Medical Students
Biomedical Engineering
Sites in Education
Student Accomplishments
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Melissa Anderson | Lauren Boerboom
| Joe Burns | Michael Gutknecht
| Amelia Hufford | Evonne Johnson
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 Melissa Anderson, a Microbiology Ph.D
candidate in the lab of Dean Kedes has received a Ruth L.
Kirschstein National Research Service Award (NRSA) for Individual
Predoctoral Fellows via the National Cancer Institute
(NCI).Project Title for the Award: Characterization of the gammaherpesvirus specific tegument protein, pORF52, in the life cycle of RRV infection. Research Statement: Intensive research efforts on neurotropic alphaherpesviruses has led to a strong overall understanding of the herpesvirus family, while leaving less explored the mechanisms governing significant biological differences among the three distinct (alpha-, beta- and gamma-) subfamilies. Although sharing a conserved tri-laminar structure, the members of each subfamily possess a collection of structural (and nonstructural) proteins that is unique. We, and others, have hypothesized that these differences may lead to the distinct biology, host-pathogen interactions as well as modes of pathogenesis among members of these subfamilies. To address this issue, our laboratory has focused on the Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic human gammaherpesvirus. My project involves the molecular characterization of a single gamma-specific protein, pORF52, that we have determined lies within the middle (tegument) layer of the virion. We hypothesize that pORF52 may play an essential role in the formation of new viral particles. Previous Education: B.S., Biology, Northeastern Illinois University
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Project Title for the Award: The Roles of F-Actin Belts and Tension in Hair Cell Regeneration. Research Statement: "Humans and other mammals are vulnerable to permanent deficits of hearing and balance that arise when hair cells are killed by loud sounds, drugs, infections, and other causes. Fish, amphibians, reptiles, and birds can regenerate hair cells and recover sensory function after supporting cells divide and give rise to replacement hair cells. The unique belts of filamentous actin which bracket the apical junctions of supporting cells in the balance organs of rodents and humans become substantially reinforced postnatally. Their counterparts in chickens, however, remain thin throughout life. The time course of growth of the F-actin belts nearly perfectly correlates with a decline in supporting cell spreading and proliferation, and the belts approach their maximal thickness as the total number of hair cells in the utricular epithelium plateaus. The objectives of this project are to determine if reinforced belts of F-actin in mammalian supporting cells play a part in limiting hair cell regeneration." Related Publications: The Journal of Comparative Neurology Previous Education: B.S. Biomedical Engineering, UVA
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Research Statement: We aim to expand on the established paradigm that breast cancer progression is regulated by tumor stroma. Cells of the myeloid lineage, including macrophages, can comprise a significant proportion of the stromal cell population and function in a pro-tumor and/or anti-tumor manner. The objective of my project is to elucidate the mechanisms through which focal adhesion kinase (FAK), a non-receptor tyrosine kinase, regulates macrophage function in the context of the breast tumor microenvironment. We hypothesize that disruption of these mechanisms through FAK deletion will negatively impact the ability of macrophages to function in a tumor-promoting capacity, either by impairing the ability of the macrophages to infiltrate the tumor and/or by inhibiting macrophage functions that contribute to tumor progression and metastasis. Previous Education: M.S., Physiology, Georgetown & B.S., Biology, Duke
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Previous Education: B.S. Microbiology, Indiana University
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Project Title for the Award: Mechanisms of ERK Activation in Gammaherpesviruses. Research Statement: "The herpesvirus particle is composed of three layers, the lipid envelope, the proteinaceous tegument layer, and the highly ordered icosahedral capsid that houses the linear viral DNA. Much of what is known about the structure of herpesviruses is based solely on the prototypic alphaherpesvirus, HSV-1; however, the protein composition of the virus particle can vary based on the subfamily. Our lab is interested in characterizing the protein composition of gammaherpesviruses. Mass spectrometry data from our lab reveal that RRV contains at least 33 virally encoded proteins and a select subset of cellular proteins, including ERK. The focus of my project is the characterization of ERK within the particle of RRV and the human homolog, KSHV. In addition, we are also investigating the activation of the ERK pathway and the mechanism by which phospho-ERK levels continue to increase during de novo RRV infection." Previous Education: B.S., Biology, James Madison University
