Professor of Pharmacology and Toxicology;Medicine (Nephology) and Pediatrics (Medical Genetics)Director, Institutional Molecular and Genomics Core Facility (MGCF) Office: G309 (601) 984-4309 (office) (601) 984-2816 (lab)
The Garrett laboratory has a broad interest in understanding the genetic basis of complex diseases, including kidney disease, hypertension and preeclampsia. The laboratory take a multidisciplinary approach through the use of animal models, cell-culture, gene-editing, genetic and genomics methods, proteomics and bioinformatics. A major focus of the laboratory is on the identification of genes and pathways that play a role in the onset and progression of kidney disease associated with hypertension and pregnancy. It is hoped that a better understanding of kidney disease in the rat will ultimately provide novel diagnostic or therapeutic interventions for the treatment of human patients. We are actively working on four research projects:
Identification of Genetic Factors involved in Chronic Kidney Disease. Chronic kidney disease (CKD) or progressive decline in kidney function affects ~10% of adults in the US which can eventually lead to kidney failure. Hypertension is the second major cause of renal failure (only behind diabetes). The Dahl salt-sensitive (S) rat is a model of both aged related and salt-sensitive hypertension that develops significant kidney injury. Previous genetic studies have identified 10 genomic intervals linked to kidney injury in the S rat. We have linked genetic variants in two genes Arhgef11 (Chr.2) and Cgnl1 (Chr.8) with CKD in the Dahl S rat using genetically modified animals (SS-Arhgef11-/- and SS-Cgnl1-/-), gene-edited cell lines, and high throughput genomic methods, including bulk RNAseq, single nuclei RNAseq, and spatial transcriptomics.
Identification of Genetic Factors involved in Preeclampsia. Preeclampsia (PE) is a progressive hypertensive disorder of pregnancy affecting 2-8% of pregnancies. PE is a leading cause of maternal and fetal deaths, and many studies suggest that preeclampsia predisposes both the mother and offspring to developing cardiovascular diseases later in life. We have published extensively on the spontaneous preeclamptic phenotype that is exhibited by the Dahl salt-sensitive (Dahl S) during pregnancy. This model has provided important insight into both physiological and molecular changes associated with PE, potential therapeutic interventions, along with impact of microbiome complexity. We are actively working to apply genetic approaches via quantitative trait loci (QTL) mapping to identify genes/genetic variants causative to the development of PE in the Dahl S model. This project also involves using genetically modified animals, gene-edited cell lines, and high throughput genomic methods, including bulk RNAseq, single cell RNAseq, and spatial transcriptomics.
Genetics of Kidney Development and Association with CKD. Low nephron (functional unit of the kidney) numbers are associated with risk to develop hypertension and CKD, both of which have a significant impact on human health. We have developed a one-of-a-kind inbred genetic model, the HSRA rat. In the HSRA model, ~75% offspring are born (incomplete penetrance) with a single kidney (HSRA-S) compared to normal two-kidney littermates (HSRA-C, ~25%). HSRA-S rats develop age-related decline in renal function and hypertension compared to HSRA-C. With a detailed understanding of HSRA physiology, we are actively working to map quantitative trait loci (QTL) and identify genes/genetic variants linked to nephrogenesis through leveraging state-of-the-art methodologies, including single cell/spatial RNA sequencing, gene-edited zebrafish models, and conplastic strains (holding nuclear genome constant and only changing the mitochondrial genome).
SARS-CoV-2 in Mississippi and Association with Cardiovascular Disease. We are actively involved in performing whole viral sequencing of SARS-CoV-2 patient samples collected through the Medical Center and across Mississippi (MS). We are involved in two programs: (1) a SARS-CoV-2 Biosurveillance Program (in collaboration with Dr. Robinson in Microbiology), which provides weekly data on variants and lineages circulating in MS ; and (2) sequencing of archived SARS-CoV-2 samples collected from the beginning of the pandemic (May 1, 2020- ). The goal of this project is to model viral emergence, evolution, and spread of infection with a particular focus on racial disparities. The outcome of this research is to inform state and federal agencies(CDC) on SARS-CoV-2 variant/lineage to provide guidance to help adjust the timing and nature of public health interventions now and in future.