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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
HPTN (HIV Prevention Trials Network) Network Laboratory (NL) is responsible for collecting, testing and reporting results from biological samples; assisting in the development and quality assurance assessment of local laboratory capacity at the Clinical Trials Units (CTUs) participating in HPTN clinical trials (www.hptn.org); and identifying and implementing state-of-the-art assays and technologies to advance the scientific agenda of the Network.
Work in the Hsin-Chieh Yeh Lab focuses on clinical trials and cohort studies of diabetes, obesity and behavioral intervention, cancer and hypertension. Recent investigations have focused on novel risk factors and complications related to obesity and type 2 diabetes, particularly lung function, smoking and cancer. We recently co-led a randomized clinical trial of tailored dietary advice for consumption of dietary supplements to lower blood pressure and improve cardiovascular disease risk factors in hypertensive urban African Americans.
How do we see, hear, and think? More specifically, how can we study living people to understand how the brain sees, hears, and thinks? Recently, magnetic resonance imaging (MRI), a powerful anatomical imaging technique widely used for clinical diagnosis, was further developed into a tool for probing brain function. By sensitizing magnetic resonance images to the changes in blood oxygenation that occur when regions of the brain are highly active, we can make "movies" that reveal the brain at work. Dr. Pekar works on the development and application of this MRI technology.
Dr. Pekar is a biophysicist who uses a variety of magnetic resonance techniques to study brain physiology and function. Dr. Pekar serves as Manager of the F.M. Kirby Research Center for Functional Brain Imaging, a research resource where imaging scientists and neuroscientists collaborate to study brain function using unique state-of-the-art techniques in a safe comfortable environment, to further develop such techni...ques, and to provide training and education. Dr. Pekar works with center staff to serve the center's users and to keep the center on the leading edge of technology.
Jennifer Lee-Summers Lab
Research in the Jennifer Lee-Summers Lab explores cerebrovascular autoregulation, particularly during anesthesia. Our previous studies have examined cerebrovascular autoregulation and blood flow in patients with hypothermia, in neonatal patients with hypoxic-ischemic encephalopathy and in pediatric patients with moyamoya disease.
Jeremy Sugarman Lab
Research in the Jeremy Sugarman Lab focuses on biomedical ethics—particularly, the application of empirical methods and evidence-based standards to the evaluation and analysis of bioethical issues. Our contributions to medical ethics and health policy include work on the ethics of informed consent, umbilical cord blood banking, stem cell research, international HIV prevention research, global health and research oversight.
Dr. Zhou's research focuses on developing new in vivo MRI and MRS methodologies to study brain function and disease. His most recent work includes absolute quantification of cerebral blood flow, quantification of functional MRI, high-resolution diffusion tensor imaging (DTI), magnetization transfer mechanism, development of chemical exchange saturation transfer (CEST) technology, brain pH MR imaging, and tissue protein MR imaging. Notably, Dr. Zhou and his colleagues invented the amide proton transfer (APT) approach for brain pH imaging and tumor protein imaging. His initial paper on brain pH imaging was published in Nature Medicine in 2003 and his most recent paper on tumor treatment effects was published in Nature Medicine in 2011. A major part of his current research is the pre-clinical and clinical imaging of brain tumors, strokes, and other neurologic disorders using the APT and other novel MRI techniques. The overall goal is to achieve the MRI contrast at the protein and peptide ...level without injection of exogenous agents and improve the diagnostic capability of MRI and the patient outcomes. view more
Jodi Segal Lab
Research in the Jodi Segal Lab focuses on developing methodologies to use observational data to understand the use of new drugs, particularly drugs for treating diabetes, blood disorders and osteoporosis. We apply advanced methods for evidence-based review and meta-analysis, and—in collaboration with Johns Hopkins biostatisticians—we have developed new methodologies for observational research (using propensity scores to adjust for covariates that change over time) and methods to account for competing risks and heterogeneity of treatment effects in analyses.
John Schroeder Lab
The John Schroeder Lab focuses on understanding the role human basophils and mast cells play in allergic reactions, as it relates not only to their secretion of potent inflammatory mediators (e.g., histamine and leukotriene C4) but also to their production of pro-inflammatory cytokines. We have long utilized human cells rather than cell lines in order to address the parameters, signal transduction and pharmacological aspects underlying clinically relevant basophil and mast cell responses. As a result, the lab has established protocols for rapidly isolating large numbers of basophils at high purity from human blood and for growing culture-derived mast cells/basophils from human progenitor cells. A variety of assays and techniques are also in place for concurrently detecting cytokines and mediators following a wide range of stimuli. These have facilitated the in vitro testing of numerous anti-allergic drugs for inhibitory activity on basophil and mast cell activation. The lab also studie...s counter-regulation between the IgE and innate immune receptors on human immature dendritic cell subtypes. view more
While there has been an explosion of knowledge about human carcinogenesis over the last 2 decades, unfortunately, this has not translated into the development of effective therapies for either preventing or treating the common human cancers. The goal of the Isaacs’ lab is to change this situation by translating theory into therapy for solid malignancies, particularly Prostate cancer. Presently, a series of drugs discovered in the Isaacs’ lab are undergoing clinical trials in patients with metastatic cancer.
The ongoing drug discovery in the lab continues to focus upon developing agents to eliminate the cancer initiating stem cells within metastatic sites of cancer. To do this, a variety of bacterial and natural product toxins are being chemically modified to produce “prodrugs” whose cytotoxicity is selectively activated by proteases produced in high levels only by cancer cells or tumor associated blood vessel cells. In this way, these prodrugs can be given systemically to metastati...c patients without un-acceptable toxicity to the host while being selectively activated to potent killing molecules within metastatic sites of cancer.
Such a “Trojan Horse” approach is also being developed using allogeneic bone marrow derived Mesenchymal Stem cells which are genetically engineered to secrete “prodrugs” so that when they are infused into the patient, they selectively “home” to sites of cancers where the appropriate enzymatic activity is present to liberate the killing toxin sterilizing the cancer “neighborhood”. view more
Research in the John Ulatowski Lab explores the regulatory mechanisms of oxygen delivery to the brain and cerebral blood flow. Our work includes developing and applying new techniques and therapies for stroke as well as non-invasive techniques for monitoring brain function, fluid management and sedation in brain injury patients. We also examine the use of novel oxygen carriers in blood. We’ve recently begun exploring new methods for perioperative and periprocedural care that would help to optimize patient safety in the future.