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Project Title for the Award: The Role of the Rab GAP AS 160 in Adipocyte Metabolism. Research Statement: "Major diseases associated with insulin resistance, including obesity, the metabolic syndrome, type 2 diabetes, and hypertension, have impaired regulation of glucose uptake and lipid metabolism in adipocytes. The Rab GAP (GTPase activating protein) and Akt substrate AS160 has been shown to play a role in glucose metabolism both in vitro and in vivo. The purpose of my research is to understand how AS160 regulates the trafficking of the glucose transporter GLUT4 in primary adipocytes. I plan to utilize AS160 knock out mice to determine how the lack of AS160 affects overall glucose and lipid metabolism." Previous Education: B.S., Biology, UMES
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Project Title: NFAT5-dependent Regulation of Vascular Smooth Muscle Cell Phenotypic Modulation. Research Statement: Atherosclerosis (i.e. build-up of plaque in the artery) greatly attributes to cardiovascular-related deaths, in that plaque rupture can lead to heart attack or stroke. The progression of the atherosclerotic plaque within the large arteries of the body is characterized by cholesterol accumulation and monocyte infiltration into the arterial wall, as well as vascular smooth muscle cell (SMC) migration and proliferation. My research is specifically focused on a transcription factor called the nuclear factor of activated T-cells 5 (NFAT5) and its regulation of genes involved in the maintenance of the healthy, contractile SMC as well as gene regulation in both acute and chronic vascular disease. In vivo techniques utilized in our lab include genetic mouse knockouts, rat balloon angioplasty and mouse carotid wire injury models, and ApoE-/- atherosclerosis models. The goal of our research is to further understand the mechanisms behind plaque development and SMC proliferation. Recent Honors: American Physiological Society Outstanding Student Presentation in Coordinate Regulation of Vascular Smooth Muscle Gene Expression, Cell Phenotype, and Vessel Function. Experimental Biology Annual Conference, Anaheim, CA 2010. Previous Education: B.S., Biology, Texas A&M
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Project Title for the Award: The Interaction of Hemodynamics and Bone Marrow-Derived Cells in Regulating Microvascular Remodeling. Research Statement: "We are working to understand how blood vessels
remodel themselves in order to identify key signaling pathways that aid
in vessel remodeling. By enhancing blood vessel remodeling, we can
trick the body into creating its own bypasses around blocked arteries,
potentially preventing catastrophic heart attacks and peripheral
vascular disease. Within this larger goal, I am exploring how multiple
factors work together to guide the remodeling process. These factors
include the physical forces of the blood flowing along the walls of the
vessel to the attraction of inflammatory cells. Currently, I am
developing and testing a new technique that allows us to study all of
these key factors at once. We believe that by working with the entire
system together—instead of studying each of these factors separately—we
will gain a much better understanding of the remodeling process."
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Project Title for the Award: O-GlcNAc Misregulation and Aneuploidy in Breast Cancer. Research Statement: "O-GlcNAc is a post-translational modification in metazoans that exerts control over various cellular processes, acting as a kind of nutrient sensor, as the levels and specificity of the modification vary based on cellular metabolic rate. This mechanism has been implied in the progression of type 2 diabetes, as well as aneuploidy in some cell lines. We intend to study O-GlcNAc in the context of breast cancer progression, and determine whether misregulation of its addition can bypass checkpoint control of rereplication in breast epithelial cells. Additionally we will determine whether global and specific protein levels of O-GlcNAc in breast tumors can be correlated with prognostic indicators." Previous Education: B.S., Biological
Sciences
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Meera Murgai, a Pathology Ph.D candidate in the lab of Dr. Gary Owens has received a Predoctoral Fellowship from the Mid-Atlantic Affiliate of the American Heart Association. Project Title: KLF2 is involved in phenotypic modulation of vascular cells in atherosclerotic disease. Research Statement: Atherosclerosis is a chronic vascular disease that is responsible for >40% of all deaths in Western societies where a major challenge for the field has been to identify critical regulatory genes that contribute to disease susceptibility and end stage clinical consequences including plaque rupture and myocardial infarction. We will study the role of the gene KLF2 in vascular smooth muscle cell (vSMC) involvement in the formation of atherosclerosis by first determining whether KLF2 plays a role the ability of vSMCs to react to lipids that are important to the formation of atherosclerotic plaques. We will answer this first question by eliminating KLF2 gene expression in vSMCs in culture and then examine their response to oxidized phospholipids. The second approach to our study is to ask the question of whether KLF2 gene expression plays a role in the development and progression of atherosclerotic plaques. We will this answer this second question by using a mouse model of atherosclerosis where we are able to silence the gene expression of KLF2 from vSMCs and then examine the formation of atherosclerotic plaques. Previous Education: B.S., Biology and Computer Science, Mary Washington College
