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  • Jan M. Williams, PhD

     JWilliams.jpgAssistant Professor
    Office: Research Wing, R400
    Phone: (601) 984-1634
    Lab: (601) 984-1626
    E-mail: JMWilliams5@umc.edu

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    Research interests

    • Renal physiology
    • Diabetes and hypertension-induced nephropathy

    Current research

    Hypertension- and diabetes are the most common causes of chronic kidney failure and end-stage renal disease (ESRD). The direct cost for Medicare treatment of the 400,000+ patients with ESRD exceeds $35 billion per year not including the cost to treat another 20 million people who exhibit progressive decline in kidney function. The prevalence of ESRD in African Americans with hypertension or diabetes is 4 times higher than in Caucasians. Despite the magnitude of these problems, little is known about the initiating factors underlying the pathogenesis of diabetes-induced nephropathy due to the lack of appropriate animal models that mimic the progression of the human disease.

    Over the last few years, my laboratory has characterized several diabetic rodent models of chronic kidney disease such as the streptozotocin (STZ, Type 1)-Dahl salt-sensitive (S) and Type 2 Diabetic Nephropathy (T2DN) rats. Dahl S and T2DN rats are genetic models of hypertensive renal disease that develop progressive proteinuria, focal segmental glomerulosclerosis (FSGS) and renal fibrosis which eventually progress to ESRD. Both model systems exhibit histological changes in the kidney that resemble the lesions seen in patients with hypertension and diabetes such as thickening of the glomerular and tubular basement membranes, glomerular hypertrophy and mesangial matrix expansion. Previous studies have demonstrated that the early stages of diabetes are associated with increases in glomerular capillary pressure (Pgc) and glomerular filtration rate (GFR) that initiates the development of proteinuria and renal injury. However, the mechanism by which early alteration changes in renal hemodynamics promote the development of diabetes-induced nephropathy remains unclear.

    Our laboratory has found that the expression of matrix metalloproteases (MMPs) are increased during the progression of renal injury in STZ-treated Dahl S and T2DN rats, and treatment with inhibitors of MMPs prevents the development of proteinuria and renal disease. The main focus of my laboratory is to determine the role of MMPs during the progression of diabetes-induced renal injury. Regardless of the mechanism involved, our data indicate that MMP inhibitors hold the potential to prevent the progression of renal disease in the millions of patients suffering from chronic kidney disease.

    Selected publications

    • Williams JM, Johnson AC, Stelloh C, Dreisbach AC, Franceschini N, Regner KR, Townsend RR, Roman RJ, and Garrett MR. (2012) Genetic Variants in ARHGEF11 are associated with kidney injury in the Dahl salt-senstitve rat, Hypertension. (accepted for publication)
    • Sawyer RT, Flynn ER, Hutchens ZM Jr, Williams JM, Garrett MR, and Maric-Bilkan C. (2012) Renoprotective effects of C-peptide in the Dahl salt-sensitive rat, Am J Physiol Renal Physiol, Jul 18. PubMed article 
    • Regner KR, Harmon AC, Williams JM, Stelloh C, Johnson AC, Kyle PB, Lerch-Gaggl A, White SM, Garrett MR. (2012) Increased susceptibility to kidney injury by transfer of genomic segment from SHR onto Dahl S genetic background, Physiol Genomics 44, 629-37. PubMed article 
    • Fernandez, M. M., Gonzalez, D., Williams, J. M., Roman, R. J., and Nowicki, S. (2012) Inhibitors of 20-hydroxyeicosatetraenoic acid (20-HETE) formation attenuate the natriuretic effect of dopamine, European journal of pharmacology 686, 97-103. PubMed article 
    • Murphy, S. R., Dahly-Vernon, A. J., Dunn, K. M., Chen, C. C., Ledbetter, S. R., Williams, J. M., and Roman, R. J. (2012) Renoprotective effects of anti-TGF-beta antibody and antihypertensive therapies in Dahl S rats, American journal of physiology. Regulatory, integrative and comparative physiology 303, R57-69. PubMed article 
    • Williams, J. M., Fan, F., Murphy, S., Schreck, C., Lazar, J., Jacob, H. J., and Roman, R. J. (2012) Role of 20-HETE in the antihypertensive effect of transfer of chromosome 5 from Brown Norway to Dahl salt-sensitive rats, American journal of physiology. Regulatory, integrative and comparative physiology 302, R1209-1218. PubMed article 
    • Moreno, C., Williams, J. M., Lu, L., Liang, M., Lazar, J., Jacob, H. J., Cowley, A. W., Jr., and Roman, R. J. (2011) Narrowing a region on rat chromosome 13 that protects against hypertension in Dahl SS-13BN congenic strains, American journal of physiology. Heart and circulatory physiology 300, H1530-1535. PubMed article 
    • Williams, J. M., Zhang, J., North, P., Lacy, S., Yakes, M., Dahly-Vernon, A., and Roman, R. J. (2011) Evaluation of metalloprotease inhibitors on hypertension and diabetic nephropathy, American journal of physiology. Renal physiology 300, F983-998. PubMed article 
    • Williams, J. M., Burke, M., Lazar, J., Jacob, H. J., and Roman, R. J. (2011) Temporal characterization of the development of renal injury in FHH rats and FHH.1BN congenic strains, American journal of physiology. Renal physiology 300, F330-338. PubMed article
    • Williams, J. M., Murphy, S., Burke, M., and Roman, R. J. (2010) 20-hydroxyeicosatetraeonic acid: a new target for the treatment of hypertension, Journal of cardiovascular pharmacology 56, 336-344. PubMed article 
    • Williams, J. M., Sarkis, A., Hoagland, K. M., Fredrich, K., Ryan, R. P., Moreno, C., Lopez, B., Lazar, J., Fenoy, F. J., Sharma, M., Garrett, M. R., Jacob, H. J., and Roman, R. J. (2008) Transfer of the CYP4A region of chromosome 5 from Lewis to Dahl S rats attenuates renal injury, American journal of physiology. Renal physiology 295, F1764-1777. PubMed article
    • Williams, J. M., Sharma, M., Anjaiahh, S., Falck, J. R., and Roman, R. J. (2007) Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the glomerular protein permeability barrier, American journal of physiology. Renal physiology 293, F501-505. PubMed article  
    • Williams, J. M., Sarkis, A., Lopez, B., Ryan, R. P., Flasch, A. K., and Roman, R. J. (2007) Elevations in renal interstitial hydrostatic pressure and 20-hydroxyeicosatetraenoic acid contribute to pressure natriuresis, Hypertension 49, 687-694. PubMed article