Below you will find descriptions of labs featured
in Mini-Medical School
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Annex Laboratory: Go with the Flow
Brian H. Annex, MD, George A. Beller, MD Lantheus Medical Imaging Distinguished Professor of Cardiovascular Medicine, Professor of Medicine, Chief, Cardiovascular Medicine, Department of Medicine
Description: Dr. Annex's clinical and
research interests include a multidisciplinary program in angiogenesis
(the growth of new blood vessels) that is focused mainly on peripheral
arterial disease (PAD), in which blockages in arteries cause a series
of clinical problems. His group is involved in a number of
bench-to-bedside studies, including investigations of the causes of
blockages in arteries outside the heart, including the genetic basis
for the differences in response between individuals, and, in the case
of the legs, the response of the muscle and new arterial growth that
follow the blockages, and the impact that diabetes mellitus plays in
among the array of studies are gene therapies and clinical investigations to promote blood vessel growth in patients with PAD. Among the gene therapy targets under investigation are several candidate genes, as well as several micro-RNAs. The lab is also studying the effects of exercise training, and uses pre-clinical models of PAD.
Berr Laboratory: High Resolution Imaging of
Mice: A Picture Is Worth a Thousand Words
Stuart S. Berr, PhD, Professor of Research, Department of Radiology and Medical Imaging
Description: Mice have become the most widely used animal for modeling human disease. In order to follow disease growth and the effects of novel treatments in mice noninvasively, imaging instruments have recently been developed that duplicate those found in modern radiology suites for human imaging. These include magnetic resonance imaging (MRI), X-ray computed tomography (CT), positron emission tomography (PET), and single photon emission computed tomography (SPECT). We also have scanners that can image visible light. These can be used to track cells that have been labeled with a gene from the Firefly that causes the cells to glow in the dark. We also have an ultrasound device called MR-Guided Focused Ultrasound (MRgFUS) that can be used to kill abnormal cells by heating them under MRI guidance. MRgFUS has recently been applied to treat uterine fibroids and essential tremor in humans. We will discuss these imaging modalities and provide some example images using the MRI scanner.
Bland Laboratory: Fly Fishing
Michelle L. Bland, PhD, Assistant Professor, Department of Pharmacology
Description: As the obesity epidemic rages on, it leaves in its wake an increase in the prevalence of insulin resistance and type 2 diabetes. Many scientists believe that inflammation of obese fat tissue is the link between expanded fat mass and diabetes. We have modeled these processes using the lowly fruit fly and have found that turning on the immune system in this animal blunts its ability to respond to insulin signals. We use the awesome arsenal of genetic tools available in the fly in an effort to find the genes that link activation of the immune system with inhibition of insulin signaling. The goal is to find the connections and see whether they persist in mammals. If so, our research could provide an unbiased approach to the discovery of new drug targets to treat a serious metabolic disease.
Blemker Laboratory: What Do Speech Disorders, Presbyopia, Cerebral Palsy, and Muscular Dystrophies Have in Common?
Silvia Salinas Blemker, PhD, Associate Professor,
Departments of Biomedical Engineering, Mechanical & Aerospace
Engineering, and Orthopaedic Surgery
Description: What do speech disorders, presbyopia, cerebral palsy, and muscular dystrophies all have in common? Other than being debilitating health conditions that affect millions of people, these clinical problems all involve impairment in skeletal muscle. Skeletal muscles are extraordinarily adapted motors that enable us to perform many important functions, from walking to sight to speech. How is each muscle’s structure adapted to perform its specialized function in the human body? How can a maladapted muscle be restored to perform its specific function? The goal of Multi-Scale Muscle Mechanophysiology (“M3”) Lab’s research is to use multi-scale computational and experimental approaches in order to answer the above questions and ultimately lead to improved treatments for muscle-related clinical problems. In this lab tour, we will demonstrate the experimental and modeling methods used in our lab and describe some recent examples of how these experiments/models have led to clinically relevant insights.
Cross Laboratory: Could Broccoli Prevent Cancer?