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Research Statement: "My project focuses on validating tumor-associated phosphopeptides as relevant immunotherapeutic targets for melanoma. Our lab, in collaboration with Dr. Hunt's lab, has identified numerous phosphorylated peptides on cancer cell lines, and has generated phospho-specific CD8+ T cell responses for some phosphopeptides. Additionally, we want to classify phosphopeptides that are preferentially and/or differentially displayed on melanoma cell lines with particular mutations. From this, we hope to generate phospho-specific CD8+ T cell responses, optimize the immunogenicity of phosphopeptides that are weakly or non-immunogenic, and develop a xenograft melanoma model to evaluate the synergistic and/or antagonistic effects of small molecule inhibitors on phosphopeptide display in these lines." Previous Education: B.S., Biology & Psychology, Virginia Tech
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Project Title: Id3 Regulation of CCR6 and B Cell Homing in Atherosclerosis The current paradigm in the progression of atherosclerosis involves lipid deposition in the artery wall leading to recruitment of inflammatory cells such as macrophages and T cells. Recent studies provide evidence that B cells are also recruited, yet the molecular and cellular mechanisms that mediate B cell homing to the aorta are unknown. Novel preliminary data from our laboratory demonstrates that Id3 is essential for aortic B cell homing and atheroprotection. Id3 is a helix-loop-helix transcription factor implicated in B cell function, but nothing is known about its role in chemokine receptor homing. Our preliminary data further demonstrates that Id3-/-Apoe-/- mice have reduced expression of the chemokine receptor, CCR6, on B cells. Additionally, mice null for CCR6 have fewer aortic B cells. This leads us to hypothesize that loss of Id3 results in repression of CCR6 expression, and that CCR6 is essential for aortic B cell homing and atheroprotection. We aim to identify these mechanisms. Previous education: B.S., Biochemistry, University of Pittsburgh
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Project Title for the award: Elucidating the role of iNOS in left ventricular remodeling using AAV-mediated RNAi. Research Description "Acute myocardial infarction (MI) leads to impairment of left ventricular (LV) function and LV remodeling, which can result in heart failure. Early after MI, elaboration of proinflammatory cytokines and chemokines stimulates the expression of inducible nitric oxide synthase (iNOS). While iNOS is known to contribute to the production of harmful reactive oxygen species, its role after MI and in LV remodeling is controversial. We have bioengineered an adeno-associated virus (AAV) to express RNA interference (RNAi) molecules targeting iNOS. RNAi selectively reduces protein expression through endogenous regulatory mechanisms. In addition, AAV is a powerful vector for the delivery and stable expression of transgenes and RNAi and, in the case of AAV serotype 9, provides efficient, homogenous and cardiac-selective expression throughout the murine heart following one intravenous injection. Our goal is to deliver RNAi targeting iNOS to mice using AAV9 and to quantitate its impact on iNOS expression, LV remodeling and cardiac contractile function after reperfused MI." Oral Abstract Presentation of note: Piras, BA, KMR Prasad, RS Smith, BA French. Highly-Efficient In Vivo Knock-Down of Ubiquitously Expressed eGFP in the Murine Heart with siRNA Delivered by a Pseudotyped AAV9 Vector. Presented at AHA Scientific Sessions 2010, November 17. (Abstract). Previous Education:Bachelor of Biomedical Engineering, University of Minnesota; BA, University of St. Thomas
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Courtney Pollard, III a MSTP/Molecular Physiology Ph.D student in the lab of Dan Theodorescu has received a Ruth L. Kirschstein National Research Service Award (NRSA) for Individual Predoctoral Fellows via the National Cancer Institute. Project Title for the Award: The Role of SRC on RhoGDI2 Function in Bladder Cancer Metastasis. Research Statement: "In the US ~50,000 patients are diagnosed yearly with bladder cancer. 80% percent of patients present with superficial tumors which are successfully treated with local endoscopic resection. The remainder present with muscle invasive disease, commonly treated by removal of the entire bladder. Greater than 50% of patients who present with the muscle invasive subtype eventually develop lung metastases which is essentially incurable. Using co-immunoprecipitation and mass spectroscopy techniques our lab showed that Rho GDP-dissociation inhibitor 2 (RhoGDI2), a known metastasis suppressor protein, complexes and binds cellular sarcoma tyrosine kinase (Src) in human bladder cancer cells. In addition, we have shown that Src phospho-mimetic RhoGDI2 (Tyr153E) suppresses experimental in vivo metastasis more than 10 fold when compared to WT RhoGDI2. The overall aim of this project is to determine the functional interdependence of Src and RhoGDI2 in suppressing the development of bladder tumor invasion and metastasis." Related Publications: Pubmed Listings Previous Education: B.S., Biology, Morehouse College
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Related Publications: PubMed Listings Ray, BJ and Bouton, AH. Investigations into the role of Focal
Adhesion Kinase (FAK) in bone marrow-derived osteoclasts. Paper to be
submitted January 2010.
