Research in the Anderson laboratory focuses on cellular signaling and ionic mechanisms that cau...se 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 appear 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 more

A. Laboratory activities include the use of accelerator mass spectrometry (AMS) techniques to m...easure 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 pharmacokinetics. 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

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. view more

Barbara Slusher, M.A.S., Ph.D., leads a 20-member veteran drug discovery team of medicinal chem...ists, 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.
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The Foster Lab uses the tools of protein biochemistry and proteomics to tackle fundamental prob...lems 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.


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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. view more

Dr. Haughey directs a disease-oriented research program that address questions in basic neurobi...ology, 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 excitability.
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

Research in the Joseph Cofrancesco Jr. Lab focuses primarily on health care for HIV-positive pa...tients. 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. view more

Dr. Hua's research has centered on the development of novel MRI technologies for in vivo functi...onal 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

The Glunde lab is within the Division of Cancer Imaging Research in the Department of Radiology... and Radiological Science. The lab is developing mass spectrometry imaging as part of multimodal molecular imaging workflows to image and elucidate hypoxia-driven signaling pathways in breast cancer. They are working to further unravel the molecular basis of the aberrant choline phospholipid metabolism in cancer. The Glunde lab is developing novel optical imaging agents for multi-scale molecular imaging of lysosomes in breast tumors and discovering structural changes in Collagen I matrices and their role in breast cancer and metastasis. view more

The Penet lab is within the Division of Cancer Imaging Research in the Department of Radiology ...and Radiological Science. The lab research focuses on using multimodal imaging techniques to better understand the microenvironment and improve cancer early detection, especially in ovarian cancer. By combining MRI, MRS and optical imaging, we are studying the tumor microenvironment to understand the role of hypoxia, tumor vascularization, macromolecular transport and tumor metabolism in tumor progression, metastasis and ascites formation in orthotopic models of cancer. We also are studying the role of tumor-associated macrophages in tumor progression. view more

Our laboratory conducts basic and translational research aimed at better understanding the path...ogenesis of multiple sclerosis (MS) and the role of the immune system in CNS disease, particularly the processes that drive progressive disability such as neurodegeneration and remyelination failure. We currently have three parallel research programs: 1. Metabolism as a modulator of MS: We are studying how basic metabolic pathways regulate the immune system and how these pathways might be exploited to protect neurons and myelin-forming oligodendrocytes from injury. 2. Identifying pathways by which nitric oxide (NO) and other free radicals cause neuronal and axonal damage. Our lab is identifying specific signaling pathways initiated by NO and other free radicals that can be targeted by drugs to produce neuroprotection. 3. Modulating the innate immune system in MS: In collaboration with others at Johns Hopkins, we are studying ways to enhance the reparative functions of microglia while preventing maladaptive responses. This work has identified bryostatin-1 as a potential drug that may be re-purposed for this task. view more

The MR Research Laboratory focuses on developing and applying nuclear magnetic resonance (NMR) ...techniques and on measuring energy metabolites and metabolic fluxes with phosphorous (31P) and proton (1H) MRS in patients with ischemia, infarction and heart failure.

Specific studies include: Phosphorus MR studies of myocardial energy metabolism in human heart: We have used spatially localized phosphorus MR spectroscopy (MRS) to noninvasively measure high-energy phosphate metabolites such as ATP (adenosine triphosphate) and phosphocreatine (PCr) in the heart. The PCr/ATP ratio can change during stress-induced ischemia, and a protocol for stress-testing in the MR system has been developed which can detect the changes noninvasively in the anterior wall. Additionally, we've developed methods for noninvasively measuring the creatine kinase (CK) ATP energy supply and used it to measure the CK ATP energy supply in the healthy heart at rest and exercise, in human myocardial infarction, and in human heart failure.

