Complexity in signaling networks is often derived from co-opting one set of molecules for multiple operations. Understanding how cells achieve such sophisticated processing using a finite set of molecules within a confined space--what we call the ""signaling paradox""--is critical to biology and engineering as well as the emerging field of synthetic biology. In the Inoue Lab, we have recently developed a series of chemical-molecular tools that allow for inducible, quick-onset and specific perturbation of various signaling molecules. Using this novel technique in conjunction with fluorescence imaging, microfabricated devices, quantitative analysis and computational modeling, we are dissecting intricate signaling networks. In particular, we investigate positive-feedback mechanisms underlying the initiation of neutrophil chemotaxis (known as symmetry breaking), as well as spatio-temporally compartmentalized signaling of Ras and membrane lipids such as phosphoinositides. In parallel, we also try to understand how cell morphology affects biochemical pathways inside cells. Ultimately, we will generate completely orthogonal machinery in cells to achieve existing, as well as novel, cellular functions. Our synthetic, multidisciplinary approach will elucidate the signaling paradox created by nature.

The Caterina lab is focused on dissecting mechanisms underlying acute and chronic pain sensation. We use a wide range of approaches, including mouse genetics, imaging, electrophysiology, behavior, cell culture, biochemistry and neuroanatomy to tease apart the molecular and cellular contributors to pathological pain sensation. A few of the current projects in the lab focus on defining the roles of specific subpopulations of neuronal and non-neuronal cells to pain sensation, defining the role of RNA binding proteins in the development and maintenance of neuropathic pain, and understanding how rare skin diseases known as palmoplantar keratodermas lead to severe pain in the hands and feet.

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.

The research conducted in the Mumm Lab (Dept. of Ophthalmology, Wilmer Eye Institute) is focused on understanding how neural circuits are formed, how they function, and how they can be regenerated, to develop new therapies for retinal regeneration. Toward that end, we investigate the development, function, and regeneration of disease-relevant neurons and neural circuits responsible for vision. An emphasis is placed on translating what can be learned in regenerative model systems to develop novel therapies for stimulating dormant regenerative capacities in humans, Therefore, we apply what we learn from a naturally regenerative species, the zebrafish, toward the development of novel therapies for restoring visual function to patients. We place an emphasis on unique perspectives zebrafish afford to biological studies, such as in vivo time-lapse imaging of cellular behaviors and cell-cell interactions, and high-throughput chemical and genetic screening. We have pioneered several technologies to support this work including multicolor imaging of neural circuit formation, a selective cell ablation methodology, and a quantitative high-throughput phenotypic screening platform. Together, these approaches are providing novel insights into how the degeneration and regeneration of discrete retinal cell types is controlled.

The Johns Hopkins Center for Global NCD Research and Training consists of faculty, fellows, and students from institutions across the United States and around the globe. Our mission is to conduct high-quality research and training for the prevention and control of non-communicable diseases in low- and middle-income countries (LMIC), with an aim to build local capacity through partnerships with local institutions and communities. Our current projects encompass subject matters ranging from clean cookstoves to mental health and involve sites in Peru, Uganda, Nepal, and Bangladesh. The burden of NCDs in LMICs is growing rapidly as a result of population aging, rapid unplanned urbanization, and the globalization of unhealthy lifestyles. We envision a robust and sustainable community of NCD researchers and trainees in both high and low income settings dedicated to improving health and well-being for all.

The Todd Brown Lab focuses on metabolic, endocrine and skeletal abnormalities in HIV-infected patients, particularly as these factors relate to aging. Our studies take an epidemiologic approach to understanding the occurrence and prevalence of insulin resistance, diabetes, and anthropometric changes in HIV patients and their relationship to antiretroviral treatment.

Research in the Romsai Boonyasai Lab focuses on systems-based approaches for improving health care quality, including reducing harm during care transitions after hospital discharge and improving outcomes related to hypertension and other chronic diseases. We recently have focused on developing and evaluating practice-based tools for improving the accuracy of blood pressure measurement, overcoming clinical inertia to treatment, and engaging patients in self-management of their health.

The Swenor Research Group focuses on examining the interrelationship between vision loss and aging. This includes determining the effects of visual impairment and eye disease on physical and cognitive functioning in older adults, and identifying interventions that could enhance the health of older adults with visual impairment and eye disease.

Research in the Saowanee Ngamruengphong Lab focuses on methods for diagnosing and managing gastrointestinal conditions, including premalignant and malignant lesions of the gastrointestinal tract, esophageal cancer, colon polyps, and biliary and pancreatic disease. Our most recent work includes investigating a novel hybrid technique for closure of refractory gastrocutaneous fistula. We also conducted an international multicenter study that compared endoscopic ultrasound-guided pancreatic duct drainage with enteroscopy-assisted endoscopic retrograde pancreatography following Whipple surgery.

Shelby Kutty, M.D., Ph.D., is an authority on cardiovascular imaging, including echocardiography, 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.