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2014 Multi-Institutional Projects

Cervical  Cancer Prevention in Louisiana

Co-Principal Investigators:
William Robinson, MD (Tulane University)
 Amber Naresh, MD, PhD (Tulane University)
Jerry McLarty, PhD (LSUHSC Shreveport)
Holiday Durham, PhD, RD, LDN (Pennington Biomedical)
Donna Williams, MPH, DrPH (LSUHSC New Orleans)
Jennifer Cameron, PhD (LSUHSC New Orleans)

With successful screening programs and appropriate implementation of the HPV vaccines, cervical cancer can be eliminated in the US.  Louisiana ranks fourth in cervical cancer incidence and third in mortality due to limited healthcare resources.  Innovative cervical cancer prevention programs that are sensitive to the unique challenges of limited-resource, health-disparate communities is hypothesized to greatly reduce cervical cancer morbidity and mortality in Louisiana. Four research projects will address this hypothesis by identifying cultural, socioeconomic and treatment factors that promote use of HPV vaccines; evaluating self-sampling with HPV testing as a primary screening alternative; identification of nutritional risk factors that promote regression of low-grade cervical intraepithelial lesions and discovery of novel molecular biomarkers that predict progression of low-grade lesions to high-grade lesions.  These efforts will combine expertise from LSU-New Orleans, LSU-Shreveport, Pennington Biomedical Research Center and Tulane University School of Medicine to reduce the impact of cervical cancer in Louisiana. 

Hydrogen  Sulfide Metabolism in Critical Limb Ischemia

Co-Principal Investigators:  
David Lefer, PhD (LSUHSC New Orleans)
Albert Sam, MD (Tulane University)

Critical limb ischemia (CLI) represents the extreme progression of peripheral artery disease (PAD) often resulting in limb loss along with a very large increase in cardiovascular mortality due to secondary events such as myocardial infarction or stroke.  Therapeutic options for CLI patients are few and largely consist of surgical revascularization and amputation. Importantly, key pathophysiological contributors to CLI remain poorly understood. Recent experimental studies indicate that the gasotransmitter hydrogen sulfide ameliorates vascular dysfunction and restores ischemic tissue perfusion, yet hydrogen sulfide bioavailability in clinical and experimental CLI remains unknown.  This application will test the hypothesis that hydrogen sulfide bioavailability is significantly decreased in CLI patients and in a large animal model of CLI.  This hypothesis will be tested through the pursuit of two aims that will: 1) measure plasma and tissue hydrogen sulfide metabolite bioavailability in CLI patients, and 2) Determine the effects of a novel H2S-donating agent (i.e., Enalapril-TBZ) in a clinically relevant swine model of Critical Limb Ischemia.  Hydrogen sulfide metabolites will be measured in clinical CLI specimens obtained from LSUHSC-Shreveport and Tulane University SOM, and the Enalapril-TBZ H2S based therapeutic study performed in a swine model of CLI.  Results from this collaborative project will establish the foundation for future clinical research and novel treatment modalities for patients with CLI.

Novel  tissue selective estrogen complex with Bazedoxifene and the prevention of  metabolic dysfunction in post-menopausal women

Co-Principal Investigator:
Eric Ravussin, PhD (Pennington Biomedical)
Frank Greenway, MD (Pennington Biomedical)

Pairing the selective estrogen receptor modulator, bazedoxifene (BZA), with conjugated estrogen (CE) as a tissue-selective estrogen complex (TSEC), is a novel menopausal therapy. Using a mouse model of post-menopausal metabolic syndrome, we recently reported that TSEC prevent estrogen deficiency-induced metabolic dysfunction without causing endometrial hyperplasia. We found that CE, BZA or TSEC increased energy expenditure and fat oxidation thus preventing obesity and glucose intolerance. Importantly, estrogens improved metabolic homeostasis by increasing production of the hormone fibroblast growth factor 21 (FGF21). A pilot cross over study under the leadership of Dr. Ravussin will translate these findings in a small cohort of six postmenopausal women. We will investigate the effect of TSEC on basal metabolic rate, fat oxidation, body composition and systemic insulin action. In parallel, under the leadership of Dr. Mauvais-Jarvis, we will continue our basic investigation using our mouse model to test the hypothesis that TSEC enhance FGF21 sensitivity.