Janet V. Cross, PhD, Interim Assistant Dean for Graduate Research and Training, Director, Molecular and Cellular Basis of Disease Graduate Program, Associate Professor,
Department of Pathology
Description: The central objective of my lab is to understand how cancers co-opt aspects of the immune system to promote tumor growth and metastasis. Specifically, we focus on the role of a protein called the Macrophage Migration Inhibitory Factor (MIF). We identified MIF as a target for inhibition by a class of cancer preventive agents present in fresh vegetables, including broccoli. MIF is produced by many cancers and higher MIF levels correlate with an increased likelihood of metastatic disease and a poor outcome for the patient. These observations suggested that MIF may be contributing to cancer progression. Using a mouse model of breast cancer, we have established that MIF promotes tumor growth and is required for tumor metastasis and that it functions by influencing the host immune system. We demonstrated that treating tumor-bearing mice with our MIF inhibitory natural compound reverses the MIF-dependent changes in the immune response, suggesting that we may be able to target MIF to prevent tumor progression. Ongoing work in our lab is focused on further understanding the pathways through which MIF regulates the immune response to promote tumor progression. In parallel, we continue to evaluate the potential utility of our inhibitor as a therapeutic approach for cancer patients.
Fiske Drug Discovery Laboratory: Discovering New Drugs
Elizabeth R. Sharlow, PhD, Associate Professor of Research, Department of Pharmacology
Description: This is perhaps the golden era for the discovery of new drugs. Armed with powerful new information about the composition of your genome, the elaborate signaling pathways that participate in disease processes, and advanced technologies to detect bodily changes, academic laboratories are increasingly participating in every aspect of drug discovery. In your visit to this laboratory, you will see how scientists identify and validate drug targets and how they search for and design new therapeutic molecules. You will learn to appreciate the excitement and challenges in finding a new drug, including the use of automation and high throughput screening, and why there is such a high failure rate in drug development. We will discuss strategies for finding new drugs for cancer, Alzheimer’s disease, and neglected diseases.
Flow Cytometry Core Facility: Sensing and Sorting Cells
Michael Solga, MS, Lab Supervisor, Flow Cytometry Core Facility
Description: The Flow Cytometry Core (FCC) is an advanced shared UVA resource that provides our investigators access to unique laser-based instruments that are used to rapidly probe hundreds of thousands of individual cells in just a few minutes for differences in cell surface and intracellular proteins, DNA and other macromolecules. Visiting our laboratory you will have an opportunity to see how this powerful technology can be used to study even minor differences in a variety of disease states, such as cancer, infectious disease, autoimmunity, and allergies. We can also separate different cell populations for further interrogation. Mass and imaging cytometry enable scientists and clinicians to better understand the causes of diseases and to discover how new treatments work.
Tajie Harris Laboratory: Don’t Be Cavalier about Rogue Cells
Tajie H. Harris, PhD, Assistant Professor, Center for Brain Immunology and Glia,
Department of Neuroscience
Description: The immune system is constantly in motion and ready to detect a microbe or a rogue cell in every organ of the body, including the brain. For decades, we have known that
the immune system works in a unique way in the brain versus other parts of the body. More recently, the immune system has been implicated in numerous neurological disorders and neurodegenerative diseases, yet we are still learning how the immune system operates in the brain. Thus, the Harris laboratory watches immune cells move in real time using highly specialized microscopes. We identify how immune cells seek and destroy pathogens. With our colleagues at UVA, we also recently discovered structures in the brain that were thought to be missing. These newly discovered lymphatic vessels may explain why the immune system is slow to respond in the brain. The goal of the Harris laboratory is to find ways to make the immune system work better or to be less destructive in the brain, which will lead to the development of new treatments for diseases that affect the brain.
Thurl Harris Laboratory: Modern Obesity: A Greatly Expanding Problem for Diabetes
Thurl E. Harris, PhD, Associate Professor and Director of Graduate Studies,
Department of Pharmacology
Description: As Paleolithic hunter gatherers, the human diet was relatively low in fats and simple carbohydrates. Technological advances, beginning with the agricultural revolution
12,000 years ago and culminating with the mechanization of food production in the last century, have provided a significant portion of the world’s population with access to inexpensive, energy-dense food. In the modern age the ready availability of carbohydrates and fats, combined with a large reduction in physical labor, has led to a predictable rise in obesity. By the year 2015 it is estimated that 34% of the U.S. population will be characterized as overweight (B.M.I. of 25-30), and another 41% will be obese (B.M.I.>30), giving an astonishing 3 out 4 Americans defined as overweight or obese. As an underlying risk factor for type 2 diabetes and cardiovascular disease, understanding how obesity promotes the development of these diseases is of extreme importance for worldwide health. Food intake triggers the release of insulin, an anabolic hormone that promotes nutrient storage and protein synthesis. Our laboratory is interested in the mechanisms underlying the storage of carbohydrates and fats as triacylglycerol (TAG) in adipose tissue, their subsequent release as glycerol and fatty acids, and the dysregulation of insulin signaling that occurs during obesity.
