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.

The Fukunaga Lab uses multidisciplinary approaches to understand the cell biology, biogenesis and function of RNA-binding proteins and small silencing RNAs from the atomic to the organismal level. The lab studies (1) biology and molecular functions and mechanisms of uncharacterized RNA-binding proteins, and (2) how small silencing RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs), are produced and function. Mutations in the RNA-binding protein and small RNA genes cause many diseases, including cancers. We use a combination of biochemistry, Drosophila genetics, molecular biology, cell culture, and next-generation sequencing, to answer fundamental biological questions and also potentially lead to therapeutic applications to human diseases.

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 identify an optimal therapeutic clinical trial design so as to reduce unnecessary human experimentation.

Research in the Rahul Koka Lab focuses on pediatric airways, patient safety and health disparities. Recent studies have focused on the relationship between socioeconomic status and perioperative outcomes and patient safety factors related to interoperative cardiac arrests. We also performed effects analyses of the maintenance and repair of anesthetic equipment in various medical environments.

Research in the Rasika Mathias Lab focuses on the genetics of asthma in people of African ancestry. Our work led to the first genomewide association study of its kind in 2009. Currently, we are analyzing the whole-genome sequence of more than 1,000 people of African ancestry from the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA). CAAPA’s goal is to use whole-genome sequencing to expand our understanding of how genetic variants affect asthma risk in populations of African ancestry and to provide a public catalog of genetic variation for the scientific community. We’re also involved in the study of coronary artery disease though the GeneSTAR Program, which aims to identify mechanisms of atherogenic vascular diseases and attendant comorbidities.

The Retinal Cell and Molecular Laboratory has three major areas of interest, each of which deals with some aspect of growth factor signaling and function in the retina and retinal pigmented epithelium (RPE): 1. Investigations aimed at gaining a better understanding of the pathogenesis of retinal and choroidal neovascularization and developing new ways to treat them. 2. Investigations aimed at understanding the molecular signals involved in retinal and RPE wound repair and scarring. The prototypical disease in this category is proliferative vitreoretinopathy and our laboratory is seeking to identify new treatments for it. 3. Investigations aimed at understanding why retinal degenerations occur and how they might be treated, with particular emphasis on neurotrophic factors.

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.

Research in the Robert Siliciano Laboratory focuses on HIV and antiretroviral therapy (ART). ART consists of combinations of three drugs that inhibit specific steps in the virus life cycle. Though linked to reduced morbidity and mortality rates, ART is not curative. Through our research related to latently infected cells, we've shown that eradicating HIV-1 infection with ART alone is impossible due to the latent reservoir for HIV-1 in resting CD4+ T cells. Our laboratory characterized the different forms of HIV-1 that persist in patients on ART. Currently, we are searching for and evaluating drugs that target the latent reservoir. We are also developing assays that can be used to monitor the elimination of this reservoir. We are also interested in the basic pharmacodynamic principles that explain how antiretroviral drugs work. We have recently discovered why certain classes of antiretroviral drugs are so effective at inhibiting viral replication. We are using this discovery along with experimental and computational approaches to develop improved therapies for HIV-1 infection and to understand and prevent drug resistance. Finally, we are studying the immunology of HIV-1 infection, and in particular, the ability of some patients to control the infection without ART.

Research in the Raymond Koehler Lab explores cerebrovascular physiology and cerebral ischemic injury caused by stroke and cardiac arrest, using protein analysis, immunohistochemistry and histology. We also study ischemic preconditioning, neonatal hypoxic-ischemic encephalopathy and the mechanisms of abnormal cerebrovascular reactivity after ischemia. We 're examining ways to improve tissue oxygenation and seek to better understand the mechanisms that connect an increase in cerebral blood flow to neuronal activity.