-dependent signaling mechanisms in aging cardiomyocytes exposed to acute calcium channel blocker toxicity. The results of this study will elucidate the role insulin has on activation of antiapoptotic cell survival mechanisms such as nitric oxide synthase regulation, and phospho-regulation of sarcoplasmic reticulum (SR) receptors (SR calcium-ATPase, SERCA; and ryanodine receptor, RyR2). Results will also determine if AKT-S473p is regulated differently in young, adult and elderly cardiomyocytes during insulin treatment of verapamil or nifedipine exposure. We propose to use three model systems for characterizing these effects: in vitro H9C2 rat cardiomyocytes; ex vivo rat cardiomyocytes; and in vivo whole-animal pig models. Each of these model systems will provide unique incite when monitoring the integrated signaling mechanisms contributing to insulin's protective effects during acute calcium channel blocker exposure.
Faculty: Benjamin P. Sneed, MD
Department: Medicine/General Medicine
Phone: 3 6361
Title: Reducing inappropriate antibiotic use for asymptomatic bacteriuria and minimizing catheter associated urinary tract infections via nurse/physician directed education and protocols
Abstract: Up to 25% of inpatients have an indwelling urinary catheter placed at some time during hospitalization. Catheter associated urinary tract infections (CAUTI) are the most common nosocomial infection (comprising up to 40% of hospital acquired infections) and are associated with increased cost and length of stay (LOS). Often, the distinction of asymptomatic bacteriuria from infection is difficult, and antibiotics are often used without differentiating the two. Inappropriate use of antibiotics is costly from a monetary standpoint, but it also increases the risk of development of antibiotic resistance. A reduction in both CAUTI and inappropriate antibiotic use can be achieved by three measures: physician and nurse education, protocols for the management of urinary catheters, and guidelines for the distinction of asymptomatic bacteriuria and catheter associated UTI that include criteria for the use of antibiotics.
Student will follow daily urinary catheter placement/duration/removal on general medicine floor to define pre-intervention epidemiology of catheter use and catheter associated urinary tract infections.
Faculty: Amir A. Jazaeri, MD
Department: Ob/Gyn
Phone: 3-9414
Title: Over-expression of EVI1 and prognosis of ovarian cancer
Abstract: In the United States 1.5% of all women will be diagnosed with epithelial ovarian cancer during their lifetime. Over 20,000 cases are diagnosed each year resulting in approximately 15,000 deaths. This makes epithelial ovarian cancer the fifth leading cause of cancer death in women and the most lethal of all gynecologic malignancies. After initial surgery and chemotherapy, more than 75% of patients relapse and eventually die of their disease, therefore a better understanding of ovarian cancer biology is needed in order to develop new and better treatments for this disease. In this project we propose investigating the role of the EVI1 gene, in ovarian cancer. Abnormally increased EVI1 levels are already known to be responsible for some forms of leukemia and correlate with poor prognosis in these patients. Our preliminary results show that EVI1 is present in much higher levels in ovarian cancer compared to normal ovarian tissue samples and therefore represents a good target for further investigation. Our hypothesis is that EVI1 over-expression promotes the growth and survival of ovarian cancer cells through de-regulation and inappropriate expression of downstream genes. The ideal student for this project is a person who already has had some lab experience (e.g. familiar with RT-PCR western blot, siRNA, or cell culture)
Faculty: Christopher Rembold, MD
Department: Medicine/Cardiovascular Medicine
Phone: 4-2825
Title: Cytoskeletal organization and force maintenace in swine carotid artery
Abstract: This project aims to identify the determinants of cytoskeletal reorganization in arterial smooth muscle contraction and characterize how they regulate the phenomenon of force potentiation, in which a prior submaximal contraction strengthens a subsequent contraction. The experimental design uses swine carotid arteries in a stimulus-induced contraction/relaxation protocol. The role of cytoskeletal organization will be delineated from that of simple crossbridge cycling. The latchbridge hypothesis sought to explain smooth muscle force maintenance even when the crossbridge phosphorylation falls. Although a growing body of suggests that activation-induced assembly of thin filaments is required for airway smooth muscle contraction, much less is known about the role of actin polymerization in arterial smooth muscle contraction. Our lab is among the forefront of groups researching an actin polymerization and cytoskeletal organization based mechanism of smooth muscle contraction. This mechanism should serve as an enhancement of the current latchbridge hypothesis of smooth muscle force maintenance.
