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Andrew Lane Lab
The Lane laboratory is focused on understanding molecular mechanisms underlying chronic rhinosinusitis and particularly the pathogenesis of nasal polyps. Diverse techniques in molecular biology, immunology, physiology, and engineering are utilized to study epithelial cell innate immunity, olfactory loss, the sinus microbiome, and drug delivery to the nose and sinus cavities. Ongoing work explores how epithelial cells participate in the immune response and contribute to chronic sinonasal inflammation. The lab creates and employs transgenic mouse models of chronic sinusitis 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 rhinovirus, and with the University of Maryland to characterize the bacterial microbiome of the nose and sinuses in health and disease.
Dr. Ross and his research team have focused on Huntington's disease and Parkinson's disease, and now are using insights from these disorders to approach more complex diseases such as schizophrenia and bipolar disorder. They use biophysical and biochemical techniques, cell models, and transgenic mouse models to understand disease processes, and to provide targets for development of rational therapeutics. These then can provide a basis for developing small molecule interventions, which can be used both as probes to study biology, and if they have favorable drug-like properties, for potential therapeutic development. We have used two strategies for identifying lead compounds. The first is the traditional path of identification of specific molecular targets, such as enzymes like the LRRK2 kinase of Parkinson’s disease. Once structure is known, computational approaches or fragment based lead discovery, in collaboration, can be used. The second is to conduct phenotypic screens using ce...ll models, or in a collaboration, natural products in a yeast model. Once a lead compound is identified, we use cell models for initial tests of compounds, then generate analogs, and take compounds that look promising to preclinical therapeutic studies in animal models. The ultimate goal is to develop therapeutic strategies that can be brought to human clinical trials, and we have pioneered in developing biomarkers and genetic testing for developing strategies. view more
Research in the Dolores Njoku Lab focuses on immune-mediated liver injury caused by drugs such as anti-seizure medications and antibiotics. We use an animal model to understand the pathways involved in the injury process, recognizing that this model can also uncover pathways involved with other drugs that cause similar liver injury. We hope to uncover the immunogenic epitopes, or pieces, of the proteins that trigger the autoimmune reaction and identify the key regulatory pathways involved.
Current projects include:
The evaluation of mechanisms of immune tolerance to cancer in mouse models of breast and pancreatic cancer. We have characterized the HER-2/neu transgenic mouse model of spontaneous mammary tumors.
This model demonstrates immune tolerance to the HER-2/neu gene product. This model is being used to better understand the mechanisms of tolerance to tumor. In addition, this model is being used to develop vaccine strategies that can overcome this tolerance and induce immunity potent enough to prevent and treat naturally developing tumors. More recently, we are using a genetic model of pancreatic cancer developed to understand the early inflammatory changes that promote cancer development.
The identification of human tumor antigens recognized by T cells. We are using a novel functional genetic approach developed in our laboratory. Human tumor specific T cells from vaccinated patients are used to identify immune relevant antigens that are chosen... based on an initial genomic screen of overexpressed gene products. Several candidate targets have been identified and the prevelence of vaccine induced immunity has been assessed .
This rapid screen to identify relevant antigenic targets will allow us to begin to dissect the mechanisms of tumor immunity induction and downregulation at the molecular level in cancer patients. More recently, we are using proteomics to identify proteins involved in pancreatic cancer development. We recently identified Annexin A2 as a molecule involved in metastases.
The analysis of antitumor immune responses in patients enrolled on vaccine studies. The focus is on breast and pancreatic cancers. We are atttempting to identify in vitro correlates of in vivo antitumor immunity induced by vaccine strategies developed in the laboratory and currently under study in the clinics. view more
Guang William Wong Lab
The Wong Lab seeks to understand mechanisms employed by cells and tissues to maintain metabolic homeostasis. We are currently addressing how adipose- and skeletal muscle-derived hormones (adipokines and myokines), discovered in our lab, regulate tissue crosstalk and signaling pathways to control energy metabolism. We use transgenic and knockout mouse models, as well as cell culture systems, to address the role of the CTRP family of hormones in physiological and disease states. We also aim to identify the receptors that mediate the biological functions of CTRPs.
Hey-Kyoung Lee Lab
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 othe...r researchers, we are analyzing various mouse models of Alzheimer's disease, especially focusing on the possible alterations in synaptic plasticity mechanisms.
