Main Content

Michael R. Garrett, PhD, MBA

Professor of Pharmacology and Toxicology
Associate Professorof Medicine (Nephology)
Director, Institutional Molecular and Genomics Core Facility (MGCF)
Office: G327
(601) 984-4309 (office)
(601) 984-2816 (lab)
(601) 984-1692

Research interests

  • Genetics of complex diseases
  • Renal physiology
  • Cardiovascular physiology
  • Genomic technologies

Current research

My laboratory has a broad interest in understanding the genetic basis of complex diseases, including kidney disease, hypertension and diabetes. The laboratory take a multidisciplinary approach through the use of animal models, cell-culture, genetic and genomics methods, proteomics and bioinformatics. The current focus of the laboratory is on the identification of genes and pathways that play a role in the onset and progression of kidney disease. 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 three research projects:

  • Project 1:Identification of Genetic Factors involved in Chronic Kidney Disease (CKD) using Dahl Salt-Sensitive (S) rat. Chronic kidney disease (CKD) or progressive decline in kidney function affects ~10% of adults in the United States 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 salt-sensitive hypertension that develops significant kidney injury. We previously performed genetic analyses [using the spontaneous hypertensive rat (SHR)] that identified 10 genomic intervals linked to kidney injury (proteinuria) in the S rat. We have successfully identified the gene that underlies the genomic locus on chromosome 2 (Arhgef11) and subsequently have worked out a detailed mechanism/pathway of how genetic variants in this gene can lead to kidney injury. We are actively working on other genomic intervals to identify additional genetic factors involved in kidney disease.
  • Project 2:Understanding the Role of Nr4a1 in Kidney Disease. The NR4A subgroup of nuclear hormone receptors (NR) have been implicated in apoptosis, cancer, atherosclerosis, and most prominently in metabolic disease. However, the role of NR4A in the kidney is not well-understood. We are currently investigating the role of Nr4a1 (nuclear receptor subfamily 4, group A, member 1) in the development of kidney injury using knockout rats (Nr4a1-/-). The gene knockout is on the Fawn hooded hypertensive (FHH) rat - another model of hypertensive related kidney disease. We have performed detailed physiological characterization of these animals as well as microarray experiments to understand the molecular mechanisms linked to loss of Nr4a1 in the kidney.
  • Project 3:Physiological and Genetic Basis of Congenital Abnormalities of Kidney and Urinary Tract (CAKUT). Unilateral renal agenesis (URA) or being born with a single kidney is a relatively common developmental defect in both males and females that occurs in 1:500 to 1:1000 births. Some studies suggest that patients born with one-kidney are at increased risk for kidney injury, hypertension, and kidney failure. However, the lack of a good animal model has made investigating the long-term consequences of URA difficult. Recently, we developed a new animal model of spontaneous URA (i.e., the heterogeneous stock derived model of unilateral renal agenesis, (HSRA)]. We have completed several detailed studies that assessed the long-term risk of cardiovascular and kidney injury in the model and recently began work to elucidate the genetic cause by genetic analysis involving whole genome sequencing and positional cloning.

Selected publications

  • Westbrook L, Johnson AC, Regner KR, Williams JM, Mattson DL, Kyle PB, Henegar JR, Garrett MR. Genetic susceptibility and loss of Nr4a1 enhances macrophage-mediated renal injury in CKD. J Am Soc Nephrol. 2014 Nov;25(11):2499-510. PMID: 24722447; PubMed Central PMCID: PMC4214519.
  • Wang X, Johnson AC, Williams JM, White T, Chade AR, Zhang J, Liu R, Roman RJ, Lee JW, Kyle PB, Solberg-Woods L, Garrett MR. Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model. J Am Soc Nephrol. 2014 Oct 27;PubMed PMID: 25349207.
  • Jia Z, Johnson AC, Wang X, Guo Z, Dreisbach AW, Lewin JR, Kyle PB, and Garrett MR. Allelic Variants in Arhgef11 via the Rho-Rock Pathway are linked to Epithelial-Mesenchymal Transition and Contributes to Kidney Injury in the Dahl S Rat. PLOS One (in revision), 2015.