Faculty: Donna Chen, MD, MPH
Department: Center for Biomedical Ethics and Humanities
Phone: 3-5804
Title: At our best in research ethics -- a project of appreciative inquiry
Abstract: Faculty at the Center for Biomedical Ethics and Humanities (Donna Chen, M.D., M.P.H. and Lois Shepherd, J.D.) are launching an Appreciative Inquiry project to define and share researchers' stories about when they have been at their best in managing ethical issues, concerns, or conflicts that have arisen in the course of their research. Following training in appreciative inquiry-based research approaches, the student research assistant in this position will gather recorded interviews with individuals involved in clinical research who have volunteered to talk about their experiences and to share their views about the attitudes, resources, systems, education, and collaborative efforts that they believe helped them be at their best in an ethically troublesome situation they resolved. The research assistant will also be involved in the early stages of analysis of the interviews conducted and planning for the dissemination and publication of the stories collected. Prior experience in social science research and/or qualitative research methods is desirable, but not required.
Faculty: Andrew Hoyer, MD
Department: Pediatrics & Radiology
Phone: 4-9119
Title: Pulmonary Hypertension in Extremely Low Birth Weight Infants
Abstract: Pulmonary hypertension can cause death in children and complicates many forms of congenital heart disease. The incidence and effects in ELBW infants are unknown. The student who undertakes this project will be exposed to neonatology, congenital heart disease, echocardiography, pulmonary hypertension, and data collection and analysis. The student will participate in the disign and conduct of a retrospective study to determine the incidence and degree of pulmonary hypertension in ELBW infants, and search the medical record to evaluate the outcome of infants with and without pulmonary hypertension. The goal is preparation of an abstract to be submitted to American College of Cardiology meeting or the Pediatric Academic Societies' meeting.
Faculty: Julie Haizlip, MD
Department: Pediatrics
Phone: 2-1707
Title: Relationships between health care providers and families of children dependent upon technology
Abstract: We are interviewing the families of children who are technology-dependent in daily life (those who require home ventilators, feeding tubes, home IV therapy, etc) to determine the characteristics of their successful relationships with health care professionals. The student participating in this project will be coached on the interviewing technique and then will be put into contact with appropriate families to interview through referrals from Pediatric physicians. These semi-structured nterviews will contain some elements of Appreciative Inquiry but also include more direct data gathering as well. Interviews will be conducted in conjunction with the families clinic appointments when possible. Some local travel may be required if a family requests that the interview be done at their home or another location. Ideally, the student will also be involved in the content analysis of the stories following data collection.
Faculty: Mark D. Okusa, MD
Department: Medicine/Nephrology
Phone: 4-1156
Title: Kidney injury and repair (student can choose among these projects)
Abstract:
1. Early innate response to ischemia-reperfusion injury (IRI). In these studies, we are exsamining the role of the mechanism of early activation of macrophages/dendritic cells leading to activation of natural killer T cells in renal IRI. These studies evaluate the efficacy and mechanism by which adenosine 2A agonists and sphingosine 1 phosphage analogs block this process. These compounds are in human clinical trials; thus, rapid translation to acute kidney injury is feasible.
2. Kidney regeneration following IRI. In this study, we are examining the role of adaptive immunity in the regenerative phase of IRI. Following IRI, activation of dendritic cells leads to an adaptive immune response by activating T lymphocytes in injury and repair. We are pursuing studies that dissect this pathway by studying the roles of macrophages and dendritic cells.
3. Novel treatment of diabetic nephropathy. We have an ongoing study examining the machinsms of inflammation in diabetic nephropathy and treatment with adenosine 2a agonists.
Faculty: Patricia Foley
Department: Office of VP for Research
Phone: 924-1884
Title: Development of a Novel injectable controlled anagesic delivery system for effective pain management
Abstract: The development of prolonged regional anethesia/analgesia could lead to the development of the next generation pain management therapies which significantly improves patient comfort and decreases nursing time. This study investigates the feasability of developing a suitable injectable carrier vehicle (polymer microspheres) for a widely used local anesthetic, ropivacaine, for drug delivery at the site of action over a prolonged period of time. This slow release formulation of ropivacaine would provide a long lasting analgesia without the adverse effects of systemic pain medications such as opiates and non-steriodal anti-inflammatory agents. Objectives include optimizing polymer characteristics, drug loading and release, injectility, and in vivo efficacy.
