The Nicholas Flavahan Lab primarily researches the cellular interactions and subcellular signal...ing pathways that control normal vascular function and regulate the initiation of vascular disease. We use biochemical and molecular analyses of cellular mediators and cell signaling mechanisms in cultured vascular cells, while also conducting physiological assessments and fluorescent microscopic imaging of signaling systems in isolated blood vessels. A major component of our research involves aterioles, tiny blood vessles that are responsible for controlling the peripheral resistance of the cardiovascular system, which help determine organ blood flow. view more

How do brain dynamics give rise to our sensory experience of the world? The O'Connor lab works ...to answer this question by taking advantage of the fact that key architectural features of the mammalian brain are similar across species. This allows us to leverage the power of mouse genetics to monitor and manipulate genetically and functionally defined brain circuits during perception. We train mice to perform simple perceptual tasks. By using quantitative behavior, optogenetic and chemical-genetic gain- and loss-of-function perturbations, in vivo two-photon imaging, and electrophysiology, we assemble a description of the relationship between neural circuit function and perception. We work in the mouse tactile system to capitalize on an accessible mammalian circuit with a precise mapping between the sensory periphery and multiple brain areas. Our mission is to reveal the neural circuit foundations of sensory perception; to provide a framework to understand how circuit dysfunction causes mental and behavioral aspects of neuropsychiatric illness; and to help others fulfill creative potential and contribute to human knowledge. view more

The O’Rourke Lab uses an integrated approach to study the biophysics and physiology of cardiac ...cells in normal and diseased states.

Research in our lab has incorporated mitochondrial energetics, Ca2+ dynamics, and electrophysiology to provide tools for studying how defective function of one component of the cell can lead to catastrophic effects on whole cell and whole organ function. By understanding the links between Ca2+, electrical excitability and energy production, we hope to understand the cellular basis of cardiac arrhythmias, ischemia-reperfusion injury, and sudden death.

We use state-of-the-art techniques, including single-channel and whole-cell patch clamp, microfluorimetry, conventional and two-photon fluorescence imaging, and molecular biology to study the structure and function of single proteins to the intact muscle. Experimental results are compared with simulations of computational models in order to understand the findings in the context of the system as a whole.

Ongoing studies in our lab are focused on identifying the specific molecular targets modified by oxidative or ischemic stress and how they affect mitochondrial and whole heart function.

The motivation for all of the work is to understand
• how the molecular details of the heart cell work together to maintain function and
• how the synchronization of the parts can go wrong

Rational strategies can then be devised to correct dysfunction during the progression of disease through a comprehensive understanding of basic mechanisms.

Brian O’Rourke, PhD, is a professor in the Division of Cardiology and Vice Chair of Basic and Translational Research, Department of Medicine, at the Johns Hopkins University. view more

The lab’s assets include three MRI systems available for pediatric studies, cardiac imaging pro...cessing, cardiovascular imaging and therapeutic ultrasound. A robust echocardiogram program conducts 10,000 transthoracic echocardiograms and 1,300 fetal echocardiograms per year, and maintains a database with 10 years of data. view more

Psychiatric Neuroimaging (PNI) is active in neuropsychiatric research using imaging methods suc...h as MRI, fMRI, PET and DTI to understand the mechanisms and brain networks underlying human cognition. PNI faculty have published hundreds of papers on a variety of brain disorders which include but are not limited to Alzheimer's disease, Parkinson's disease, bipolar disorder, and eating disorders. Faculty in the division have been awarded numerous peer-reviewed grants by the National Institutes of Health, foundations and other funding organizations.
view more

The main research goals of my laboratory are: (1) to identify and study the biology of novel ca...ncer selective targets whose enzymatic function can be exploited for therapeutic and diagnostic purposes; (2) to develop methods to target novel agents for activiation by these cancer selective targets while avoiding or minimizing systemic toxicity; (3) to develop novel agents for imaging cancer sites at earliest stages. To accomplish these objectives the lab has originally focused on the development of prodrugs or protoxins that are inactive when given systemically via the blood and only become activated by tumor or tissue specific proteases present within sites of tumor. Using this approach, we are developing therapies targeted for activation by the serine proteases prostate-specific antigen (PSA), human glandular kallikrein 2 (hK2) and fibroblast activation protein (FAP) as well as the membrane carboxypeptidase prostate-specific membrane antigen (PSMA). One such approach developed in the lab consists of a potent bacterial protoxin that we have reengineered to be selectively activated by PSA within the Prostate. This PSA-activated toxin is currently being tested clinically as treatment for men with recurrent prostate cancer following radiation therapy. In a related approach, a novel peptide-cytotoxin prodrug candidate that is activated by PSMA has been identified and is this prodrug candidate is now entering early phase clinical development. In addition, we have also identified a series of potent inhibitors of PSA that are now under study as drug targeting and imaging agents to be used in the treatment and detection of prostate cancer.
view more

The Shanthini Sockanathan Laboratory uses the developing spinal cord as our major paradigm to d...efine the mechanisms that maintain an undifferentiated progenitor state and the molecular pathways that trigger their differentiation into neurons and glia. The major focus of the lab is the study of a new family of six-transmembrane proteins (6-TM GDEs) that play key roles in regulating neuronal and glial differentiation in the spinal cord. We recently discovered that the 6-TM GDEs release GPI-anchored proteins from the cell surface through cleavage of the GPI-anchor. This discovery identifies 6-TM GDEs as the first vertebrate membrane bound GPI-cleaving enzymes that work at the cell surface to regulate GPI-anchored protein function. Current work in the lab involves defining how the 6-TM GDEs regulate cellular signaling events that control neuronal and glial differentiation and function, with a major focus on how GDE dysfunction relates to the onset and progression of disease. To solve these questions, we use an integrated approach that includes in vivo models, imaging, molecular biology, biochemistry, developmental biology, genetics and behavior. view more

Shelby Kutty, M.D., Ph.D., is an authority on cardiovascular imaging, including echocardiograph...y, magnetic resonance imaging and computed tomography of congenital heart disease. His areas of academic interest have focused on myocardial function assessment, therapeutic ultrasound and cardiovascular outcomes. Kutty’s research includes developing new imaging technology applications such as a smartphone application that uses patients’ echocardiographic images to track their progress. His work gives pediatric cardiologists better ways to predict outcomes in their patients and provide the most effective and appropriate treatments. view more

The Sujatha Kannan Lab works to develop therapeutic strategies for preventing perinatal brain i...njuries from occurring during development. We use a unique combination of nanotechnology, animal model development and in vivo imaging to better understand the mechanism and progression of cellular and metabolic conditions that lead to perinatal brain injury, with a focus on autism and cerebral palsy. view more