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.

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.

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.

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.

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.

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.

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 Hoffmann Lab is focused on reducing TB and HIV morbidity and mortality in the low and middle income settings through behavioral and implementation science approaches. Work has focused on understanding individual-level behavior towards linkage to care and continued care engagement for HIV and TB and using this knowledge to develop approaches to increase HIV testing, linkage to care, HIV viral load suppression, and retention in care. Other work has focused on health system strategies to improve service delivery and improve adherence to best practice to guidelines-based care. The group's research includes work on the general population, corrections inmates and ex-inmates, men at risk for HIV, and recently hospitalized individuals. Most of the research has been in South Africa and elsewhere in sub-Saharan Africa.

The Hey-Kyoung Lee Lab is interested in exploring the cellular and molecular changes that happen at synapses to allow memory storage. We use various techniques, including electrophysiological recording, biochemical and molecular analysis, and imaging, to understand the cellular and molecular changes that happen during synaptic plasticity. Currently, we are examining the molecular and cellular mechanisms of global homeostatic synaptic plasticity using sensory cortices as model systems. In particular, we found that loss of vision elicits global changes in excitatory synaptic transmission in the primary visual cortex. Vision loss also triggers specific synaptic changes in other primary sensory cortices, which we postulate underlies sensory compensation in the blind. One of our main research goals is to understand the mechanisms underlying such cross-modal synaptic plasticity. We are also interested in elucidating the events that occur in diseased brains. In collaboration with other researchers, we are analyzing various mouse models of Alzheimer's disease, especially focusing on the possible alterations in synaptic plasticity mechanisms.

The Brain Health Program is a multidisciplinary team of faculty from the departments of neurology, psychiatry, epidemiology, and radiology lead by Leah Rubin and Jennifer Coughlin. In the hope of revealing new directions for therapies, the group studies molecular biomarkers identified from tissue and brain imaging that are associated with memory problems related to HIV infection, aging, dementia, mental illness and traumatic brain injury. The team seeks to advance policies and practices to optimize brain health in vulnerable populations while destigmatizing these brain disorders. Current and future projects include research on: the roles of the stress response, glucocorticoids, and inflammation in conditions that affect memory and the related factors that make people protected or or vulnerable to memory decline; new mobile apps that use iPads to improve our detection of memory deficits; clinical trials looking at short-term effects of low dose hydrocortisone and randomized to 28 days of treatment; imaging brain injury and repair in NFL players to guide players and the game; and the role of inflammation in memory deterioration in healthy aging, patients with HIV, and other neurodegenerative conditions.