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Research in the Anderson laboratory focuses on cellular signaling and ionic mechanisms that cause heart failure, arrhythmias and sudden cardiac death, major public health problems worldwide. Primary focus is on the multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII). The laboratory identified CaMKII as an important pro-arrhythmic and pro-cardiomyopathic signal, and its studies have provided proof of concept evidence motivating active efforts in biotech and the pharmaceutical industry to develop therapeutic CaMKII inhibitory drugs to treat heart failure and arrhythmias.
Under physiological conditions, CaMKII is important for excitation-contraction coupling and fight or flight increases in heart rate. However, myocardial CaMKII is excessively activated during disease conditions where it contributes to loss of intracellular Ca2+ homeostasis, membrane hyperexcitability, premature cell death, and hypertrophic and inflammatory transcription. These downstream targets a...ppear to contribute coordinately and decisively to heart failure and arrhythmias. Recently, researchers developed evidence that CaMKII also participates in asthma.
Efforts at the laboratory, funded by grants from the National Institutes of Health, are highly collaborative and involve undergraduate assistants, graduate students, postdoctoral fellows and faculty. Key areas of focus are:
• Ion channel biology and arrhythmias
• Cardiac pacemaker physiology and disease
• Molecular physiology of CaMKII
• Myocardial and mitochondrial metabolism
• CaMKII and reactive oxygen species in asthma
Mark Anderson, MD, is the William Osler Professor of Medicine, the director of the Department of Medicine in the Johns Hopkins University School of Medicine and physician-in-chief of The Johns Hopkins Hospital. 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 less
Work in the Courtney Robertson Lab is focused on identifying interventions that could minimize the neurological deficits that can persist after pediatric traumatic brain injury (TBI). One study used a preclinical model to examine potential disruption of mitochondrial function and alterations in cerebral metabolism. It was found that a substantial amount of mitochondrial dysfunction is present in the first six hours after TBI. In addition, we are using nuclear magnetic resonance spectroscopy to evaluate global and regional alterations in brain metabolism after TBI. We're also collaborating with researchers at the University of Pennsylvania to compare mitochondrial function after head injury in different clinically relevant models.
Barbara Slusher, M.A.S., Ph.D., leads a 20-member veteran drug discovery team of medicinal chemists, assay developers, pharmacologists, toxicologists and pharmacokinetic/drug metabolism experts, who identify novel drug targets arising from JHU faculty’s research and translate them into new, small molecule drug therapies.
Her team collaborates extensively with faculty at the Bloomberg~Kimmel Institute for Cancer Immunotherapy and leads the BKI immunotherapy drug discovery core, aimed at developing new immune-targeting drug therapies for laboratory and clinical testing at Johns Hopkins.
The Foster Lab uses the tools of protein biochemistry and proteomics to tackle fundamental problems in the fields of cardiac preconditioning and heart failure. Protein networks are perturbed in heart disease in a manner that correlates only weakly with changes in mRNA transcripts. Moreover, proteomic techniques afford the systematic assessment of post-translational modifications that regulate the activity of proteins responsible for every aspect of heart function from electrical excitation to contraction and metabolism. Understanding the status of protein networks in the diseased state is, therefore, key to discovering new therapies.
D. Brian Foster, Ph.D., is an assistant professor of medicine in the division of cardiology, and serves as Director of the Laboratory of Cardiovascular Biochemistry at the Johns Hopkins University School of Medicine.
Frederick Anokye-Danso Lab
The Frederick Anokye-Danso Lab investigates the biological pathways at work in the separation of human pluripotent stem cells into adipocytes and pancreatic beta cells. We focus in particular on determinant factors of obesity and metabolic dysfunction, such as the P72R polymorphism of p53. We also conduct research on the reprogramming of somatic cells into pluripotent stem cells using miRNAs.
Guang William Wong Lab
The Wong Lab seeks to understand mechanisms employed by cells and tissues to maintain metabolic homeostasis. We are currently addressing how adipose- and skeletal muscle-derived hormones (adipokines and myokines), discovered in our lab, regulate tissue crosstalk and signaling pathways to control energy metabolism. We use transgenic and knockout mouse models, as well as cell culture systems, to address the role of the CTRP family of hormones in physiological and disease states. We also aim to identify the receptors that mediate the biological functions of CTRPs.
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 less
Joseph Cofrancesco Jr. Lab
Research in the Joseph Cofrancesco Jr. Lab focuses primarily on health care for HIV-positive patients. Our recent studies have explored topics such as HIV antiretroviral treatments, HIV resistance and the long-term complications of HIV treatment. In addition, we are part of the U.S. Fat Redistribution and Metabolism (FRAM) study and have had a long-standing involvement in projects that examine metabolic and fat complications in Thailand.
Dr. Hua's research has centered on the development of novel MRI technologies for in vivo functional and physiological imaging in the brain, and the application of such methods for studies in healthy and diseased brains. These include the development of human and animal MRI methods to measure functional brain activities, cerebral perfusion and oxygen metabolism at high (3 Tesla) and ultra-high (7 Tesla and above) magnetic fields. He is particularly interested in novel MRI approaches to image small blood and lymphatic vessels in the brain. Collaborating with clinical investigators, these techniques have been applied 1) to detect functional, vascular and metabolic abnormalities in the brain in neurodegenerative diseases such as Huntingdon's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD) and mental disorders such as schizophrenia; and 2) to map brain functions and cerebrovascular reactivity for presurgical planning in patients with vascular malformations, brain tumors and... epilepsy. view more