Lab Night

Jogender Tushir-Singh, PhD, Assistant Professor, Department of Biochemistry and Molecular Genetics, discusses his lab work with Mini-Medical School participants.

Descriptions of Research Laboratories Participating in 2019 Lab Night:

Bauer Laboratory:  Targeting Elusive Tumor Cells
Todd W. Bauer, MD, Professor, Chief of Surgical Oncology, Department of Surgery
Description:  Our laboratory has developed a human pancreatic cancer tissue bank and mouse models using patient derived xenografts (PDXs).  We have exploited these PDX models to investigate the drivers of tumor growth, metastasis, and therapy resistance.  We have identified novel approaches to therapy focused on activation of the innate immune system for the clearance and suppression of micrometastatic disease.  Ongoing collaborations include projects to discover what happens inside the immune cell once it eats a tumor cell as well as the initial events involved as metastatic cells leave the primary pancreatic environment.

Garrett-Bakelman Laboratory:  Acute Myeloid Leukemia – Understanding the Weeds in the Bone Marrow Garden
Francine Garrett-Bakelman, MD/PhD, Assistant Professor, Biochemistry and Molecular Genetics
Description:  The Garrett-Bakelman laboratory focuses on the study of Acute Myeloid Leukemia (AML) in high risk individuals. The bone marrow is an important organ in which blood cells essential to life are produced on a daily basis. When abnormal cells arise in the bone marrow (ex. cancer cells) or external cells infiltrate the space, normal production of blood cells (hematopoiesis) is disrupted and patients can suffer from a life-threatening condition. AML is an aggressive cancer of the bone marrow that afflicts individuals of all ages.  Most patients with this disease are over the age of 60. Patients over the age of 60 and patients of all ages who are treated, achieve disease remission and then unfortunately experience recurrence (relapse), are both high risk groups. The disease mechanisms in these two high risk groups are not well understood. Understanding why the disease occurs in these patients is critical to identifying improved treatment options for them. The approach we are taking to study this question is using patient samples to generate snap shots of the biology. This includes determining what gene are affected by mutations, what genes are abnormally regulated and how the abnormal regulation occurs through next generation sequencing.  Once abnormal genes are identified, we study their function and abnormal effects in bone marrow and AML cells. Through elucidating the mechanisms that the genes use to facilitate AML biology, we aim to identify potential targets for therapeutic development in the future.

Gaultier Laboratory:  Next Generation Treatments for Brain Disorders
Alban Gaultier, PhD, Associate Professor, Neuroscience
Description:  We are a translational neuroscience lab discovering new treatments for multiple sclerosis. Our lab targets the symptoms associated with this debilitating disease, and our studies range from promoting brain repair to treating mental health issues. To achieve this ambitious mission, we combine a vast array of techniques including but not limited to the study of the gut microbiome in influencing mental health and the use of animal models of multiple sclerosis to find new ways of damaged brain repair.

Levin Laboratory: A Growing Gut Feeling
Dan Levin, MD, Assistant Professor, Department of Surgery, Division of Pediatric Surgery
Description:  The Levin laboratory focuses on developing a new treatment modality for children with Short Bowel Syndrome (SBS). This disease leads to intestinal failure resulting in profound malnutrition and dehydration. Worldwide, there are over 150, 000 children born each year with SBS and right now there isn’t a great way to treat this disease without causing further morbidity or complications for the patients. More specifically, we are investigating the role of the nervous system of the gut known as the Enteric Nervous System (ENS) and its ability to stimulate intestinal proliferation and development through a glucagon-like peptide 2 (GLP2) mediated pathway. Our plan is to develop a co-culture environment of organoids/enteroids (intestinal stem cells) and enteric neurons that will allow us to study the interactions between the different cells when treated with GLP2. We believe that unlocking this mechanism has the potential to cure thousands of children with SBS.

Lukens Laboratory:  A Gut Feeling about the Brain
John Lukens, PhD, Assistant Professor, Department of Neuroscience
Description:  Effective treatment strategies are desperately needed for most central nervous system (CNS) diseases including Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and autism.  My laboratory is focused on understanding how immunological pathways contribute to brain development, as well as mental and behavior disorders. We study the cellular and molecular pathways that contribute to brain inflammation and CNS-related tissue damage.  My laboratory is particularly interested in elucidating the mechanisms that regulate inflammatory cytokine production in the CNS in response to both tissue injury and CNS infection.  We are also exploring how the trillions of microbes in your gut, which normally co-exist peacefully with us, influence the development of our brain function and mental health. We believe that a more complete characterization of the somewhat mysterious interactions between the immune and nervous systems will lead to improved understanding of complex neurological disorders in humans and will help to identify novel and promising therapeutic targets to treat Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), CNS injury, and autism.

