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  • Michael R. Garrett, PhD, MBA

     GarrettMichael_Pharmaweb.jpg

    Associate Professor
    Office: G327
    Phone: (601) 984-4309 (office)
                (601) 984-2816 (lab)
                (601) 984-1692
    E-mail: mrgarrett@umc.edu 

    View personal profile 

    Current research

    Our laboratory has a broad interest in understanding the genetic basis of complex diseases, including kidney disease, hypertension, and diabetes. We take a multidisciplinary approach to achieve this goal by utilizing animal models, cell-culture, genetic and genomics methods, proteomics, and bioinformatics. Our current focus is on the identification of novel 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 four research projects:

    • Project 1- Positional cloning 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 a genetic analysis [using the spontaneous hypertensive rat (SHR)] that identified 10 genomic intervals linked to kidney injury (proteinuria) in the S rat. We are actively working on two genomic intervals which include:
      • Chromosome 2: Using fine-mapping strategies, comprehensive sequencing and gene expression analysis, we have identified 4 genes that contain non-synonymous changes (amino acid changing) that may be directly linked with the development of kidney injury. We are currently conducting studies to better understand the functional significance of these genetic variants. Human studies have established that these genes are also linked to kidney disease in human populations.
      • Chromosome 11: We have developed a novel rat strain [S.SHR(11)] that more rapidly develops progressive renal injury and impaired renal function compared to the Dahl S. We are currently characterizing the model, as well as, conducting fine-mapping studies to identify the causative gene.
    • 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 unilateral renal agenesis. 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 are currently performing studies aimed at understanding the long-term risk of cardiovascular and kidney injury in the model.

    Selected publications

    • Packard, M., Saad, Y., Gupta, S., Gunning, W.T., Shapiro, J., Garrett, M.R., Investigating the Effect of Genetic Background on Renal Disease using Reciprocal Congenic Strains, American Journal of Physiology, Renal, 296(4):F839-46, 2009. PMID: 19176703. PubMed link 
    • Joe B., Saad Y., Lee N.H., Frank, B.C., Achinike, O.H., Luu, T.V., Gopalakrishnan, K., Toland, E.J., Farms, P., Yerga-Woolwine, S., Rapp, J.P., Garrett, M.R., Coe, D., Apte, S.S.,Rankinen, T., Pérusse, L., Ganesh, S., Cooper, R.S., Connor, A.A., Rice, T., Weder, A., Chakravarti, A. Rao, D.C. Bouchard, C., Positional Identification of Variants of ADAMTS16 Linked to Inherited Hypertension, Human Molecular Genetics, 18(15):2825-38, 2009. PMID: 19423552 PubMedCentral ID: PMC2706685. PubMed link 
    • Wiessner, J, Garrett, M.R., Roman, R.J., Mandel, N., Dissecting the Genetic Basis of Calcium Oxalate Stone Disease Using Chromosome Substitution Strains in the Rat, American Journal of Physiology, Renal, 297(2):F301-6, 2009. PubMedCentral ID: PMC2724241. PubMed link
    • Solberg Woods, L.C., Stelloh, C., Regner, K.R., Schwabe, T., Eisenhauer, J., and Garrett, M.R., Heterogeneous stock rats: a new model to study the genetics of renal phenotypes American Journal of Physiology, Renal, 298:(6) F1484-F1491, 2010
    • Garrett, M.R., Pezzolesi, M., and Korstanje, R., Integrating Human and Rodent Data to Identify the Genetic Factors Involved in Chronic Kidney Disease, Invited Review- Journal of the American Society of Nephrology Mar;21(3):398-405, 2010