Genetics and Genomics

Research in the field of genetics and genomics focuses on the analysis of complex and common disorders and their underlying genetic basis using animal and human studies. Investigators use animal models consomic and congenic rat strains, knock-out and transgenic rats and mice) or human studies combined with linkage analysis, single nucleotide polymorphism (SNP)-based association studies, and functional genomic analyses using transgenic rat and mouse models, microarray expression profiling, and siRNA to understand the mechanisms by which mutations affect organ function and integrity and ultimately lead to common disorders.

Genetic and Genomic Technologies and Applications

The department is widely recognized as a leader in the development of genetic and genomic technologies and the application of these technologies to study hypertension and other disorders.

Genetic & Physiological Basis of Salt-Sensitive Hypertension
Dr. Allen W. Cowley, Jr., leads an NIH Program Project Grant focusing on advancing our understanding of the complex regulation and interplay of a set of genes residing in two different regions of rat chr 13 but which together are responsible, in large measure, for salt-induced hypertension, renal injury, and vascularity/angiogenesis of the microcirculation in the salt-sensitive (SS) rat. The Program consists of three projects led by Dr. Cowley, Dr. Mingyu Liang, and Dr. Andrew Greene.

Gene Targeted Rat Resource
Innovative rat genome editing technologies, some of which developed by our faculty, are being applied to generate 250 gene targeted rat models nominated by the scientific community in a program led by Drs. Mindy Dwinell and Aron Geurts. The Resource provides phenotypic characterization, cryopreserved sperm from each line, along with a tissue and fibroblast primary culture bank for each strain, as well as distribution of all the animals and reagents to the community.

Advanced Genetic Engineering Technology Development
Studies led by Dr. Aron Geurts are using knockin technology to enable conditional mutagenesis and whole gene replacement approaches in the rat to develop new and valuable models to study hypertension.

Discovery and Functional Studies of Genes for Type 1 Diabetes GWAS Susceptibility Loci
Dr. Geurts is developing new animal models to investigate human T1D genes in a collaborative project.

microRNA and Epigenomics

The microRNA and epigenomic research in the department is concentrated in the Center of Systems Molecular Medicine (CoSMM) founded and directed by Dr. Mingyu Liang.

MicroRNA in Hypertension
Studies led by Dr. Liang are investigating the role of specific microRNAs such as miR-29 and miR-214 in the development of hypertension in animal models and human subjects.

MicroRNA in Cardioprotection
Dr. Liang is investigating the role of microRNA in the loss of cardioprotection in diabetic conditions using animal models and stem cells in a collaborative project.

Cardiorenal Syndrome and MicroRNA
Studies led by Dr. Alison Kriegel are examining the role of microRNAs in the development of cardiovascular disease in a model of chronic kidney disease.

Epigenomics of Hypertension
Dr. Liang directs one of the four centers in the nation that form the American Heart Association Strategically Focused Hypertension Research Network. The center consists of basic, clinical, and population science projects led by Dr. David Mattson, and Dr. Srividya Kidambi, working with Dr. Cowley, Dr. Pengyuan Liu, and other investigators. The three projects are collectively testing the hypothesis that lifestyle factors and gene-environment interactions cause genome-wide changes in DNA methylation, which contribute to the development of hypertension and can be used as predictive or diagnostic markers of hypertension and related diseases.

Genetic Analysis

Genetic Analysis of Respiratory Disorders
Studies in the department use different animal models to gain insight into the time-course of normal development of the ventilatory control system, as well as the effect of environmental and genetic influences on these changes during development. A newborn piglet model is being used to determine whether a critical window of development exists in the ventilatory control system that has been proposed as a part of a triple-risk model in Sudden Infant Death Syndrome. In addition, the interaction of plasticity and genetic influences is being studied using inbred strains of rats exposed to perinatal hyperoxia.

Other projects use consomic rat models generated as part of the Program for Genomic Applications (PGA) to elucidate genes that contribute to the control of breathing. In combination, these studies are aimed at understanding how the ventilatory control system matures under both normal and stressed conditions. All these studies relate primarily to disease conditions of central and obstructive sleep apnea, Sudden Infant Death syndrome, congenital central alveolar hypoventilation, and traumatic brainstem injury.