Lum Laboratory: Retargeting Serial Killers to Cancer Cells
Lawrence G. Lum, MD, DSc, Professor of Medicine, Director of Cellular Therapy, Scientific Director of BMT, Director of the Center for Human Therapeutics, Department of Hematology/Oncology
Description: The Lum laboratory focuses on developing bispecific antibody armed activated T cells (BATs) as an immunotherapeutic approach to treating several types of cancer, including breast, pancreatic, prostate, lung, neuroblastoma, glioblastoma, non-Hodgkin lymphoma, and multiple myeloma. BATs, which are developed from the patient’s own T cells, are manufactured by arming activated T cells with a bispecific antibody. One end of the antibody attaches to the T cell, while the other end targets tumor cells. BATs serially kill tumors and secrete immune proteins that recruit and activate endogenous immune cells, leading to in situ vaccination. BATs have been used to treat nearly 200 patients in several clinical trials over the past two decades, paving the way for FDA approval, with the ultimate goal of bringing BATs all the way from discovery to the bedside.

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.

Purow Laboratory:  Brain Cancer Puzzles
Benjamin W. Purow, MD, 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 we 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.

Singh Lab: The Second Coming of Magic Bullets and Cancer Immunotherapy
Jogender Tushir-Singh, PhD, Assistant Professor, Department of Biochemistry and Molecular Genetics, Member UVA Cancer Center
Description:  The Singh laboratory focuses on antibody engineering, dual-engaging antibodies and antibody conjugated to experimentally test novel treatment approaches for solid tumors such as ovarian, triple negative breast cancer and glioblastoma. We are making use of death receptor targeting strategies to break down solid tumor mass to effectively allow tumor penetration of immune effector cells to subsequently use immune-checkpoint antibodies. We are also interested in identifying new targets that let us attack cancer by using chimeric receptor based cell therapies. We believe that a more comprehensive immune-system independent and dependent targeting strategy is key to beat cancer and to improve long-term survival of cancer patients.

Sharlow/Lazo Lab: Thinking BIG with Small Molecules
Elizabeth Sharlow, PhD, Associate Professor, Department of Pharmacology
Description: The Sharlow Laboratory focuses on early stage drug discovery with a current primary interest in cancer (i.e., ovarian, breast, “blood” and colorectal cancers) and neurodegenerative diseases (i.e., Alzheimer’s Disease, frontotemporal dementia and amyotrophic lateral sclerosis). In the realm of cancer, we are developing a novel small molecule, JMS-053, as an anti-cancer therapeutic.  We have guided the molecule through its identification, biological evaluation and launch as a lead molecule in a small business enterprise. We are now poised for expanded, commercial development of the molecule. With respect to neurodegenerative diseases, we are developing a high content screening assay to screen for small molecules that prevent a neuron from dying thru the re-engagement of the cell cycle after Ab oligomer exposure.  If you attend this laboratory session, you will learn the challenges and excitement of small molecule drug discovery.

Stukenberg Laboratory:  Breaking Up Is Hard to Do
Todd Stukenberg, PhD, Professor, Department of Biochemistry and Molecular Genetics
Description:  Every day, 50 to 70 billion cells divide in our bodies and must do so accurately.  My laboratory studies this process, called “mitosis,” which involves chromosome segregation.  Almost half of human solid tumors lower the fidelity of mitosis so that the cells in the tumor can evolve.  Defects in chromosome segregation are the major cause of miscarriages and birth defects.  A cell has complicated biochemical machines to move chromosomes and signaling centers that sense when chromosome segregation and cell division should occur.  How are chromosomes moved?  How does a cell know when to divide?  What happens when a cell doesn’t divide properly?  Come to my lab and find out.

Yan Laboratory:  Exercise Removes Clunkers
Zhen Yan, PhD, Professor, Cardiovascular Medicine
Description: Regular exercise is the most powerful intervention in preventing and treating many of the prevalent chronic diseases. The Yan Laboratory focuses on how exercise improves the quality of mitochondria, the power plants, in skeletal muscle and other tissues with profound health benefits. We have recently discovered that a nutrient/energy sensing enzyme AMP-activated protein kinase (AMPK) is physically associated with the outer membrane of mitochondria (we call it mitoAMPK) and is activated by muscle contraction and exercise, which is essential for triggering removal of damaged/dysfunctional mitochondria. We employ the state-of-the-art technologies, such as CRISPR/Cas9-mediated gene editing and live cell imaging, to elucidate the regulation and function of mitoAMPK, which will help development of effective therapeutics to treat and prevent chronic diseases.