Our lab is focused on determining the role of hypoxia in breast cancer metastasis. We are particularly interested in the changes in the extracellular matrix that occur under hypoxic conditions and promote cancer cell migration.

The Bigos Lab focuses on a Precision Medicine approach to the treatment of psychiatric illness. In addition, this lab employs functional neuroimaging and genetics as biomarkers in neuropsychiatric drug development. A recent study used functional MRI to test the neural effects of a drug with the potential to treat cognitive dysfunction in schizophrenia. Other studies aim to identify patient-specific variables including sex, race, and genetics that impact drug clearance and clinical response to better select and dose antipsychotics and antidepressants.

The Dara Kraitchman Laboratory focuses on non-invasive imaging and minimally invasive treatment of cardiovascular disease. Our laboratory is actively involved in developing new methods to image myocardial function and perfusion using MRI. Current research interests are aimed at determining the optimal timing and method of the administration of mesenchymal stem cells to regenerate infarcted myocardium using non-invasive MR fluoroscopic delivery and imaging. MRI and radiolabeling techniques include novel MR and radiotracer stem cell labeling methods to determine the location, quantity and biodistribution of stem cells after delivery as well as to noninvasively determine the efficacy of these therapies in acute myocardial infarction and peripheral arterial disease. Our other research focuses on the development of new animal models of human disease for noninvasive imaging studies and the development of promising new therapies in clinical trials for companion animals.

Dr. Bhujwalla’s lab promotes preclinical and clinical multimodal imaging applications to understand and effectively treat cancer. The lab’s work is dedicated to the applications of molecular imaging to understand cancer and the tumor environment. Significant research contributions include 1) developing ‘theranostic agents’ for image-guided targeting of cancer, including effective delivery of siRNA in combination with a prodrug enzyme 2) understanding the role of inflammation and cyclooxygenase-2 (COX-2) in cancer using molecular and functional imaging 3) developing noninvasive imaging techniques to detect COX-2 expressing in tumors 4) understanding the role of hypoxia and choline pathways to reduce the stem-like breast cancer cell burden in tumors 5) using molecular and functional imaging to understand the role of the tumor microenvironment including the extracellular matrix, hypoxia, vascularization, and choline phospholipid metabolism in prostate and breast cancer invasion and metastasis, with the ultimate goal of preventing cancer metastasis and 6) molecular and functional imaging characterization of cancer-induced cachexia to understand the cachexia-cascade and identify novel targets in the treatment of this condition.

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.

In the Lee Martin Laboratory, we are testing the hypothesis that selective vulnerability--the phenomenon in which only certain groups of neurons degenerate in adult onset neurological disorders like amyotrophic lateral sclerosis and Alzheimer's disease--is dictated by brain regional connectivity, mitochondrial function and oxidative stress. We believe it is mediated by excitotoxic cell death resulting from abnormalities in excitatory glutamatergic signal transduction pathways, including glutamate transporters and glutamate receptors as well as their downstream intracellular signaling molecules. We are also investigating the contribution of neuronal/glial apoptosis and necrosis as cell death pathways in animal (including transgenic mice) models of acute and progressive neurodegeneration. We use a variety of anatomical and molecular neurobiological approaches, including neuronal tract-tracing techniques, immunocytochemistry, immunoblotting, antipeptide antibody production, transmission electron microscopy and DNA analysis to determine the precise regional and cellular vulnerabilities and the synaptic and molecular mechanisms that result in selective neuronal degeneration.

Research in the Nicola Heller Lab focuses on the immunobiology of macrophages. Our team explores how these cells impact diseases with an inflammatory element, such as cancer, cardiovascular disease and obesity. Using a variety of techniques, including molecular and cellular biology, biochemistry, mouse models and more, we study the role of IL-4/IL-13 signaling in asthma and allergic disease, as well as the role of alternatively activated macrophages (AAM) in the pathogenesis of allergic inflammation. Currently, we are researching the links between asthma and obesity, with a focus on the roles of gender and race.

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.

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.

Research in the Meredith McCormack Lab deals primarily with pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and the role of environmental exposures in lung diseases. We have researched the factors that contribute to inner-city asthma, with a focus on how particulate matter air pollution impacts pulmonary function. We are also part of the LIBERATE clinical study, which is focused on patients who experience difficulty breathing and have been diagnosed with severe emphysema. We also have a longstanding interest in the effects of race/ethnicity, poverty and urbanization on nutrition and food allergies.