The Franco D’Alessio Lab investigates key topics within the fields of critical care, internal and pulmonary medicine. We primarily explore immunological determinants of acute lung inflammation and repair. Our lab also investigates age-dependent lung immune response in patients with acute lung injury and acute respiratory distress syndrome (ARDS), regulatory T-cells in lung injury and repair, and modulation of alveolar macrophage innate immune response in ARDS.

The Frederick Anokye-Danso Lab investigates the biological pathways at work in the separation of human pluripotent stem cells into adipocytes and pancreatic beta cells. We focus in particular on determinant factors of obesity and metabolic dysfunction, such as the P72R polymorphism of p53. We also conduct research on the reprogramming of somatic cells into pluripotent stem cells using miRNAs.

The Frederick Sieber Lab studies the impact of sedation on geriatric surgical patients—especially those undergoing orthopaedic or pelvic procedures—with the goal of preventing postoperative delirium. We are using electroencephalography to investigate the effect of sedation depth during spinal anesthesia. We are also working to determine the effects of using propofol for sedation in elderly patients as well as the effects of robotics and surgical positioning on cerebral blood flow.

The studies of the Functional Neurosurgery Lab currently test whether neural activity related to the experimental vigilance and conditioned expectation toward pain can be described by interrelated networks in the brain. These two psychological dimensions play an important role in chronic pain syndromes, but their neuroscience is poorly understood. Our studies of spike trains and LFPs utilize an anatomically focused platform with high temporal resolution, which complements fMRI studies surveying the whole brain at lower resolution. This platform to analyze the oscillatory power of structures in the brain, and functional connections (interactions and synchrony and causal interactions) between these structures based upon signals recorded directly from the waking human brain during surgery for epilepsy and movement disorders, e.g. tremor. Our studies have demonstrated that behaviors related to vigilance and expectation are related to electrical signals from the cortex and subcortical structures. These projects are based upon the combined expertise of Dr. Nathan Crone in recordings and clinical management of the patients studied; Dr. Anna Korzeniewska in the analyses of signals recorded from the brain; Drs. Claudia Campbell, Luana Colloca and Rick Gracely in the clinical psychology and cognitive neurology of the expectation of pain and chronic pain; Dr. Joel Greenspan in quantitative sensory testing; and Dr. Martin Lindquist in the statistical techniques. Dr. Lenz has conducted studies of this type for more than thirty years with continuous NIH funding.

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 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.

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.

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.

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.