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Alison Moliterno Lab
The Alison Moliterno Lab studies the molecular pathogenesis of myeloproliferative disorders (MPDs), including polycythemia vera, essential thrombocytosis and idiopathic myelofibrosis. Our research is focused on the genetic and epigenetic lesions associated with MPDs, with the goal of improving diagnosis and treatment for these disorders.
We specialize in unconventional, multi-disciplinary approaches to studying the heart at the intersection of applied mathematics, physics and computer science. We focus on theory development that leads to new technology and value delivery to the society. Currently we have three research programs:
1. Precision Medicine
To develop a quantitative approach to personalized risk assessment for stroke and dementia based on patent-specific heart anatomy, function and blood flow.
Disciplines: Cardiac Hemodynamics; Medical Imaging Physics; Continuum Mechanics; Computational Fluid Dynamics
2. Information Theory
To quantify and perturb cardiac fibrillation that emerges as a macro-scale behavior of the heart from micro-scale behaviors of inter-dependent components.
Disciplines: Cardiac Electrophysiology; Spiral Wave; Information Theory; Complex Networks
3. Artificial Intelligence
To develop artificial intelligence algorithms to predict the future risk of heart attack, stroke and sudden... death, and to assist surgical interventions to prevent these outcomes.
Disciplines: Medical Imaging Physics; Artificial Intelligence; Robotically Assisted Interventions
The main focus of the Becker lab has been on the mechanisms and consequences of post-ischemic myocardial inflammation.
Genomic control of platelet function:
Aggregation of blood platelets initiates clotting in coronary arteries, the main cause of heart attacks. Our laboratory conducts experiments to understand how genes control platelet function. Through funding by the National Heart Lung and Blood Institute, we have performed candidate gene analysis, linkage studies, whole genome association studies, and now whole genome sequencing in about 2000 healthy subjects from families with early onset coronary artery disease. The subjects are siblings or offspring of an individual identified with coronary artery disease before age 60 in the GeneSTAR Research Program (Genetic Studies of Atherosclerosis Risk). We have identified a large number of common and rare genetic variants associated with platelet aggregation, and although some variants are located in genes known to be important in... the biology of platelet function, most are in non-protein coding regions of genes (introns) or in intergenic regions of the genome. To understand better how these variants influence platelet function, we created pluripotent stem cells from blood mononuclear cells in 257 genotyped GeneSTAR subjects and then transformed the stem cells to megakaryocytes, the source of platelets in the bone marrow. We have determined the entire transcriptome of these megakaryocytes to measure gene expression levels in an effort to functionally link genetic variation with platelet function. We are also interested in epigenetic effects which regulate the amount of gene transcription and resulting protein formation. We have done similar transcriptomic and proteomic studies in blood platelets as we have in stem cell-derived megakaryocytes.
Our goal is to identify new therapeutic targets for drug development to control excessive platelet aggregation and reduce the risk of heart attack in susceptible individuals. We also hope to use the genetic information to predict who is at greatest risk for platelet aggregation or bleeding, and tailor treatment to effectively apply individualized precision medicine.
The Becker laboratory also extends its cardiovascular work well beyond platelet function, as noted on the GeneSTAR Research Program website. view less
Charles W. Flexner Laboratory
A. Laboratory activities include the use of accelerator mass spectrometry (AMS) techniques to measure intracellular drugs and drugs metabolites. AMS is a highly sensitive method for detecting tracer amounts of radio-labeled molecules in cells, tissues, and body fluids. We have been able to measure intracellular zidovudine triphosphate (the active anabolite of zidovudine) in peripheral blood mononuclear cells from healthy volunteers given small doses of 14C-zidovudine, and have directly compared the sensitivity of AMS to traditional LC/MS methods carried out in our laboratory.
B. Clinical research activities investigate the clinical pharmacology of new anti-HIV therapies and drug combinations. Specific drug classes studied include HIV reverse transcriptase inhibitors, protease inhibitors, entry inhibitors (selective CCR5 and CXCR4 antagonists), and integrase inhibitors. Scientific objectives of clinical studies include characterization of early drug activity, toxicity, and pharmacok...inetics. Additional objectives are characterization of pathways of drug metabolism, and identification of clinically significant harmful and beneficial drug interactions mediated by hepatic and intestinal cytochrome P450 isoforms. view more
Colleen Koch Lab
Research in the Colleen Koch Lab covers a range of interdisciplinary topics, particularly within anesthesiology and critical care medicine. Our studies have explored topics such as hospital-acquired anemia, cardiac anesthesia, cardiac herniation, red blood cell storage and process improvement in cardiac surgery.
David Sullivan Lab
Research in the David Sullivan Lab focuses on malaria, including its diagnosis, treatment, molecular biology as it relates to iron, and pathology as it relates to severe anemia. We test and develop new malaria diagnostics — from real-time polymerase chain reaction (PCR) to novel urine and saliva detection platforms. This includes the adaptation of immuno-PCR (antibody coupled to DNA for PCR detection) to malaria and a lead blood stage drug that contains a quinine derivative used to treat malaria in the 1930s.
Edgar Miller Lab
Research in the Edgar Miller Lab focuses on nutrition, hypertension and kidney disease. Current projects include a National Heart, Lung, and Blood Institute study on dietary carbohydrate and glycemic index effects on markers of oxidative stress, inflammation and kidney function; and a National Institute of Diabetes and Digestive and Kidney Diseases randomized controlled trial that examines the effects of omega-3 fatty acid supplementation on urine protein excretion in diabetic kidney disease.
The Frederick Sieber Lab studies the impact of sedation on geriatric surgical patients—especially those undergoing orthopaedic or pelvic procedures—with the goal of preventing postoperative delirium. We are using electroencephalography to investigate the effect of sedation depth during spinal anesthesia. We are also working to determine the effects of using propofol for sedation in elderly patients as well as the effects of robotics and surgical positioning on cerebral blood flow.
Gail Daumit Lab
Research in the Gail Daumit Lab is devoted to improving overall health and decreasing premature mortality for people with serious mental illnesses, such as schizophrenia and bipolar disorder. We have conducted observational studies to determine and convey the burden of physical health problems in this vulnerable population, and are currently leading a randomized trial funded by the National Heart, Lung, and Blood Institute to test a comprehensive cardiovascular risk reduction program in people with serious mental illness.
Dr. Haughey directs a disease-oriented research program that address questions in basic neurobiology, and clinical neurology. The primary research interests of the laboratory are:
1. To identify biomarkers markers for neurodegenerative diseases including HIV-Associated Neurocognitive Disorders, Multiple Sclerosis, and Alzheimer’s disease. In these studies, blood and cerebral spinal fluid samples obtained from ongoing clinical studies are analyzed for metabolic profiles through a variety of biochemical, mass spectrometry and bioinformatic techniques. These biomarkers can then be used in the diagnosis of disease, as prognostic indicators to predict disease trajectory, or as surrogate markers to track the effectiveness of disease modifying interventions.
2. To better understand how the lipid components of neuronal, and glial membranes interact with proteins to regulate signal transduction associated with differentiation, motility, inflammatory signaling, survival, and neuronal excitab...ility.
3. To understand how extracellular vesicles (exosomes) released from brain resident cells regulate neuronal excitability, neural network activity, and peripheral immune responses to central nervous system damage and infections.
4. To develop small molecule therapeutics that regulate lipid metabolism as a neuroprotective and restorative strategy for neurodegenerative conditions. view more