Basic science investigations span an array of inquiries, such as understanding the basic mechanisms underlying cardiac dyssynchrony and resynchronization in the failing heart, and beneficial influences of nitric oxide/cGMP/protein kinase G and cGMP-targeted phosphdiesterase signaling cascades on cardiac maladaptive stress remodeling. Recently, the latter has particularly focused on the role of phosphodiesterase type 5 and its pharmacologic inhibitors (e.g. sildenafi, Viagra®), on myocyte signaling cascades modulated by protein kinase G, and on the nitric oxide synthase dysregulation coupled with oxidant stress. The lab also conducts clinical research and is presently exploring new treatments for heart failure with a preserved ejection fraction, studying ventricular-arterial interaction and its role in adverse heart-vessel coupling in left heart failure and pulmonary hypertension, and testing new drug, device, and cell therapies for heart disease. A major theme has been with the use of advanced non-invasive and invasive catheterization-based methods to assess cardiac mechanics in patients.asive and invasive catheterization-based methods to assess cardiac mechanics in patients. David Kass, MD, is currently the Director at the Johns Hopkins Center for Molecular Cardiobiology and a professor in cellular and molecular medicine.

The Mathioudakis lab is focused on developing and evaluating clinical decision support systems, technology, and mHealth for diabetes prevention and management. Our lab leverages large electronic medical record databases and uses machine learning algorithms and artificial intelligence to identify patterns in clinical care associated with optimal clinical outcomes. We are interested in understanding the role that advanced diabetes technologies can play in improving health outcomes for patients with diabetes. Our lab has published extensively on outcomes related to diabetes prevention and diabetes management and outcomes. Based on data from our long-term (over 10 year) clinic-based prospective cohort study from the Johns Hopkins Multidisciplinary Diabetic Foot and Wound Clinic, we have published extensively on clinical predictors and outcomes of patients with diabetic foot ulcers, focusing specifically on the role that glycemic control plays in patients with this complication. Healthcare disparities exist throughout medicine, but are particularly prominent in diabetes; our lab has evaluated healthcare inequities in diabetes outcomes and is developing and evaluating strategies to overcome them. In addition to identify optimal management approach to diabetes and its complications, our lab is interested in development and evaluation of innovative technology approaches to diabetes prevention.

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.

The Li Gao Lab researches functional genomics, molecular genetics and epigenetics of complex cardiopulmonary and allergic diseases, with a focus on translational research applying fundamental genetic insight into the clinical setting. Current research includes implementation of high-throughput technologies in the fields of genome-wide association studies (GWAS), massively parallel sequencing, gene expression analysis, epigenetic mapping and integrative genomics in ongoing research of complex lung diseases and allergic diseases including asthma, atopic dermatitis (AD), pulmonary arterial hypertension, COPD, sepsis and acute lung injury/ARDS; and epigenetic contributions to pulmonary arterial hypertension associated with systemic sclerosis.

In the Lee Martin Laboratory, we are testing the hypothesis that selective vulnerability--the phenomenon in which only certain groups of neurons degenerate in adult onset neurological disorders like amyotrophic lateral sclerosis and Alzheimer's disease--is dictated by brain regional connectivity, mitochondrial function and oxidative stress. We believe it is mediated by excitotoxic cell death resulting from abnormalities in excitatory glutamatergic signal transduction pathways, including glutamate transporters and glutamate receptors as well as their downstream intracellular signaling molecules. We are also investigating the contribution of neuronal/glial apoptosis and necrosis as cell death pathways in animal (including transgenic mice) models of acute and progressive neurodegeneration. We use a variety of anatomical and molecular neurobiological approaches, including neuronal tract-tracing techniques, immunocytochemistry, immunoblotting, antipeptide antibody production, transmission electron microscopy and DNA analysis to determine the precise regional and cellular vulnerabilities and the synaptic and molecular mechanisms that result in selective neuronal degeneration.

The Michelle Eakin Lab conducts research on behavioral science and adherence and asthma outcomes in inner-city children. Our studies into behavioral science have included exploring the impact of medication adherence on lung health outcomes in patients with cystic fibrosis, disparities in anti-hypertensive medication adherence in adolescents and other key topics. We also investigate methods for improving asthma care and treatment as well as health disparities among various ethnicities, particularly in pediatric patients.

Research in the Mary Fissell Lab looks at the ways in which average people in early modern England understood health, healing and the natural world. In an ongoing study of vernacular knowledge (ideas about the natural world that ordinary people created, shaped and used), we are examining the popular medical book Aristotle's Masterpiece, first published in 1684. Research has also focused on health care for the poor in 18th-century urban Britain and on how ordinary people learned about their bodies from inexpensive print publications.

Our laboratory conducts basic and translational research aimed at better understanding the pathogenesis 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.

Our Molecular Oncology lab seeks to understand the genomic wiring of response and resistance to immunotherapy through integrative genomic, transcriptomic, single-cell and liquid biopsy analyses of tumor and immune evolution. Through comprehensive exome-wide sequence and genome-wide structural genomic analyses we have discovered that tumor cells evade immune surveillance by elimination of immunogenic mutations and associated neoantigens through chromosomal deletions. Additionally, we have developed non-invasive molecular platforms that incorporate ultra-sensitive measurements of circulating cell-free tumor DNA (ctDNA) to assess clonal dynamics during immunotherapy. These approaches have revealed distinct dynamic ctDNA and T cell repertoire patterns of clinical response and resistance that are superior to radiographic response assessments. Our work has provided the foundation for a molecular response-adaptive clinical trial, where therapeutic decisions are made not based on imaging but based on molecular responses derived from liquid biopsies. Overall, our group focuses on studying the temporal and spatial order of the metastatic and immune cascade under the selective pressure of immune checkpoint blockade with the ultimate goal to translate this knowledge into “next-generation” clinical trials and change the way oncologists select patients for immunotherapy.

Established in 2004, the MRB Molecular Imaging Service Center and Cancer Functional Imaging Core provides comprehensive molecular and functional imaging infrastructure to support the imaging research needs of the Johns Hopkins University faculty. Approximately 55-65 different Principal Investigators use the center annually. The MRB Molecular Imaging Service Center is located behind the barrier within the transgenic animal facility in the basement of MRB. The MRB location houses a 9.4T MRI/S scanner for magnetic resonance imaging and spectroscopy, an Olympus multiphoton microscope with in vivo imaging capability, a PET-CT scanner, a PET-SPECT scanner, and a SPECT-CT scanner for nuclear imaging, multiple optical imaging scanners including an IVIS Spectrum, and a LI COR near infrared scanner, and an ultrasound scanner. A brand new satellite facility in CRB2-LB03 opens in 2019 to house a simultaneous 7T PET-MR scanner, as well as additional imaging equipment, to meet the growing molecular and functional imaging research needs of investigators. To image with us, MRB Animal Facility training and Imaging Center Orientation are required to obtain access to the MRB Animal Facility and to the MRB Molecular Imaging Center (Suite B14). The MRB Animal Facility training group meets at 9:30 am on Thursdays at the Turner fountain/MRB elevator lobby. The Imaging Center orientation group meets at 1 pm on Thursdays at the Turner fountain, and orientation takes approximately 30 min. Please keep in mind that obtaining access to both facilities requires time, so please plan in advance.