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 Philip Wong Lab seeks to understand the molecular mechanisms and identification of new therapeutic targets of neurodegenerative diseases, particularly Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Taking advantage of discoveries of genes linked to these diseases (mutant APP and PS in familial AD and mutant SOD1, dynactin p150glued ALS4and ALS2 in familial ALS), our laboratory is taking a molecular/cellular approach, including transgenic, gene targeting and RNAi strategies in mice, to develop models that facilitate our understanding of pathogenesis of disease and the identification and validation of novel targets for mechanism-based therapeutics. Significantly, these mouse models are instrumental for study of disease mechanisms, as well as for design and testing of therapeutic strategies for AD and ALS.
Radiopharmaceutical Therapy and Dosimetry Lab
The Radiopharmaceutical Therapy and Dosimetry (RTD) Lab has two missions: 1. Support clinical Radiopharmaceutical Therapy (RPT) trials by performing patient-specific dosimetry and developing novel methods that advance this field and illustrate the impact of a precision medicine approach to implementing treatment planning in RPT. This includes radiobiological modeling and microscale dosimetry calculations for alpha-particle emitter RPT. 2. Pre-clinical studies using novel alpha-emitter RPT agents with immune intact transgenic animal models that incorporate modeling and dosimetry to support the translation of novel targeted radionuclide therapy strategies to the clinic. In particular, identifying how to best combine RPT with complementary orthogonal-modality agents while also obtaining a basic understanding of how the treatment works and which variables have the greatest impact on efficacy and toxicity. The underlying objective is to utilize pre-clinical modeling and dosimetry to help id...entify an optimal therapeutic clinical trial design so as to reduce unnecessary human experimentation. view more
The Reeves Lab complements genetic analyses in human beings with the creation and characterization of mouse models to understand why and how gene dosage imbalance disrupts development in Down syndrome (DS). These models then provide a basis to explore therapeutic approaches to amelioration of DS features. We use chromosome engineering in embryonic stem cells (ES) to create defined dosage imbalance in order to localize the genes contributing to these anomalies and to directly test hypotheses concerning Down syndrome "critical regions" on human chromosome 21.
Systems Biology Laboratory
The Systems Biology Lab applies methods of multiscale modeling to problems of cancer and cardiovascular disease, and examines the systems biology of angiogenesis, breast cancer and peripheral artery disease (PAD).
Using coordinated computational and experimental approaches, the lab studies the mechanisms of breast cancer tumor growth and metastasis to find ways to inhibit those processes.
We use bioinformatics to discover novel agents that affect angiogenesis and perform in vitro and in vivo experiments to test these predictions. In addition we study protein networks that determine processes of angiogenesis, arteriogenesis and inflammation in PAD. The lab also investigates drug repurposing for potential applications as stimulators of therapeutic angiogenesis, examines signal transduction pathways and builds 3D models of angiogenesis.
The lab has discovered over a hundred novel anti-angiogenic peptides, and has undertaken in vitro and in vivo studies testing their activity unde...r different conditions. We have investigated structure-activity relationship (SAR) doing point mutations and amino acid substitutions and constructed biomimetic peptides derived from their endogenous progenitors. They have demonstrated the efficacy of selected peptides in mouse models of breast, lung and brain cancers, and in age-related macular degeneration.
The Ramanathan Lab
Chronic rhinosinusitis (CRS) is a leading cause of morbidity globally and is the single most common self-reported chronic health condition and accounts for billions of dollars in health care costs and lost work days annually. Exposure to air pollutants is thought to be a critical modifier of CRS susceptibility. Despite marked reductions in air pollution levels in the United States, the fine particulate component of air pollution (PM2.5) and ultrafine pollutants secondary to traffic continue to remain a recalcitrant issue globally and in the United States. The Ramanathan Lab focuses on studying the role of air pollution (PM2.5) in CRS. In collaboration with scientists at the Bloomberg School of Public Health, we have utilized a state of the art air pollution exposure system to develop a novel mouse model of air pollution induced rhinosinusitis that mimics many of the features of CRS in humans. Our lab uses transgenic mouse models and novel immunologic/genomic techniques to study the mec...hanisms by which PM2.5 causes eosinophilic inflammation and sinonasal epithelial barrier dysfunction. We are also interested in the role of the antioxidant transcription factor, Nrf2, which has shown to stabilize the epithelial barrier and reduce eosinophilia in PM induced rhinosinusitis as a potential therapeutic target. view more