The Mihaela Pertea Lab develops computational tools for RNA sequence analysis, gene finding, splice-site prediction and sequence-motif finding. Previous research projects led to the development of open-source software systems related to finding genes.

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 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.

HPTN (HIV Prevention Trials Network) Network Laboratory (NL) is responsible for collecting, testing and reporting results from biological samples; assisting in the development and quality assurance assessment of local laboratory capacity at the Clinical Trials Units (CTUs) participating in HPTN clinical trials (www.hptn.org); and identifying and implementing state-of-the-art assays and technologies to advance the scientific agenda of the Network.

The Theresa Shapiro Laboratory studies antiparasitic chemotherapy. On a molecular basis, we are interested in understanding the mechanism of action for existing antiparasitic agents, and in identifying vulnerable metabolic targets for much-needed, new, antiparasitic chemotherapy. Clinically, our studies are directed toward an evaluation, in humans, of the efficacy, pharmacokinetics, metabolism and safety of experimental antiparasitic drugs.

The O'Connor Lab studies the molecular basis of infectious disease using Legionella pneumophila pathogenesis as a model system. We are looking at the network of molecular interactions acting at the host-pathogen interface. Specifically, we use L. pneumophila pathogenesis to examine the numerous mechanisms by which an intracellular bacterial pathogen can establish infection, how it exploits host cell machinery to accomplish this, and how individual proteins and their component pathways coordinately contribute to disease. We are also studying the role of environmental hosts in the evolution of human pathogens. Using genetics and functional genomics, we compare and contrast the repertoires of virulence proteins required for growth in a broad assortment of hosts, how the network of molecular interactions differs between hosts, and the mechanisms by which L. pneumophila copes with this variation.

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 Rao Laboratory studies the roles of intracellular cation transport in human health and disease using yeast as a model organism. Focus areas include intracellular Na+(K+)/H+ exchange and Golgi CA2+(MN+) ATPases.

The Richard Rivers Lab researches vascular communication with a focus on microcirculation physiology. Our team seeks to determine how metabolic demands are passed between tissue and the vascular network as well as along the vascular network itself. Our goal is to better understand processes of diseases such as cancer and diabetes, which could lead to the development of more targeted drugs and treatment. We are also working to determine the role for inwardly rectifying potassium channels (Kir) 2.1 and 6.1 in signaling along the vessel wall as well as the role of gap junctions.

The research in the Svetlana Lutsenko Laboratory is focused on the molecular mechanisms that regulate copper concentration in normal and diseased human cells. Copper is essential for human cell homeostasis. It is required for embryonic development and neuronal function, and the disruption of copper transport in human cells results in severe multisystem disorders, such as Menkes disease and Wilson's disease. 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.