Faculty: Peter Ham
Department: Family Medicine
Phone: 243-4660
Title: Why Family Doctors Teach: Appreciative Inquiry Discovery
Abstract: Appreciative Inquire offers the chance to find out what part of your program is working well. Recognizing and encouraging positive behavior may be more effective than troubleshooting. The Family Medicine clerkship is an highly rated experience for students; yet, recruitment of doctors to mentor students is challenging. Students working on this project will interview family doctors who teach students and ask them for positive stories about teaching. This information will change orientation, teacher recruitment, and clerkship outreach materials.
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Projects that have matched and are no longer available:
Faculty: Fern R. Hauck, M.D., M.S.
Department: Emergency Medicine
Phone: 4-1632
Title: International Family Medicine Clinic
Abstract: The research project will be based in the International Family Medicine Clinic (IFMC) in the Department of Family Medicine. This clinic provides comprehensive, patient-centered care to refugees of all ages who originate from numerous countries and speak many languages. The student will participate in 1 clinic session per week (if desired) and complete a project that involving IFMC's patient population, such as a quality improvement or patient education project, analysis of data from the IFMC database, or others. Some of the time will be spent in independent study about issues relevant to the project, such as cultural competency, health screening of new refugees, etc. The student will meet regularly with Dr. Hauck to orient the student, allow the student to reflect on his or her experience, and to teach about specific issues. Foreign language proficiency is not required but an asset, as well as prior experience with immigrants/refugees.
Faculty: W. Michael Scheld, MD
Department: Internal Medicine/Infectious Diseases
Phone: 4-5991
Title: Late Stage Anthrax Therapies
Abstract: Bacillus anthracis is the causative agent of anthrax, a large gram positive bacillus, that produces three exotoxins: protective antigen (PA), edema factor (EF), and lethal factor (LF). The combination of PA plus EF forms edema toxin (EdTx), while the combination of PA and LF forms lethal toxin (LeTx). LeTx, is lethal alone for many species including mice, rabbits, and non-human primates. EdTx, it has been found recently, has also been found lethal for many species as well. Nevertheless, anthrax is characterized by a systemic infection with high-grade bacteremia, as well as toxin release. For these reasons, we have been studying the interaction between cell wall components and the toxins in various in vitro and in vivo systems.
We have also characterized a model of lethal anthrax infection following injection of live Bacillus anthracis vegetative bacilli. We have used a derivative of a Sterne strain for these experiments. We have also characterized a live anthrax model with another more attenuated strain of anthrax. The derivative of the Sterne strain produces all three exotoxins but is unencapsulated, and is therefore a BSL/2 pathogen which we can work with in the laboratory. Following challenge with live B anthracis vegetative bacilli, 100% of mice are dead in a few days. Ciprofloxacin, a relevant antimicrobial agent for the treatment of anthrax, does not rescue mice but ciprofloxacin plus adenosine A2a agonists significantly improve survival. We believe these results will improve with further testing.
Faculty: Coleen McNamara, MD
Department: Medicine/Cardiovascular Medicine
Phone: 3-9396
Title: Id3 Regulation of Adiponectin Expression
Abstract: Atherosclerosis is a progressive disease characterized by the accumulation of lipids, subsequent macrophage infiltration and changes in vascular smooth muscle cells that leads to the formation of fibrous plaques that may occlude blood vessels. Coordinated gene expression is essential to maintain normal vascular tissue structure and function and many transcription factors regulate these processes. One factor, Id3, is a basic helix-loop-helix (bHLH) transcription factor that has been shown to play a role in the growth and differentiation of a variety of cell types including smooth muscle cells and adipocytes. Id3 lacks the basic domain required for DNA binding, but can form heterodimers with other transcription factors known as E proteins and thereby inhibit gene transcription. Because of this mechanism of action, Id3 is considered a dominant negative inhibitor of DNA binding and transcription. Our lab is currently investigating the role of Id3 on the development of atherosclerosis and adipocyte differentiation and function. The research projects in the laboratory are currently focused on 1) understanding the mechanisms whereby Id3 regulates B lymphocyte homing and inflammatory responses in vascular tissue 2) how Id3 influences matrix proteins involved in plaque formation and 3) how Id3 regulates expression of adipocyte markers required for fat cell formation and function. The results obtained from these projects will identify key regulatory roles for Id3 in vascular disease and fat cell biology that may lead to the development of therapeutic treatment of atherosclerosis and obesity.
