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 under 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.

Our lab is focused on using comprehensive gene expression, methylation and sequencing and metabolomics analysis to identify alterations in breast cancer, and exploiting these for early detection and therapy. Among deferentially expressed genes, our lab has focused on the HOX genes. HOX genes are intimately involved in the development of resistance to both chemotherapy and to agents targeting the estrogen receptor. Our work explores the alternate pathways that are activated by HOX proteins leading to this resistance and novel treatments to overcome resistance in both tissue culture and xenograft models. In addition, epigenetically silenced genes and a metabolic reprogramming in tumors also trigger novel early detection and therapeutic strategies. We are testing the utility of differentiation therapy through reactivating RAR-beta in breast cancer using histone deacetylase inhibitors with great success. Also, we are targeting enzymes involved in gluconeogenesis and glycolysis with small molecule FDA-approved antimetabolites to achieve antitumor effects.

The Robert Wise Lab conducts clinical trials to study chronic obstructive lung diseases (COPD). We investigate inhaled corticosteroids in patients with mild to moderate COPD and the effectiveness of anti-inflammatories in allowing lung growth in mild to moderate asthmatic children. Our research includes exploring the efficacy of various treatments for asthmatic women who are pregnant and of lung-volume reduction surgery for emphysema patients. We also conduct studies of the clinical epidemiology, pathobiology and treatment of interstitial lung disease in patients with scleroderma.

The Systems neurobiology Laboratory is a group of laboratories that all study various aspects of neurobiology. These laboratories include: (1) computational neurobiology Laboratory: The goal of their research is to build bridges between brain levels from the biophysical properties of synapses to the function of neural systems. (2) computational Principles of Natural Sensory Processing: Research in this lab focuses on the computational principles of how the brain processes information. (3) Laboratory for Cognitive neuroscience: This laboratory studies the neural and genetic underpinnings of language and cognition. (4) Sloan-Swartz Center for Theoretical neurobiology: The goal of this laboratory is develop a theoretical infrastructure for modern experimental neurobiology. (5) Organization and development of visual cortex: This laboratory is studying the organization and function of neural circuits in the visual cortex to understand how specific neural components enable visual perception and to elucidate the basic neural mechanisms that underlie cortical function. (6) Neural mechanism of selective visual attention: This laboratory studies the neural mechanisms of selective visual attention at the level of the individual neuron and cortical circuit, and relates these findings to perception and conscious awareness. (7) Neural basis of vision: This laboratory studies how sensory signals in the brain become integrated to form neuronal representation of the objects that people see.

Investigators in the Roger Johns Lab are examining the molecular mechanisms behind the onset and continuation of chronic pain, particularly neuropathic pain. This work has led to a better understanding of the vast network of molecules at neuronal synapses, particularly the postsynaptic density (PSD), which is key to the propagation of pain signals. We're working to develop new analgesics that interfere with the PSD protein interactions in an effort to better treat patients who suffer from chronic pain.

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 mechanisms 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.

Research in the Richard Chaisson Lab primarily examines tuberculosis and HIV infection, with specific focus on global epidemiology, clinical trials, diagnostics and public health interventions. Our recent research has involved evaluating a molecular diagnostic test for tuberculosis in HIV patients; observing TB responses during treatment of pulmonary tuberculosis; and examining antiretroviral therapy adherence, virologic and immunologic outcomes in adolescents compared with adults in Southern Africa.

The key research interests in the Robert Bollinger Lab include identifying biological and behavioral risk factors for HIV transmission as well as characterizing the clinical progression and treatment of HIV and related infectious diseases. We also have a long-standing interest in optimizing health care capacity and delivery in settings with limited resources. Our work includes implementing science research projects to explore the effectiveness of initiatives such as task-shifting, clinical education, distance learning and mobile health programs as a way to improve health care in these locations.

Work in the Robert H. Brown Lab explores several topics within pulmonary physiology, with a long-term goal of understanding the structural changes in the lungs that lead to the pathophysiology of lung disease. Our core studies examine the structure-function relationship of pulmonary airways and vessels as well as their role in chronic obstructive pulmonary disease (COPD) and reactive airway disease. Recent research has involved studying the mechanisms and treatment of COPD progression, new methods for treating asthma, and lung inflation and airway hyperresponsiveness. We are also exploring the impact of HIV infection on the etiology of lung disease and the pathophysiologic consequences of lung distention.

The Roy Brower Lab conducts clinical trials related to the management of acute respiratory distress syndrome (ARDS). Our research also involves oxygen toxicity, a potentially fatal condition caused by too much supplemental oxygen.