Herr Laboratory: Signatures of Sperm
John C. Herr, PhD (assisted by Dr. Jagathpala Shetty, Senior Scientist), Professor of Cell Biology, Urology and Biomedical Engineering, Departments of Cell Biology, Urology & Biomedical Engineering
Description: Dr. Herr’s research team dissects the anatomy of molecules involved in the formation of sperm and eggs. They study sperm development in the testis and egg development in the ovary and the process of fertilization. The team always keeps a weather eye tuned to possible clinical applications of their findings. During this tour, Dr. Herr will talk about the discoveries that led to the first FDA approved home test for monitoring male infertility, SpermCheck Fertility. This home immunodiagnostic test is now found on the family planning shelves at Walgreens, Rite Aid, and CVS. The test was discovered at UVA and built around UVA patents on a sperm specific biomarker protein, SP-10. Students will learn about spermiogenesis in the testis, meet and greet the SP-10 protein, be introduced to the concept of biomarkers and analytes, understand what monoclonal antibodies are and how they can be used as reagents, understand how antibody-based home tests work, and actually perform a SpermCheck Fertility test in the laboratory.
Landen Laboratory: Why Don’t Cancer Drugs Always Work?
Charles “Chip” Landen, Jr., MD, MS, Associate Professor, Department of Obstetrics and Gynecology
Description: We all expect our drugs to work, but sometimes they fail us. Answering that profound question is one of the goals of my laboratory. We primarily focus on ovarian cancer, examining the mechanisms responsible for resistance to drugs. We also try to understand how the complex differences in tumor cells, something we call heterogeneity, leads small populations of cells to survive therapy and cause recurrence. Visiting my laboratory you will learn about cancer stem cells, pathways that lead to self-digestion pathways that can lead to unwanted tumor cell survival. We work with patient samples, cell lines, and mouse models, looking for new therapies that might target the tumor cell populations that either acquire or naturally are resistant to our current therapies.
McNamara Laboratory: Fighting Fat
Coleen A. McNamara, MD, Edward W. and Betty Knight Scripps Professor of Internal Medicine; Professor of Medicine and Cardiovascular Medicine, Associate Professor, Molecular Physiology and Biological Physics, Vice Chair for Faculty Development/Medical Education, Department of Medicine
Description: In recent years, obesity and diabetes have reached epidemic proportions. These diseases have many health consequences including stroke, heart attack, and peripheral vascular disease. Common to all of these is atherosclerosis, which is the process by which lipids, cells, and fibrous elements accumulate within the walls of arteries. Coordinated gene expression is essential to maintain normal vascular tissue structure and function, and many transcription factors regulate these processes. Our lab has identified the transcription factor Id3 as a major regulator of atherosclerosis and obesity.
Peirce-Cottler Laboratory: Tissue Engineering for Treating Diabetes
Scott Seaman, PhD Candidate, Molly Kelly-Goss, PhD Candidate, Kyle Martin, PhD Candidate, Department of Biomedical Engineering
Description: The Peirce-Cottler Laboratory is a biomedical engineering laboratory at UVA that studies vascular growth and remodeling by combining experimental and computational systems and bioengineering approaches in order to develop new therapies for tissue engineering. We seek to understand how the smallest blood vessels in our body adapt during health and disease. We then use this knowledge to engineer adult stem cell treatments and identify new drug targets that can affect microvascular growth to regenerate tissues in the body. Our active research areas include diabetes, ischemic disease (stroke, heart disease, and peripheral vascular disease), and obesity.
Purow Laboratory: Brain Cancer Puzzles
Benjamin W. Purow, MD, Associate Professor, Department of Neurology
Description: The Purow laboratory focuses in particular on new treatment approaches for glioblastoma, an extremely aggressive, incurable, and complex brain cancer. One approach we
are taking to crippling the complex genetic circuitry of glioblastoma is the delivery of tumor-suppressive microRNAs, small pieces of RNA encoded in our DNA that in some cases block multiple cancer pathways. We are also identifying new targets that let us attack cancer at multiple levels, and are excited about the potential of one called Diacylglycerol kinase alpha (DGKA). The Purow laboratory is repurposing an abandoned drug as a novel DGKA inhibitor—potentially allowing for much faster translation of DGKA inhibition to the clinic—and is also working to repurpose other existing drugs for their anticancer potential.