Research in the Liudmila Cebotaru Lab studies cystic fibrosis transmembrane conductance regulator (CFTR) mutants. We also investigate corrector molecules that are currently in clinical trials to get a better understanding of their mechanism of action. A major focus of our research is on developing more efficient gene therapy vectors with the ultimate goal of developing a gene therapy for cystic fibrosis.

The Laboratory of Richard L. Huganir is interested in the mechanisms that regulate synaptic transmission and synaptic plasticity. Our general approach is to study molecular and cellular mechanisms that regulate neurotransmitter receptors and synapse function. We are currently focusing our efforts on the mechanisms that underlie the regulation of the glutamate receptors, the major excitatory neurotransmitter receptors in the brain.

Work in the Lewis Romer Lab focuses on the responses of vascular systems to disease and injury. Using cultured human endothelial cells and fibroblasts from mice that lack expression of the FAK- or Src-family kinases, we’re exploring several topics. These include the effect of inflammatory cytokine on cell adhesion to the extracellular matrix; the role of FAK signaling in inhibiting apoptosis; and the function of FAK- and Src-family kinases in cell-matrix interactions during adhesion and motility.

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.

Research in the Ewald laboratory starts from a simple question: Which cells in a breast tumor are the most dangerous to the patient and most responsible for metastatic disease? To answer this question, we developed novel 3-D culture assays to allow real-time analysis of invasion. Our data reveal that K14+ cancer cells play a central role in metastatic disease and suggest that the development of clinical strategies targeting these cells will provide novel breast cancer treatments.

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.

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.

David Hackam’s laboratory focuses on necrotizing enterocolitis (NEC), a devastating disease of premature infants and the leading cause of death and disability from gastrointestinal disease in newborns. The disease strikes acutely and without warning, causing sudden death of the small and large intestines. In severe cases, tiny patients with the disease are either dying or dead from overwhelming sepsis within 24 hours. Surgical treatment to remove most of the affected gut results in lifelong short gut (short bowel) syndrome. The Hackam Lab has identified a critical role for the innate immune receptor toll-like receptor 4 (TLR4) in the pathogenesis of necrotizing enterocolitis. The lab has shown that TLR4 regulates the development of the disease by tipping the balance between injury and repair in the stressed intestine of the premature infant. Developing an Artificial Intestine A key goal is to create, in the laboratory, new intestines made from patients’ own cells, which can then be implanted into the patient to restore normal digestive function. This innovative design could transform child development and quality of life in necrotizing enterocolitis survivors without the risks of conventional donor transplant.

The Miho Iijima Laboratory works to make a further connection between cells' signaling events and directional movement. Our researchers have identified 17 new PH domain-containing proteins in addition to 10 previously known genes in the Dictyostelium cDNA and genome database. Five of these genes contain both the Dbl and the PH domains, suggesting these proteins are involved in actin polymerization. A PTEN homologue has also been identified in Dictyostelium that is highly conserved with the human gene. We are disrupting all of these genes and studying their roles in chemotaxis.

The Robinson Lab studies the way in which mechanical stress guide and direct the behavior of cells, including when they are part of tissues, organs and organ systems.