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 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.

Our laboratory pioneers innovations at the intersection of precision neurology, neuroengineering, artificial intelligence, and data science. We develop advanced neural-AI interfaces, autonomous wearable neurotechnologies, and immersive augmented and virtual reality platforms incorporating novel multimodal neuron-sensing technologies designed to personalize diagnostics, enhance therapeutic interventions, and optimize neurological rehabilitation. Leveraging computational neuroscience, AI, and applied data science, we generate robust digital biomarkers to monitor and treat neurologic diseases in real-time. Through interdisciplinary collaborations, we aim to transform clinical practice by providing precise, interactive, and personalized neurologic care that dramatically improves patient outcomes.

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 research goals of the Functional Neurosurgery Laboratory include the development of computational models to understand how brain function is affected by neurological conditions and how this abnormal function might be corrected or minimized by neuromodulation through electrical stimulation. The lab uses data collected from patients during epilepsy monitoring or in the operating room during DBS procedures to construct and calibrate the computational models. The models can be manipulated to explore functional changes and treatment possibilities. The other primary goal of the laboratory is the development of a neuromodulation system that applies stimulation pulses at specific phases of brain oscillatory activity. This technique is being explored in the context of Parkinson's disease as well as memory function, and may lead to less invasive therapeutic treatment system with more effective stimulation.

Our group is interested in a broad array of clinical and translational investigations spanning the evaluation of basic pathophysiology in patients undergoing cardiac procedures, development and evaluation of new therapeutic strategies, and improving patient selection and outcomes following interventional procedures. We are comprised of a core group of faculty and dedicated research nurses as well as fellows, residents, and students. Projects range from investigator-initiated single-center observational studies to industry-sponsored multicenter phase 3 randomized controlled trials. We have established a database of all patients who have undergone TAVR at Johns Hopkins, which is providing the basis for several retrospective analyses and will serve as the foundation for future studies of TAVR. We are also engaged in collaborative projects with other groups from the Department of Medicine and other Departments including Cardiac Surgery, Anesthesiology, Radiology, Psychiatry, and Biomedical Engineering. Members of our group are actively involved with the Johns Hopkins Center for Bioengineering Innovation and Design (CBID) in the development of novel minimally-invasive cardiovascular devices.

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.