Faculty: Craig S. Nunemaker, PhD
Department: Medicine/Endocrinology
Phone: 4-0229
Title: Asseessing pancreatic islets for effects of diabetes
Abstract: Diabetes is a devastating metabolic disorder that affects more than 20 million people in the U.S. Diabetes is characterized by insulin resistance and declining insulin production, resulting in hyperglycemia and numerous secondary complications including cardiovascular disease, blindness, kidney failure, and death. A key element in the progression of diabetes is the destruction of insulin-producing cells in pancreatic islets called beta cells, w hich can result from chronic exposure to inflammatory mediators such as cytokines, reactive oxygen species, and lipid factors. For this project, students will learn to use fluorescence microscopy techniques to examine putative mouse models of diabetes for defects at the level of the pancreatic islet. Specifically, students will assess islet healh and function by the following endpoints: (a) glucose-stimulated insulin secretion (GSIS), (b) glucose-stimulated calcium flux (GSCa), (c) cell death, and (d) islet metabolism measured by mitochondrial activity.
Faculty: Susan C. Modesitt, MD
Department: Ob/Gyn
Phone: 4-5197
Title: Predicting the risk of endometrial cancer in obese women
Abstract: Obesity in the United States is reaching epic proportions as 65% of the populat ion is overweight (BMI≥25) and 30% are obese (BMI≥30). Obesity is linked to cancers of the colon, prostate, pancreas, breast and endometrium (uterine lining). Endometrial cancer is the 4th most common cancer in women in the US and is expected to affect 40,000 women in 2008. Recent data have shown that 40% of endometrial cancer may be attributed to obesity and this is thought to be primarily due to the increased estrogen production in adipocytes through the conversion of androgens to estrone. Yet not all obese women will develop endometrial cancer suggesting that other factors aside from the increased estrogen must also play a role in the process of malignant transformation. Protective factors in obese women include physical activity but the exact mechanisms that underlie such protection remain poorly understood.
The specific aims of this research project are to enroll postmenopausal overweight and obese women with and without endometrial cancer who are undergoing hysterectomy to prospectively define the biomedical parameters (including exercise ability) of these women and to collect fat and endometrial tissue at surgery to assess differences in adipocyte derived marker activity and correlate with outcomes. A second related project will be to survey obese women undergoing evaluation for bariatric surgery and collect blood and endometrial samples at the time of bariatric surgery.
Faculty: Mark J Jameson, MD, PhD
Department: Otolaryngology - Head and Neck Surgery
Phone: 4-2040
Title: Role of Insulin-like Growth Factor-l Receptor in Resistance to Anti-Epidermal Growth Factor Therapy in Head and Neck Squamous Cell Carcinoma
Abstract: Although overexpression of the epidermal growth factor receptor (EGFR) has been shown to be important in the growth of most head and neck squamous cell carcinomas (HNSCC), therapeutic agents that inhibit the EGFR have shown poor clinical efficacy. Our lab has previously shown that activation of the insulin-like growth factor-l receptor (IGF1R) can confer resistance to an EGFR antagonist in vitro. Our current studies are aimed at understanding the intracellular signaling mechanism by which this resistance develops and its potential clinical significance. Techniques used in the lab include tissue culture, colorimetric proliferation assays, flow cytometry-based cell cycle and apoptosis assessment, protein isolation, Western immunoblotting, molecular biology, ex vivo chemosensitivity assays, and xenograft tumor studies in nude mice. There will also be opportunities to observe tissue harvests and review treatment outcome-related data from patient records.
Faculty: Spencer C. Payne, MD
Department: Otolaryngology - Head & Neck Surgery
Phone: 4-5934
Title: Presence of B-cell receptor excision circles in the nasal cavities of rhinitis patients
Abstract: It is our hypothesis that current in vivo and in vitro allergy testing greatly overstates the presence of an allergic etiology for rhinitis possibly reducing the positive predictive value to as little as 50%. It is further our hypothesis that this error in diagnosis is not unidirectional and that many patients currently labeled as having non-allergic rhinitis might, in contrast, be suffering from allergic rhinitis. As B-cells mature and differentiate, they undergo isotype class switching. Specifically, the DNA within those cells eventually responsible for IgE production will undergo a process that results in the formation of B-cell receptor excision circles which can be detected through PCR. As such, its possible that the use of IgE B-cell receptor exicision circle (ε-BREC) isolation might better characterize the mechanism of a patients rhinitic symptoms. As part of this study, we also wish to determine the optimal method for sample collection and how this might correlate with other factors. The student researcher will be involved in the collection of specimen through patient interaction and then isolation and amplification of DNA from the samples to determine the presence of of BRECs. Familiarity with laboratory equipment and methods is recommended but not a requirement.
