Every 40 seconds, someone in the U.S. has a heart attack. In even less time, another person is diagnosed with cancer. Nearly all of us have been impacted by these diseases, yet their origins are not fully understood. It is because cardiovascular disease, cancer, and other common conditions are highly complex; a person’s genetics, age, and lifestyle factors, such as diet and exercise, all play a role. Great efforts are needed to unravel these networks to understand complex diseases and how to better treat them. To do our part in addressing this monumental challenge, our creative and vibrant team is using innovative technologies to pinpoint the genes responsible for complex diseases and determine how those genes interact with age, diet and other factors that drive disease onset. In the coming years, our discoveries will support early identification of patients at risk for particular complex diseases and inspire the development of more effective therapies, leading to a brighter, healthier future for us all.
Our Current Research Projects
Defining the Genetic Architecture of the Glutathione Redox System (PI: Robert Pazdro)
Robert Pazdro, Rebecca Gould, and Steven Craig
We will address the following specific aims: 1) to quantify the heritability of core GSH phenotypes in a genetically diverse population; 2) to define genomic regions associated with the GSH system, and delineate shared and tissue-specific loci; and 3) to prioritize candidate genes, and initiate functional analyses of the most compelling candidates. These studies will define the fundamental genetic architecture of an indispensable biochemical system that governs cellular stress resistance and survival. Knowledge gained from these efforts will inform a series of future clinical and mechanistic studies aimed at understanding the impact of GSH genes on cellular damage during stress, and the data will build a foundation for innovative therapies to maintain tissue integrity in patients with degenerative diseases, thereby increasing their health spans and improving their qualities of life.
R01 GM121551 National Institutes of Health/National Institute of General Medical Sciences
A Systems Approach to GDF11 and its Effects on Cardiac Hypertrophy (PI: Robert Pazdro)
Robert Pazdro and Kristen Peissig
Our overarching hypothesis predicts that the GDF11 paradigm, wherein changes in GDF11 levels drive age-related cardiac hypertrophy, is strongly influenced by genetic factors. To test that hypothesis, we will use the revolutionary Diversity Outbred (DO) stock, and its eight founder strains, to address the following specific aims: 1) To validate the relationship between GDF11 and cardiac hypertrophy, and to test whether the relationship is dependent on genetic background; and 2) To define the genetic architecture of GDF11 levels using the DO, and to contrast the results against the genes that underlie cardiac hypertrophy. For each aim, we will use mass spectrometry to distinguish and quantify GDF11 and myostatin, enabling us to unambiguously differentiate between these proteins and to characterize the unique effects of GDF11 on age-related cardiac hypertrophy. These studies will reveal the underlying genetic contributors to circulating GDF11 levels, and the identification of novel genes will add critical and fresh insights into the fundamental biological pathways that couple advanced age and cardiac hypertrophy. Knowledge gained from these efforts will directly contribute to the ultimate goal of developing effective treatment strategies against age-related cardiovascular disease.
R56 AG053309 National Institutes of Health/National Institute on Aging
Santos TSd, Teng PY, Yadav S, Castro FLdS, Gould RL, Craig SW, Chen C, Fuller AL, Pazdro R, Sartori JR, and Kim WK. Effects of Inorganic Zn and Cu Supplementation on Gut Health in Broiler Chickens Challenged With Eimeria spp. Front Vet Sci. 2020 Apr. doi: 10.3389/fvets.2020.00230.
Gould RL and Pazdro R. Impact of supplementary amino acids, micronutrients, and overall diet on glutathione homeostasis. Nutrients. 2019;11(5):1056.
Gould RL, Zhou Y, Yakaitis CL, Love K, Reeves J, Kong W, Coe E, Xiao Y, and Pazdro R. Heritability of the aged glutathione phenotype is dependent on tissue of origin. Mamm Genome. 2018;29(9-10):619-31.
Bumgardner SA, Zhou Y, Jiang Z, Coe EJ, Yakaitis CL, Xiao Y, and Pazdro R. Genetic influence on splenic natural killer cell frequencies and maturation among aged mice. Experimental Gerontology 2018; 104: 9-16.
Norris KM, Okie W, Kim WK, Adhikary R, Yoo S, King S, and Pazdro R. A high-fat diet differentially regulates glutathione phenotypes in the obesity-prone mouse strains DBA/2J, C57BL/6J, and AKR/J. Nutrition Research 2016; 36: 1316-1324.
Norris KM, Okie W, Yakaitis CL, and Pazdro R. The anthocyanin cyanidin-3-O-beta-glucoside modulates murine glutathione homeostasis in a manner dependent on genetic background. Redox Biology 2016; 9:254-263.
Jiang Z, Harrison DE, Parsons ME, McClatchy S, Jacobs L, and Pazdro R. Heritability of in vitro phenotypes exhibited by murine adipose-derived stromal cells. Mammalian Genome 2016; 27(9-10): 460-468.
Zhou Y, Jiang Z, Harris EC, Reeves J, Chen X, and Pazdro R. Circulating concentrations of growth differentiation factor 11 are heritable and correlate with life span. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2016; 71:1560-1563.
Zhou Y, Harrison DE, Love-Myers K, Chen Y, Grider A, Wickwire K, Burgess JR, Stochelski MA, and Pazdro R. Genetic analysis of tissue glutathione concentrations and redox balance. Free Radical Biology & Medicine 2014; 71: 157-164.
Leilia Alberta Ritchie Scholarship, UGA College of Family and Consumer Sciences, 2020, Rebecca Gould
Graduate Scholarship, Northeast Georgia Dietetic Association, 2019, Rebecca Gould
Hazel and Gene Franklin Scholarship, UGA College of Family & Consumer Sciences, 2018, Rebecca Gould
Carolyn Berdanier Undergraduate Research Grant, UGA College of Family & Consumer Sciences, 2017, Emily Owen and Shriya Bhatnagar (Mentor: Rob Pazdro)
June and Bill Flatt Nutrition Excellence Graduate Fellowship, UGA College of Family & Consumer Sciences, 2017, Rebecca Gould
Ruth Rowan Morrison Graduate Endowment in Nutrition Studies and Anne and Earl Haltiwanger Scholarship, UGA College of Family & Consumer Sciences, 2017, Rebecca Gould
University of Georgia Amazing Student, 2016, Whitney Okie (Mentor: Rob Pazdro)
Faculty Mentoring Undergraduate Research Award, UGA College of Family & Consumer Sciences, 2015, Rob Pazdro
Meet the Lab