Laboratory Support Center Awardees

Robert Block MD, MPH

Assistant Professor of Epidemiology
Proposal Title: “15-epi-lipoxin in ischemic cardiomyopathy”
This is a pilot study examining the role of the antioxidant, 15-epi-lipoxin, a bioactive lipid mediator that may be associated with a cardiac protective effect in ischemic cardiomyopathy and ventricular arrhythmias. The LSC will support the genetic testing for 3 SNPs (single nucleotide polymorphisms) associated with the lipoxygenase promoter and 5-lipoxygenase activating protein. Genetic variation could impact fatty acid metabolism and indicate a risk for ventricular tachycardia, ventricular fibrillation, and sudden cardiac death.

William Bonnez MD

Associate Professor of Medicine - Infectious Diseases
Proposal Title: “Gene profiling of the variable susceptibility of human skin to infection and tumor formation by genital human papillomavirus”
This project identifies the molecular basis for susceptibility to human papillomavirus infection, which can range from benign lesions to malignant neoplasms. HPV is a major STD, with 80% of the sexually-active population being HPV exposed at some point in their lifetime. Identifying host biological factors would predict those at greatest risk for HPV infection and malignant disease.

Daniel Gray MD, PhD

Assistant Professor of Medicine - Nephrology
Proposal Title: “Towards development of a new class of potassium excreting agents ("pure kaliuretics") for treatment of hyperkalemia in chronic kidney disease”
Elevated potassium levels are potentially dangerous and can be life threatening. Normally, renal excretion handles excess potassium; however, dietary sources and ACE-inhibitors can elevate potassium into the lethal range. There is an apparent adrenal component for this regulation as adrenalectomy abolishes this regulation. This project will analyze unique blood proteins isolated from rats fed high potassium diets. Novel therapeutics can then be developed once these proteins are identified by the proteomics center (URPC).

Susan Groth, PhD, RNC, NP

Assistant Professor of Nursing
Proposal Title: “The G Protein β3 Subunit C825T Polymorphism and C/T-Haplotype Connections to Maternal/Infant Weight”
Pregnancy represents an environmental change (physiologic, hormonal, and behavioral) to the mother and identifies a time when genes can be activated/inhibited as a result of these changes. Maternal weight gain and post-pregnancy weight retention has been associated with the 825T allele of the GNB3 gene, which is important in the regulation of body fat. The 825T allele is also associated with low birth weight babies, has a high prevalence (72%) in African-American women, and, in non-pregnant carriers - is responsive to physical activity to limit weight increase. This project identifies the 825T allele in African-American mothers and the T haplotype effects on excessive maternal weight gain, post-partum weight retention, physical activity, and low birth weight.

Mesut Muyan PhD

Research Professor of Biochemistry & Biophysics, and Obstetrics & Gynecology
Proposal Title: “Identification of estrogen responsive element (ERE)-driven genes”
The objective of this project is to identify genes that are controlled by estrogen responsive elements as a therapeutic means of treating breast cancer. One third of breast cancer cases fail to respond because of loss of estrogen receptors, and other cases acquire resistance to the anti-estrogens or anti-aromatases. Using a synthesized molecule (invented by Dr Muyan) that bypasses the ERE-genes and restores estrogen receptor function, is a novel treatment strategy that could provide breast cancer treatment in cases that are otherwise resistant to therapy. The LSC will fund RT-PCR experiments that confirms data from encouraging gene array experiments conducted thus far.

Michael O'Reilly PhD

Associate Professor of Pediatrics and Environmental Medicine
Proposal Title: “Genome profiling of innate-immune privileged lung epithelial cells”
It is well known that Influenza infection targets the young and old with high morbidity and mortality. Dr O’Reilly has developed a transgenic mouse that allows for ready identification of a novel subpopulation of lung alveolar Type II cells that proliferate with Influenza exposure, but do not differentiate into Type I cells (Type II cells secrete surfactants and differentiate into Type I cells for gas exchange). This project will validate 20 genes unique to these Type II cells that have been previously identified by microarray data to have anti-microbial and anti-viral effects and other genes involved in maintaining stem cell populations. Identification of genes that control these vital lung cells will provide novel therapeutic strategies against life-threatening Influenza and other respiratory pathogens.

Anthony Pietropaoli MD

Assistant Professor of Medicine
Proposal Title: “Gender difference in long term outcome with severe sepsis”
This project is an adjunct to complement a series of other assays in a funded K23 award (Pietropaoli, PI) that identifies estrogen in reducing the morbidity and mortality in severe sepsis. Specifically, the LSC will fund the assays for determining the role of arginine metabolism: ADMA (naturally occurring NOS inhibitor) and four amino acids (arginine, ornithine, citrulline, and proline) in patients with severe sepsis.

Jay Reeder PhD & William Ricke PhD

Research Assistant Professor of Pathology & Assistant Professor of Urology
Proposal Title: “High Resolution Genotyping of Cancer Using SNP Arrays”
Bladder tumors recur in about half of all bladder cancer patients within the first two years of initial diagnosis. The high rate of recurrence necessitates life-long intensive monitoring. There is compelling evidence in the literature for clonal, oligoclonal, and multi-focal origins for recurrent bladder cancer. Using the state-of-the-art 500K SNP array analysis in the Functional Genomics Core Lab, a genome-wide SNP analysis of index and recurrent tumors would determine a clonal relationship and lay the foundation for prognosis and therapy decisions.

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Katharine Schaefer PhD

Assistant Professor of Medicine
Proposal Title: “Testing PPARγ inhibitors in a murine xenograft model”
This project examines the toxicity of PPARγ inhibitors, which have been recently identified by Dr Schaefer to have
chemotherapeutic actions on colorectal cancer, a leading cause of cancer-related deaths in the U.S. This proposal
introduces a novel treatment for colorectal cancer that could be of enormous therapeutic value, when traditional
treatment modalities are no longer effective.

Giovanni Schifitto MD

Associate Professor of Neurology
Proposal Title: “Proteomics in HIV-associated impairment”
Despite the fact that anti-HIV treatments are allowing HIV-infected patients live longer, HIV-associated cognitive impairment remains a frequent comorbidity. Using the new MALDI-TOF/TOF instrument in the proteomics center (URPC), this project will analyze 30 specific proteins induced and isolated from HIV-infected patients treated with Minocyline. Minocycline has both anti-inflammatory and neuroprotective effects and may provide treatment cues for prevention of cognitive impairment in HIV-infected patients.

R. James White MD, PhD

Assistant Professor of Medicine, Pharmacology, and Physiology
Proposal Title: “BIBT in Pulmonary Arterial Hypertension”
This project investigates whether a novel inhibitor of thrombin, BIBT 986, is effective in the treatment of pulmonary arterial hypertension (PAH), a devastating disease with few effective therapies. If BIBT 986 prevents progressive obliteration of pulmonary arterioles in rats, then this thrombin antagonist would introduce a novel treatment for PAH that could be quickly translated to humans.