Faculty: P. Preston Reynolds, MD, PhD
Department: Medicine/General Medicine,Geriatrics & Palliative Care
Phone: 2-4227
Title: Enhancing Culturally Competent Care of Vulnerable Populations: Global Health in Your Own Back Yard
Abstract: This project will focus on researching the contributions of minority physicians to 1) advancing public health as a strategy to eliminating health disparities or 2) to the field of global public health. Depending on the student's interests and skills, this project will focus on archival and print materials or on-line and web-based materials. If possible, the student will be instructed on how to conduct an oral history and provided the opportunity to interview a leading minority physician on his or her area of research and work in medicine and public health.
Faculty: Mark D. Miller, MD
Department: Orthopaedic Surgery
Phone: 2-4832
Title: Biomechanical Testing of Edobutton CL and Endobutton Direct used in ACL reconstructions
Abstract: This is a biomechanical study comparing ultimate strength of 2 different fixation devices used in ACL reconstruction. This study involves Anterior cruciate ligament reconstructions in matched cadaver specimens. The use of CT scans to characterize tunnel volumes, intra-articular tunnel apertures and graft biomechanics using a MTS machine.
Faculty: Patricia Foley, DVM
Department: Office of VP for Research
Phone: 4-1884
Title: Development of a novel injectable controlled analgesic delivery system for effective pain management
Abstract: The development of prolonged regional anesthesia/analgesia could lead to the development of the next generation pain management therapies which significantly improves patient comfort and decreases nursing time. This study investigates the feasibility of developing a suitable injectable carrier vehicle (polymer microspheres) for a widely used local anesthetic, ropivacaine, for drug delivery at the site of action over a prolonged period of time. This slow release formulation of ropivacaine would provide long lasting analgesia without the adverse effects of systemic pain medications such as opiates and non-steroidal anti-inflammatory agents. Objectives include optimizing polymer characteristics, drug loading and release, injectability, and in vivo efficacy.
Department: Radiology
Phone: 4-9820
Title: Radiology in M1 Gross Anatomy: Improving the Effectiveness of Web-based Instruction
Abstract: We have previously developed a course involving imaging corellation with gross anatomy. We would like to continue to improve this course. A comprehensive survey at the end of the course has provided feedback to guide the further development. This will require adding cases and improving case quizzes as already developed. Skills relevant to web development would be very helpful but not absolutely necessary. The student will also learn image manipulation skills using Photoshop and use of our PACS system.
Faculty: David R. Diduch, MD
Department: Orthopaedic Surgery
Phone: 3-0274
Title: Clinical follow up following Bankart Repair
Abstract: This is a clinical study where we will be studying clinical outcomes in patients who have had a shoulder surgery following a bankart injury. This includes a physical exam and the use of validated patient reported outcomes instruments. A concurrent study is evaluating absorption of the anchors used to perform the repair using CT and MRI scanning.
Faculty: Christopher M. Kramer MD
Department: Radiology
Phone: 3-0736
Title: Comprehensive Magnetic Resonance in Peripheral Arterial Disease
Abstract: Over the past 6 years, our multi-disciplinary team of investigators have developed new MRI-based methods for clinical trials in peripheral arterial disease (PAD) to measure benefits of novel therapeutic approaches. These include imaging of atherosclerotic plaque volume and characteristics in the superficial femoral artery and measuring perfusion and metabolism in calf muscle at peak exercise in patients with PAD. We have embarked on a trial of lipid lowering with simvastatin, ezetimibe, or the combination of the two in PAD patients to assess all of the above endpoints. Patients are imaged at baseline and after beginning lipid-lowering therapy, they are imaged again yearly over 2 years. Approximately half of the patients have now returned after 2 yeasr of therapy and intensive data analysis is ongoing. MSSRP students would participate in the imaging studies and data analysis.
Faculty: William Brady, MD
Department: Emergency Medicine
Phone: 4-8485
Title: Predicting outcomes of cardiovascular illness by electrocardiogram QT interval (Two students requested)
Abstract: The QT interval represents the period of repolarization in the cardiac electrical P-QRS-T cycle. Prolongation of the QT interval is associated with clinical illness, including polymorphic ventricular tachycardia. The identification of a prolonged QT interval is not difficult for the clinician. Yet, the identification of meaningful QT interval prolongation is difficult -- i.e., little information exists as to what constitutes a clinically significant QT interval prolongation. The students will work with two emergency medicine faculty members (emergency medicine and toxicology) in the review of ECGs with prolongation of the QT interval and determination of ultimate patient outcome, thus providing some guidance to the clinician in the interpretation and risk stratification of such electrocardiograms.