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Project Title for the Award: G Protein Mechanisms Underlying K Channel Modulation in Adrenal Glomerulosa Cells. Research Statement: "Inhibition of background K+ channels by Gαq PCRs has long been recognized as an important and widespread mechanism for controlling electrical activity in excitable cells and secretion from endocrine cells. In zona glomerulosa cells of the adrenal gland, the membrane hyperpolarization due to background K+ channels of the TASK family provides a brake on aldosterone secretion; inhibition of TASK channels by Gaq-linked Angiotensin II receptors stimulates aldosterone secretion and genetic deletion of TASK channels in mice causes primary hyperaldosteronism and hypertension. Our laboratory has recently provided evidence for a novel form of Gαq-mediated inhibition of TASK channels– inhibition is independent of PLC activation and/or PIP2 depletion. Interestingly, despite this seemingly membrane-delimited mechanism, my primary data indicate that receptor mediated TASK channel inhibition involves a diffusible messenger. This project involves extending published and preliminary observations to determine if G protein signaling mechanisms identified for cloned channels apply also to native channels, as well as using heterologous systems to test if Gaq can diffuse to cause inhibition of TASK channels." Related Presentations: "Inhibition of TASK-3 by Gaq Requires a Diffusible Second Messenger," Society for Neuroscience Annual Meeting, October 2009. Previous Education: B.S., Biology, Penn State
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Project Title for the Award: Smooth Muscle Cell Transition to a Macrophage-like State In Vivo Research Statement: "Atherosclerosis is a disease of chronic inflammation that can lead to myocardial infarction and is a leading cause of death in the world. A long standing belief in the field is that the number of macrophages compared to smooth muscle cells (SMC) within atherosclerotic lesions directly correlate with plaque stabilization and its probability of rupturing and initiating a myocardial infarction, and cardiovascular pathologists generally agree that increased SMC content in an atherosclerotic plaque is beneficial for plaque stability. However, our lab has demonstrated that SMCs are capable of down-regulating markers of contractile state SMCs, and taking on characteristics of macrophages in vitro, counter to the general assumption that inflammatory cells within lesions are principally of monocyte origin. Results of present studies tested the hypothesis that SMCs can take on a macrophage-like state in atherosclerotic lesions and that this process is in part regulated by KLF-4." Awards: ATVB Young Investigators Travel Award, April 2011 Previous Education: B.S., Biology, University of Delaware-Newark, M.S., Physiology, University of Virginia
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Project Title for the Award: Determining the Molecular Mechanism of Plectin-1 in Pancreatic Ductal Adenocarcinoma. Research Statement: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths in the United States with a 5-year survival rate of 4%. Most patients show no symptoms during early stages and are therefore diagnosed with metastatic disease. Thus, there is an urgent need for improved therapeutic options. Recently, we identified plectin-1 as a biomarker for PDAC. Plectin-1 is a large protein that crosslinks the cytoskeletal elements. Of the 60 human specimens analyzed via histology, all 60 of them were positive for plectin-1 expression while none of the normal pancreas specimens stained positive. Given its remarkable expression profile, understanding plectin-1's role in pancreatic cancer is of great importance. As most PDAC originates from K-RAS gene mutation, determining the functional role of plectin-1 and the other proteins involved in the RAS signaling network is crucial, as they are potential druggable targets. Through pharmacological inhibition of the pathways, we will elucidate the effect these proteins have on pancreatic tumor growth. Other Recent Honors: Accepted into the Teaching Resource Center's Tomorrow's Professor Today Program. Recent Publications:
Pubmed Listings
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Research Statement: "Hutchinson-Guilford Progeria Syndrome (HGPS) is
a rare and devastating premature aging disease that occurs in children.
Patients with HGPS will die of cardiovascular complications and have a
life expectancy of approximately 13 years. HGPS is caused by a mutation
in the nuclear protein Lamin A. The goal of our studies is to determine
how the mutant form of Lamin A drives cellular phenotypes. We have
discovered that HGPS patient cells have a defect in assembly of the
nuclear pore complex, the channel that mediates transport between the
nucleus and the cytoplasm. With financial support from the NSF, we will
characterize both the molecular basis of these defects and the impact
on cell physiology."
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Project Title for the Award: The Role of miRNAs in the Progression of Prostate Cancer from Androgen-Dependent to Androgen-Independent Stages. Research Statement: "miRNA is a class of small non-coding RNAs that
posttranscriptionally regulate gene expression. Aberrant expression of
miRNAs is seen in many diseases, including cancers. Prostate cancer is
the second
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Michael
Gutknecht, a Microbiology Ph.D candidate in the lab of Amy
Bouton has received a Breast Cancer Research Program (BCRP) Predoctoral
Traineeship Award via the Department of Defense's Congressionally
Directed Medical Research Program (CDMRP).
Brianne Ray,
a Microbiology Ph.D student in the lab of Amy Bouton has received a
Predoctoral Fellowship via the U.S. DOD – Army – Medical Command.
Laura Shankman,
a Physiology Ph.D candiate in the lab of Gary Owens has received a
Predoctoral Fellowship from the Mid-Atlantic Affiliate of the American
Hearth Association.
