Current genetic studies are largely biased towards European populations, leaving the discovery of genomics biomarkers and causative genetic variants unexplored in minority populations, such as African Americans. Meanwhile, African Americans are disproportionately affected by a variety of complex diseases and respond differently to many drug treatments. The disparity is due...
The protein homeostasis (proteostasis) network, a critical cytoprotective system that restores homeostasis in response to molecular stress, comprises distinct pathways, including the heat-shock response, unfolded protein response, oxidative stress response, and autophagy. These distinct pathways are all co-opted by tumor cells to cope with cancer-associated stress, and their activation in...
Evolutionary theory predicts that reproduction entails energetic costs that detract from somatic maintenance, accelerating biological aging. In women, such ‘costs of reproduction’ (CoR) are thought to arise predominantly during pregnancy and lactation, while in men the physiological effects of the steroid hormone testosterone (T) are believed to be a major...
Heart failure due to genetic cardiomyopathy is associated with a range of phenotypic expression. The studies in this body of work interrogated the role of noncoding variation in modifying cardiomyopathy phenotypes. We used cap analysis of gene expression in heathy and failed left ventricles to define the regulatory environment of...
Over 6 million adults in the United States have heart failure, a serious public health problem. Differences in the progression of heart failure are in part due to variability in sex, age, and genetic variation background including ancestry. Medical biobanks provide a resource to study this variability as they include...
Understanding the complex genome-phenome associations behind human complex traits will be a primary focus for the practice of precision medicine in the future. Identifying the genetic variants that contribute to the inter- and intra- phenotypic variations of individuals, elucidating pleiotropic architecture of common complex traits, and demonstrating how personal biomedical...
Phenotypic variation is the functional unit that evolution acts upon and is the main contributor to the diversity of species. The phenotype of an individual is shaped by genetic and environmental factors. These genetic and environmental factors contribute to biomedically relevant traits such as an individual’s susceptibility to disease and...
The epidemic of obesity and associated metabolic diseases have led to increased scrutiny of adipose tissue and its primary cell type, the adipocyte. However, studies show that regional adipose tissue distribution rather than obesity per se is a major determinant of metabolic disease risk. Despite having an obese body mass...
The blueprint of life is contained within the sequence of an organism’s genome. While virtually all cells of an individual multicellular eukaryotic organism contain a near identical code of nucleic acid sequences, an organism must give rise to and maintain a varied set of cells and phenotypes. As such, sequence...
Neisseria gonorrhoeae (Ng), a strict human pathogen, is the sole causative agent of gonorrhea. Gc possess a complex gene conversion system, the pilin antigenic variation system, (pilin Av), which alters the DNA sequence of the major pilin, PilE. Pilin Av results in the constant alteration of the surface exposed appendage,...