Genetics

This research will establish prevalence data of nonalcoholic fatty liver disease (NAFLD) and the frequency of a specific indicator of genetic risk, the PNPLA3 allele, in Tucson, AZ. This project will accomplish this by assessing relationships between the PNPLA3 genotype, liver fat, and dietary behaviors in Mexican-origin adults, and evaluating the knowledge, attitudes, and beliefs of NAFLD risk, including genetic risk, held by Mexican-origin men and women. This project is funded by the American Cancer Society through its Institutional Cancer Research Center Grant. 

We are using genetics to better understand the pathophysiological intersect of type-2 diabetes and cardiovascular disease, and to better understand how and in whom statin use may lead to a higher risk of developing type-2 diabetes. This project is funded by the National Institutes of Health.  Other collaborators on this project include Alexis Frazier-Wood, Craig Stump, and Jose Ordovas. 

By identifying the genes that cause lipedema, we can determine what physiological mechanisms can be therapeutically acted upon, and we can make predictions of an individual’s risk for lipedema. A better understanding of the pathways and mechanisms underlying lipedema can thus lead to improved prevention and treatment.This project is receiving funding from The Lipedema Foundation. 

I will obtain publically available data from several studies in different ethnic/racial groups, and use data mining procedures to develop prediction models of type-2 diabetes risk from genetic markers. Career Development - This K01 grant also has a major career development component for which I am taking courses, going to workshops and conferences, and attending research seminars.

Limonene is a major component in the essential oils of citrus fruits. It has demonstrated promising breast cancer preventive and therapeutic effects in preclinical model systems. This goal of this study is to evaluate the distribution of limonene to the breast tissue and its associated biological activities after 2 to 6 weeks of limonene dosing in women with a recent diagnosis of breast carcinoma in situ or atypical ductal hyperplasia scheduled to undergo definitive surgery by conducting an early phase clinical trial. This study will help evaluate the potentials of developing limonene as a breast cancer preventive agent. The long-term goals are to conduct long-term intervention trials to determine the breast cancer preventive activity of d-limonene and to conduct translational clinical research in understanding the effect of d-limonene on arresting/inhibiting/reversing the breast cancer carcinogenesis process. This project was funded by the National Institutes of Health.

Low relative skeletal muscle mass (SMM) or sarcopenia significantly contributes to the decline in physical functioning among the elderly. Very little is known about genetic risk factors and their interactions with environmental factors in aging-related SMM loss. There are some indications that inflammatory factors and reduced levels of anabolic hormones are associated with lower muscle mass. These associations need to be confirmed in larger prospective studies and the exact role of each identified biomarker in the development of sarcopenia remains to be investigated. Since physical function impairment and disability are more prevalent in women than in men during later life, it is especially important to understand the mechanisms of muscle loss and to prevent sarcopenia among older women. The primary objective of this study is to identify genetic factors and biomarkers that are relevant to low SMM and high rates of SMM loss in older women. We will achieve two specific aims: Assess the association of cytokines and hormonal factors with low SMM and the rate of SMM loss, and Evaluate the role of genetic variation in catabolic inflammatory cytokines (IL-6, IL-1, TNF-alpha) as well as in anabolic growth factors (IGF1, Growth Hormone) related to SMM and the rate of SMM loss in a large cohort of Hispanic and non-Hispanic White postmenopausal women. Study participants will come from the Women's Health Initiative Observational Study. All of these women have had repeat body composition measurements by using Dual-energy X-ray Absorptiometry (DXA) during the nine- year follow-up. Their SMM will be assessed using a DXA-derived method developed by this research team. Genetic variations in selected catabolic (e.g.IL-1, IL6, TNF-a) as well as anabolic (e.g. IGF-1, and GH) factors will be assessed for the entire sample (n = 2800). Analyses of biomarkers, including IL-6, TNF-a, adiponectin, C-reactive protein, IL-1ra, IL-6sR, TNF Rll, acid labile subunitJGF-1, and IGFBP-3, will be conducted among 50 percent of the participants in this study. Regression and mixed effects models will be used in the final data analysis. This study is unique and innovative in the study design, selection of bioassays, and the study population. Results of this study will have significant impacts on the prevention and reduction of adverse health outcomes associated with sarcopenia of older women in the United States. This project was funded by National Institute on Aging of the National Institutes of Health. 

Subcontract of ARRA Prime Award with Vanderbilt University.  Bonnie LaFleur was a contributor on this project but has since left the University of Arizona.

This project was designed to investigate the role of vitamin D and genetic differences in the Vitamin D pathway on the develop of the precursor to colon cancer. The research team is using combined approaches from epidemiology and molecular biology to study functional changes and the pathway and their effects on colorectal carcinogenesis. Project funding came from the National Cancer Institute. 

Epidemiological and laboratory research has shown that dietary intake of vitamin D and calcium may be associated with a decreased risk of colorectal neoplasia, and that polymorphisms of the vitamin D receptor (VDR) may also be associated with risk. In addition, it was reported that the potentially carcinogenic bile acid lithocholic acid (LCA) is a ligand for the VDR. The effects of LCA-VDR binding on colorectal neoplasia are unknown. Therefore, we conducted a study to investigate whether VDR polymorphisms are associated with the risk of colorectal adenoma recurrence and whether this association is modified by dietary intake of vitamin D, calcium, and fat. The combination of two study populations from separate nutrition intervention trials provided us with approximately 2500 participants and allowed us to perform the largest epidemiological study of this kind to date. In addition, we had the ability to conduct experiments in molecular biology to test the functional role of the VDR in colorectal neoplasia , including the translational effects of VDR polymorphisms and LCA binding in colon cancer cell lines. Completion of these objectives required thorough and detailed training in epidemiological design and analysis, statistical analyses of gene-nutrient interactions, and molecular approaches to laboratory experimentation. The sponsor for this proposal and project, Dr. David Alberts, and cosponsors, Dr. Mark Haussler, Dr. Elena Martinez, and Dr. Sylvan Green provided expertise, guidance, and support for the successful completion of the proposed research along with the Arizona Cancer Center (ACC) at the University of Arizona. This project was funded by the National Institutes of Health.