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 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.

Research in the Michael Matunis Lab focuses on the SUMO family of small ubiquitin-related proteins. We study the covalent conjugation of SUMOs to other cellular proteins, which regulates numerous processes needed for cell growth and differentiation, and which, when defective, can lead to conditions such as cancer, neurodegenerative disease and diabetes.

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.

Our research aims to expand the understanding of how hormones regulate pancreatic islets in health and disease. Currently, a major focus of the lab is to define the normal adaptations of islets, particularly insulin-producing beta-cells, to the metabolic stress of pregnancy, and to determine how defective adaptation contributes to gestational diabetes mellitus (GDM). We anticipate that elucidating physiologic mechanisms of gestational beta-cell adaptation will identify novel therapeutic strategies to expand functional beta-cell mass which would help in the treatment of all types of diabetes.

The Ronald Schnaar Lab is involved in the rapidly expanding field of glycobiology, which studies cell surface glycans, lectins, and their roles in cell physiology. Current projects in our lab study include (1) Glycans and glycan-binding proteins in inflammatory lung diseases, (2) Ganglioside function in the brain, and (3) HIV-Tat and HIV-associated neurocognitive disorders.

The research in the Svetlana Lutsenko Laboratory is focused on the molecular mechanisms that regulate copper concentration in normal and diseased human cells. To understand the molecular mechanisms of copper homeostasis in normal and diseased human cells, we utilize a multidisciplinary approach involving biochemical and biophysical studies of molecules involved in copper transport, cell biological studies of copper signaling, and analysis of copper-induced pathologies using Wilson's disease gene knock-out mice.

Research in the Shigeki Watanabe Lab focuses on the cellular and molecular characterizations of rapid changes that occur during synaptic plasticity. Our team is working to determine the composition and distribution of proteins and lipids in the synapse as well as understand how the activity alters their distribution. Ultimately, we seek to discover how the misregulation of protein and lipid compositions lead to synaptic dysfunction. Our studies make use of cutting-edge electron microscopy techniques in combination with biochemical and molecular approaches.

The research in the Sarbjit Saini Laboratory focuses on IgE receptor biology and IgE receptor-mediated activation of blood basophils and mast cells. We have examined the role of IgE receptor expression and activation in allergic airways disease, anaphylaxis and chronic urticaria. Our research has been supported by the NIH, American Lung Association and the AAAAI. Our current research interests have focused mechanisms of diease in allergic asthma, allergic rhinitis and also translational studies in chronic idiopathic urticaria.

The Lane laboratory is focused on understanding molecular mechanisms underlying chronic rhinosinusitis, particularly the pathogenesis of nasal polyps, as well as inflammation on the olfactory epithelium. Diverse techniques in molecular biology, immunology, and physiology are utilized to study epithelial cell innate immunity, olfactory loss, and response to viral infection. Ongoing work explores how epithelial cells of the sinuses and olfactory mucosa participate in the immune response and contribute to chronic inflammation. The lab creates and employs transgenic mouse models of chronic nasal/sinus inflammation to support research in this area. Collaborations are in place with the School of Public Health to explore mechanisms of anti-viral immunity in influenza and COVID-19.