Faculty: Martha Hellems, MD
Department: Pediatrics
Phone: 4-9130
Title: Global pediatrics
Abstract: Projects(s) may include:
Retrospective review of UVA experience with international adoption (e.g., correlation of histories of vaccination with measured antibody titers; results of screening for parasites, elevated lead levels and tuberculosis; survey of parents after adoption to assess "lessons learned." Project will utilize special database from International Adoption Clinic and will include clinical shadowing at that clinic.
Retrospective review of UVA experience in treating patients with "tropical" diseases such as malaria and dengue. This project will utilize the Clinical Data Repository (and other sources as needed) and will include clinical shadowing at the UVA Traveler's Clinic.
Faculty: Brian R. Wamhoff, PhD
Department: Medicine/Cardiovascular Medicine
Phone: 3-6525
Title: Sphingosine Kinase Activity Plays a Critical Role in Smooth Muscle Cell Phenotypic Modulation
Abstract: The plasma lysophospholipid mediator sphingosine-1-phosphate (S1P) is produced by sphingosine kinases 1 and 2 (Sphk1/Sphk2). We and others have shown that S1P signaling through three G-protein-coupled receptors (S1P1, S1P2, S1P3) plays a critical role in regulating vascular smooth muscle cell (SMC) phenotype following acute injury in vivo. The purpose of this study was to determine the role of sphingosine kinase activity in S1P-mediated SMC phenotypic modulation. For this MSSRP, the student will employ the mouse carotid artery injury technique in Sphk1 null mice to determine the role of Sphk1 in acute vascular injury. Similar studies will also be performed in wild type mice using novel Sphk1/Sphk2 inhibtors delevoped by our labs at UVa. The student will also learn and use fundemental molecular biology techniques to determine changes in gene and protein expression in these animals. Our data suggest that Sphk activity plays a critical role in SMC phenotypic modulation and that pharmacological modulation of S1P signaling by targeting Sphk1 may serve to attenuate vascular pathologies such as in-stent restenosis.
Faculty: Jason Lyman, MD, MS
Department: Public Health Sciences
Phone: 4-8240
Title: Developing a web-based resident profiling tool to support learning in practice-based learning and improvement
Abstract: We are developing web-based tools for UVa physicians (internists and pediatricians) to use to assess their practice styles and identify potential areas for quality improvement. There are several aspects to this project that a student could participate in and make valuable contributions. One role would be to help conduct data validation for the quality measures that we include. Such tools require readily available electronic data, but the accuracy of that information is often unknown. In order to determine which quality measures are most useful and accurate, we will be conducting a variety of retrospective chart reviews to assess data quality. A student who works on this project will gain a unique and valuable perspective on several issues related to the re-use of patient data for quality assessment and other needs. He/she will potentially help in the development of chart abstraction tools, conduct chart reviews (electronic and paper), perform some data entry and assist with data analysis. Secondly, we will be conducting evaluations of this system this summer, and a student could help design, conduct, and analyze the results from this evaluation.
Faculty: Eric Houpt MD
Department: Medicine/Infectious Diseases
Phone: 3-9326
Title: Development of PCR diagnostic tools to detect infectious diseases
Abstract: The Houpt laboratory has several projects involving development of quantitative PCR based diagnostics for infectious diseases, especially enterics and tuberculosis. The student will train in these techniques and develop a research project that incorporates one or more of the following areas: endpoint PCR with gel electrophoresis, real time PCR, real time PCR chemistries from SYBR green to internal probes, multiplex PCR, and multiplex probe detection with Luminex. The student will leave with a clear grasp of these molecular diagnostic technoloqies which can stay with the student forever and can be utilized for subsequent clinical investigation.
Faculty: John Kattwinkel, MD
Department: Pediatrics
Phone: 4-5428
Second slot added 3/31/09
Title: Comparison of clinical and electronic recordings of apnea in the NICU
Abstract: Over 50% of very low birthweight babies will have pathologic apnea, defined as lasting > 15 seconds and accompanied by bradycardia and/or oxygen desaturation. Undetected apnea of prematurity can be lethal and yet can appear without warning in an otherwise healthy infant. Past attempts to predict when babies will be sufficiently mature to be at low risk for having apnea have been based on beside nursing observations, which are believed to be highly unreflective of the true incidence of apnea.