Interventional MRI technology: We are developing an RF dosimeter that measures incident-specific absorption rates applied during MRI independent of the scanner and developing MRI-safe internal detectors for higher field use. Outcomes of this research include the "MRI endoscope" that provides real-time, high-resolution views of vessel anatomy and a radiometric approach to detect any local heating associated with the device.
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Researchers in the Suzanne Jan de Beur Lab are interested in bone and mineral metabolism, endoc...rinology and osteoporosis. In addition, we focus on hormonal regulators of phosphate homeostasis, parathyroid hormone signaling and the molecular basis of hypophosphatemic disorders. view more

The Barouch Lab is focused on defining the peripheral cardiovascular effects of the adipocytoki...ne leptin, which is a key to the understanding of obesity-related cardiovascular disease. Interestingly, many of the hormonal abnormalities seen in obesity are mimicked in heart failure. The research program will enhance the understanding of metabolic signaling in the heart, including the effects of leptin, exercise, sex hormones, and downstream signaling pathways on metabolism and cardiovascular function.

The lab also is working to determine the precise role of the “metabolic” beta-3 adrenergic receptor (ß3AR) in the heart and define the extent of its protective effect in obesity and in heart failure, including its role in maintaining nitric oxide synthase (NOS) coupling. Ultimately, this work will enable the exploration of a possible therapeutic role of ß3AR agonists and re-coupling of NOS in preventing adverse ventricular remodeling in obesity and in heart failure.

Lili Barouch, MD, is an associate professor of medicine in the Division of Cardiology and a member of the Advanced Heart Failure and Cardiac Transplantation group at the Johns Hopkins University School of Medicine. view more

The nervous system has extremely complex RNA processing regulation. Dysfunction of RNA metaboli...sm has emerged to play crucial roles in multiple neurological diseases. Mutations and pathologies of several RNA-binding proteins are found to be associated with neurodegeneration in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). An alternative RNA-mediated toxicity arises from microsatellite repeat instability in the human genome. The expanded repeat-containing RNAs could potentially induce neuron toxicity by disrupting protein and RNA homeostasis through various mechanisms.

The Sun Lab is interested in deciphering the RNA processing pathways altered by the ALS-causative mutants to uncover the mechanisms of toxicity and molecular basis of cell type-selective vulnerability. Another major focus of the group is to identify small molecule and genetic inhibitors of neuron toxic factors using various high-throughput screening platforms. Finally, we are also highly interested in developing novel CRISPR technique-based therapeutic strategies. We seek to translate the mechanistic findings at molecular level to therapeutic target development to advance treatment options against neurodegenerative diseases. view more

The Theresa Shapiro Laboratory studies antiparasitic chemotherapy. On a molecular basis, we are... interested in understanding the mechanism of action for existing antiparasitic agents, and in identifying vulnerable metabolic targets for much-needed, new, antiparasitic chemotherapy. Clinically, our studies are directed toward an evaluation, in humans, of the efficacy, pharmacokinetics, metabolism and safety of experimental antiparasitic drugs. view more

The Weiss Lab, which features a multi-disciplinary team at Johns Hopkins as well as at Cedars S...inai Medical Center in Los Angeles, is dedicated to identifying the most important clinical, genetic, structural, contractile and metabolic causes of sudden cardiac death as well as the means to reverse the underlying pathology and lower risk.

Current projects include research into energy metabolism in human heart failure and creatine kinase metabolism in animal models of heart failure.

Robert G. Weiss, MD, is professor of medicine, Radiology and Radiological Science, at the Johns Hopkins University. view more

Dr. Bhujwalla’s lab promotes preclinical and clinical multimodal imaging applications to unders...tand and effectively treat cancer. The lab’s work is dedicated to the applications of molecular imaging to understand cancer and the tumor environment. Significant research contributions include 1) developing ‘theranostic agents’ for image-guided targeting of cancer, including effective delivery of siRNA in combination with a prodrug enzyme 2) understanding the role of inflammation and cyclooxygenase-2 (COX-2) in cancer using molecular and functional imaging 3) developing noninvasive imaging techniques to detect COX-2 expressing in tumors 4) understanding the role of hypoxia and choline pathways to reduce the stem-like breast cancer cell burden in tumors 5) using molecular and functional imaging to understand the role of the tumor microenvironment including the extracellular matrix, hypoxia, vascularization, and choline phospholipid metabolism in prostate and breast cancer invasion and metastasis, with the ultimate goal of preventing cancer metastasis and 6) molecular and functional imaging characterization of cancer-induced cachexia to understand the cachexia-cascade and identify novel targets in the treatment of this condition. view more