Amy

Barton Pai

Dr. Barton Pai’s clinical and translational research program focuses on oxidative stress and inflammation in chronic kidney disease (CKD) patients. Her laboratory conducts in vivo and in vitro investigations of the effects intravenous iron compounds, vitamin D and other pharmaceuticals on cytokine activation, reactive oxygen species formation and lipid peroxidation to better understand the potential effects of the agents on cardiovascular and pulmonary disease in patients with kidney disease. Other research interests include pharmacokinetics and drug metabolism in CKD and effects of iron on Gram-positive organism growth and infection.

Dr. Dearborn's primary research interest is in developmental neurobiology. His research focuses on the regulation and function of the tumor suppressor vitamin-D 3 up-regulated protein 1 (VDUP1; also known as thioredoxin-interacting protein, TXNIP) in nervous system development. VDUP1 plays a critical role in the differentiation of neurons and glia, and is up-regulated under hyperglycemic conditions to trigger cell growth arrest. Importantly, VDUP1 expression, regulation, and function are evolutionarily conserved—observations founded in studies of the model organism, Drosophila . Utilizing the powerful genetic tools associated with Drosophila , Dr. Dearborn is elucidating the epistatic gene networks regulating VDUP1 expression and the role VDUP1 plays in nervous system development. This work will advance our understanding developmental neurobiology, characterize novel gene networks functioning in gliogenesis and neurogenesis, and identify new pathways underlying brain tumorigenesis.

Dr. Johnson's primary research interest is the study of inflammation-mediated organ dysfunction. His research focuses on the pathogenesis of pulmonary edema, a major cause of death and disability during systemic inflammation and septic shock. Specifically, Dr. Johnson investigates the role of the cytokine, tumor necrosis factor-a, in the pathogenesis of pulmonary edema and lung dysfunction. The effect of tumor necrosis factor-a on the lung endothelial cell cytoskeleton, protein kinase C, glycogen synthetase3 b , and reactive oxygen and nitrogen molecules is a focus in Dr. Johnson's laboratory. Recently, an additional focus in Dr. Johnson's laboratory is elucidating the pathways that link TNF-induced inflammation with neoplasia. An improved understanding of the molecular mechanisms that cause inflammation mediated organ dysfunction will ultimately lead to better treatments for septic shock and other disorders such as cancer.

Integrating his dual interests in research and patient care, his current research focuses on the epidemiology and outcomes of bacterial infections, and his work explores the antibiotic exposure-response relationship among patients. His specific objectives are 3-fold: develop patient care strategies and antibiotic regimens that improve outcomes, reduce the likelihood of toxicity, and minimize the emergence of antibiotic resistance.

This lab applies synthetic and physical organic chemistry to studies of drug design, metabolism and delivery. Current projects include the following. (1) Investigations of biological mechanisms and genetic variants which decrease the efficacy of chemotherapy. (2) The design of anticancer agents targeted to neuroblastoma, the most common, extra-cranial, solid tumor found in children. (3) For improved delivery to the brain, the design of lipophilic precursors (prodrugs) of the naturally occurring antioxidant, glutathione. The effects of aging and neurodegenerative diseases such as Alzheimer's and Parkinson's have been linked to lowered concentrations of glutathione in the brain. The use of isotopically-labeled prodrugs, in conjunction with in vivo magnetic resonance imaging (MRI), is being investigated as a non-invasive method for monitoring prodrug uptake, distribution and conversion to glutathione.

Dr. Mason’s current research interests are in vitamin D related effects in chronic kidney disease. Dr. Mason focuses his clinical and translational research efforts on vascular calcification and oxidative effects via the vitamin D receptor in vitro and in vivo through human clinical studies. Specific research goals focus on evaluating the modulation of the redox agent thioredoxin in kidney disease via the vitamin D receptor.

Dr. Pai studies strategies to optimize antimicrobial drug dosing in special populations (HIV, Cystic Fibrosis, Obesity).  This clinical translational work includes: 1) defining the in vivo and in vitro pharmacokinetic-pharmacodynamic (PK-PD) relationship of an antimicrobial; 2) translation of preclinical, Phase 1 and 2 clinical data into dosing strategies that optimize safety and efficacy.  This work has been applied to optimize dosing of generically available antifungal drugs, which are critically important to resource poor countries facing the AIDS pandemic.  His current work involves the study of the PK-PD of antimicrobials in obese patients and the effects of bariatric surgery on antimicrobial disposition.

Dr. Steiner studies the physiological strategies employed by the body to cope with infection and systemic inflammation. These host-defense strategies can be divided into two major categories. In one category are those strategies that are aimed at actively fighting infection using the body's energy reserves—fever, behavioral excitation, and hyperalgesia are typical examples of such strategies. In the other category are those strategies that are aimed at conserving the body's precious energy reserves—typical examples include hypothermia, behavioral depression, and hypoalgesia. What are the internal and environmental clues that determine which strategies are used? How does the body interpret these clues at molecular, cellular, and systemic levels? Does the body ever fail to select the most appropriate strategy? If so, are there therapeutic ways to correct for such a failure? These and other questions are currently the focus of research in Dr. Steiner's laboratory."

Dr. Zheng studies novel drug delivery systems and strategies, with a major focus on protein and peptide based biopharmaceuticals. At the same time, pharmaceutical and bioanalytical methods are developed and utilized for formulation development, drug delivery, biopharmaceutics mechanism study, stability studies and quality control. In addition, he is interested in structure-function relationships of drug targets, especially GPCRs, other membrane proteins and amyloidal proteins.