We have recently networked all of the UVa NICU bedside monitors and are in the process of storing continuous waveforms of heartrate, impedence pneumography, and oximetry for all babies in the NICU since March, 2009. Computer programs are now being developed to analyze these waveforms to identify, catalogue, and characterize pathologic apnea events for subsequent development of an apnea risk score. This subproject will involve reviewing on-line and written patient bedside records to corelate nursing descriptions of apnea events with those identified by the electronic monitor record compiled by the computer. The findings will help to define the clinical importance of further developing the computerized apnea resource, will contribute to our knowledge of the relative importance of various waveform patterns leading to life-threatening events, and will also provide a baseline assessment of the accuracy of the bedside apnea record for future quality improvement initiatives.
Faculty: Wendy J Lynch, PhD
Department: Psychiatry and Neurobehavioral Sciences
Phone: 3-0580
Title: Signaling pathways in cocaine reinforcement
Abstract: While considerable evidence from studies with male animals implicates mesolimbic dopamine (DA) pathways in mediating cocaine reinforcement, particularly following short access (ShA) self-administration, it is becoming apparent that other mechanisms are involved in cocaine reinforcement followinq extended access (ExA) self-administration. Specifically, in addition to DA, it has been proposed that dysregulated glutamatergic signaling may be differentially involved in modulating cocaine reinforcement and reinstatement and that its role may become progressively more prominent with the level of exposure. Although there is evidence demonstrating sex and ovarian hormone modulation of cortico-mesolimbic DAergic signaling following ShA exposure, very little information is available on sex differences in DAergic signaling followlnq ExA exposure or on sex differences in glutamatergic signaling followinq either ShA or ExA cocaine exposure. Thus, in this project we will test the hypothesis that the DAergic and glutamatergic processes that mediate cocaine reinforcement vary as a function of sex, hormones, and stage of addiction.
Faculty: Michele Sale, PhD and Bradford B. Worrall, MD, MSc
Department: Medicine/Cardiovascular Medicine, Neurology
Phone: 4-2783 (Dr. Worrall's number)
(One or two students requested)
Title: Homocysteine, vitamin therapy, and stroke risk - Can genetic factors help solve this puzzle?
Abstract: Although elevated levels of homocysteine have been consistently associated with increased vascular risk, controversy remains as to the benefit, if any, of B vitamin therapy in reducing that risk. The Vitamin Intervention in Stroke Prevention trial was a large, multicenter treatment trial looking at high vs. low dose B vitamin therapy that found no benefit from vitamin therapy despite lowering of homocystein levels. Questions remain as to the impact of genetic factors on modifying risk or response to therapy. Analysis of candidate genes found a bimodal effect for variants of the TCN2 gene suggesting that one genotype may lower and one elevate risk in the setting of vitamin therapy. The current project will entail finer mapping of the TCN2 gene looking at treatment by dose effect in preventing recurrent stroke. The student will be responsible for planning the experimental design with the help of Drs. Sale and Worrall, conduct the PCR experiments, and participating in the analysis of results. The intended goal of the project will be submission of an abstract for the International Stroke Conference (February 2010 in San Antonio). In addition to the bench work, the student may participate in a phenotyping project that will allow subtype specific analysis in this and subsequent projects.
Faculty: Cirle A. Warren, MD
Department: Medicine/Infectious Disease
Phone: 4-9676
Title: Clostridium difficile infection in aged, malnourished mice
Abstract: This research aims to gain insight into why the elderly are more susceptible to the acquisition of, severe illness and high mortality from C. difficile. Mice, at least 10 months old, will be subjected to a protein-malnourishing protocol, pre-treated with antibiotics and infected with either toxigenic and non-toxigenic standard strains of C. difficile. The mice will be monitored for weight changes, clinical scores, diarrhea and degree of infection. Intestinal tissues will be harvested and processed for histologic scoring, cytokine changes and quantification of infection. Another set of young mice, about 8 weeks old, will be studied for comparison. The relationship of age, nutritional status and susceptibility to severe C. difficile infection will be assessed in this murine model.
Faculty: Irvinig Kron, MD
Department: Surgery
Phone: 4-9297
Titles/abstracts (one student can choose from two projects):
Expression of Growth Factors in Association with Compensatory Lung Growth. Our lab has shown that compensatory lung growth is receptive to exogenous growth factors which can significantly augment growth. Our current attention is focused on angiogenesis and vascular remodeling in compensatory lung growth, and we have recently shown that pneumonectomy induces vascular remodeling and arterial growth in the lungs of adult rats, which is proportionate to the number of lobes removed. Identification of the molecular mediators in compensatory lung growth could eventually permit the advancement of future therapies for lung injury, pulmonary hypertension, and lung transplantation.
