Investigators in the IBD and Autoimmune Liver Diseases Laboratory conduct basic and translational research in inflammatory bowel disease (IBD) and autoimmune liver diseases. One area of focus is discovering and developing biomarkers for diagnosing and prognosticating IBD and other autoimmune liver diseases (AILDs). We also are exploring the molecular pathogenesis of—and developing novel therapies for—IBD. In addition, we are working to understand the molecular reason why many IBD patients fail to respond to mainstay drug therapies—and to develop diagnostic assays that can predict non-responders before starting them on those therapies. These biomarker studies have led to our application for four U.S. and international patents.

Led by Stephen Wegener, Ph.D, this research group focuses on projects that have the potential to improve function and quality of life and reduce disability following injury or illness. These projects include research on cognitive, behavioral, psychological and health care system factors that affect outcomes following injury.

Our IndoUS team, based both in Baltimore and in India, specializes in international clinical research (cohort studies and clinical trials), public health implementation science and education in infectious diseases, HIV/AIDS, tuberculosis (TB), vaccine preventable illnesses, antimicrobial resistant infections, and more recently COVID. Since 2003, our work has been focused primarily on India, where we are engaged in several Indo-JHU and international research collaborations. We partner with several leading medical and research institutions in India (e.g. BJGMC, DY Patil, Hinduja Hospital, KEM, Bharati Vidyapeeth, NIRT, JIPMER, CMC, Medanta, IISER, YRG, IIT), as well as others in sub-Saharan Africa, US and Brazil. We are actively involved in the following consortia: 1) Indo-US Vaccine Action Program sponsored RePORT India TB research consortium, which is funded by the US National Institutes of Health (NIH) and the government of India, Department of Biotechnology. 2) RePORT International TB Research Consortium, a multilateral global consortia for TB research, 3) US NIH funded multi-country HIV and TB trials consortia of the AIDS Clinical Trials Group (ACTG) and the International Maternal Pediatric Adolescent AIDS Trials Network (IMPAACT) Network, 4) NIH and AmFAR funded IeDea HIV/TB Working Group and the Treat Asia-IeDEA HIV and TB epidemiology databases, and 5) CDC SHEPHERD AMR studies. Our group has been awarded research grants from the US NIH, US CDC, UNITAID, Indian government, and several philanthropic foundations to investigate infectious diseases of importance to India and beyond.

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 International Arts + Mind Lab (IAM Lab) Center for Applied Neuroaesthetics is a multidisciplinary research-to-practice initiative at Johns Hopkins University that is accelerating the field of neuroarts through the study of neuroaesthetics. The lab brings together brain scientists and practitioners in the visual and performing arts, architecture and design, and creative arts therapies to foster collaboration and research. 

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.

Intestinal chloride secretion is stimulated during diarrhea. Cholera toxin is secreted by bacterium Vibrio cholera and is responsible for the watery diarrhea after cholera infection. Mechanistically, cholera toxin increases intracellular cyclic AMP, which subsequently activates protein kinase A and the cystic fibrosis transmembrane regulator chloride channel (CFTR). However, we recently identified an intestinal cAMP-Ca cross-talk signaling pathway that is initiated by elevation of intracellular cAMP and subsequently elevates intracellular Ca concentrations through the exchange protein activated by cAMP (Epac). This observation suggests that both CFTR and calcium-activated chloride channels are targets of elevated intracellular cAMP signaling molecule. Therefore, we are studying the role of calcium-activated Cl channels in intestinal chloride secretion under physiological conditions and during diarrhea. We are also determining whether the recently identified transmembrane protein 16 family of proteins, which are calcium-activated chloride channels, is also involved in intestinal chloride secretion in addition to the well characterized CFTR channel. Increased understanding of regulation of intestinal Cl secretion provides the necessary background information for the development of therapeutic drugs for the treatment of diarrhea, constipation and cystic fibrosis. The discovery that calcium-activated chloride channels are involved in intestinal chloride secretion provides additional targets for anti-diarrhea drug development.

Secretory diarrhea is a leading cause of childhood morbidity and mortality in developing countries. While diarrhea can be treated with oral rehydration solution (ORS), inclusion of zinc with oral ORS has been shown to reduce the duration of diarrhea. However, how zinc improves diarrhea is not known. It has been shown that zinc acts as an intestinal epithelial cell basolateral potassium channel blocker of cyclic AMP-mediated chloride secretion. We discovered that zinc also stimulates intestinal sodium and water absorption via the epithelial Na/H exchanger, NHE3. Zinc reverses the effect of cyclic AMP inhibition of NHE3 activity. The effect of zinc on NHE3 cannot be duplicated with other divalent metal ions. It has been well established that Na/H exchanger regulatory proteins are involved in NHE3 regulation. Whether these regulatory proteins are involved in zinc stimulation of NHE3 is a focus of our study. Our goal is to reveal mechanisms to explain how zinc improves diarrhea and to understand the role of zinc in salt and water homeostasis in the gut. Our study will provide a scientific basis to justify the inclusion of zinc in ORS for the treatment of secretory diarrhea.

The In-vivo Cellular and Molecular Imaging Center conducts multidisciplinary research on cellular and molecular imaging related to cancer. We provide resources, such as consultation on biostatistics and bioinformatics and optical imaging and probe development, to understand and effectively treat cancer. Our molecular oncology experts consult on preclinical studies, use of human tissues, interpretation of data and molecular characterization of cells and tumor tissue.

Research in the Ivor Berkowitz Lab targets pediatric critical care medicine. We are particularly interested in the pathophysiology behind the cerebrovascular dysfunction that occurs in bacterial meningitis as well as the anesthetic and perioperative complications of patients with dwarfing syndromes.