The neurologic effects of cardio pulmonary bypass. Cardiac bypass surgery results in long-term cognitive deficits in a large percentage of the patients who undergo this life saving procedure. A clear understanding of the mechanisms underlying such deficits could lead to the development of rational therapeutic strategies to limit neurological damage associated with bypass surgery. We propose to characterize cognitive decline in a rat model of cardiopulmonary bypass (CPB), and apply this knowledge to evaluate mechanisms of, and therapies for, CPB-related injury.
Faculty: Victor Laubach, PhD
Department: Surgery
Phone: 4-9297
Title: Amelioration of Lung Ischemia-Reperfusion Injury
Abstract: Lung ischemia-reperfusion (IR) injury is a major complication after transplantation leading to higher post-operative mortality and late complications including chronic rejection. Our laboratory has established that early, acute lung IR injury is dependent on alveolar macrophage activation and TNF-alpha induction. One major anti-inflammatory mechanism in IR is mediated through the release of adenosine, and we have showed that activation of the A2A adenosine receptor (AR) reduces lung IR injury. Little is known about the role of other ARs in lung IR injury. Thus Aim 1 will determine the role of each AR in a mouse model of acute lung IR. Aim 2 will establish that A2AARs specifically on alveolar macrophages confer protection from acute lung IR injury. Aim 3 will determine if mechanisms of A2AAR attenuation of IR injury involve MAPK, NF-kB, and apoptosis pathways in macrophages. Our overall hypothesis is that specific activation of A2AARs on alveolar macrophages provides protection from post-transplant acute lung IR injury.
Faculty: J. Terry Saunders, PhD
Department: Medicine/Endocrinology
Phone: 4-0239
Title: Development of educational interventions for the training of residents in the management of diabetes
Abstract: The present research is a pilot study of an educational intervention for training general medicine residents in three specific diabetes care skill sets during their rotation through the endocrinology and diabetes clinics. Well-trained simulated patients (SP's) portray cases focusing on each of the three skill sets. Residents are exposed to two matched SP cases for each of the three skill sets, one serving as a pre-test at the beginning of the rotation, the other as a post-test at the end of the rotation. The MSSRP student would: (1) score video tapes of the residents conducting a clinical interview with the SP's, using a scoring system developed specifically for this purpose; (2) develop outcome and summary measures that describe group and individual performance.
Faculty: Richard L. Guerrant, MD
Department: Medicine/Infectious Diseases
Phone: 4-5242
Title: Impact of immunogenic vaccines on nucleotides as well as AlanylGlutamine and Arginine on cell signaling in malnourishing cryptosporidial infections
Abstract: Having discovered the huge developmental impact of malnourishing diarrhea in children, our lab is focusing on understanding novel interventions to prevent or repair intestinal injury using novel immunogenic vaccines and nucleotides as well as glutamine and arginine-rich peptides. Since these may also have key anti-inflammatory as well as growth promoting effects, we shall use our tissue culture, organoid, and animal model systems to understand and optimize these effects. This work involves not only tissue culture and animal work, but potentially microarray and peptide assays and their analyses.
Faculty: Tracey R. Hoke, MD, MSc
Department: Pediatrics
Phone: 4-9119
Title: Cardiac surgery in neonates, infants, children is an ever-evolving science.
Abstract: Advances in imaging technology, surgical technique and materials, and post-operative care, all have a potential impact on clinical outcome. We seek to interrogate the Congenital Heart Surgery Database here at the University of Virginia, the National Society for Thoracic Surgery Database, and the National University Health Systems Consortium database to determine outcomes for various conditions and operations both locally and nationally. The student's role would be to prepare and submit an IRB application for this human subjects research, to participate in the analysis of aggregate data by congenital heart lesion or other grouping, and to develop/author a "white paper" describing surgical experience in terms of volume and type of surgeries (again by lesion or other grouping), and by clinical outcomes. Dr. Hoke is a pediatric cardiologist and trained epidemiologist interested in quality of care and clinical outcomes. This project is supported by the Division of Pediatric Cardiology. Opportunity is available for exposure to either congenital heart surgery or pediatric cardiology here at UVa in order to facilitate the student's understanding of the clinical issues particular to our population and practice.