PhD - 1990
Diabetes affects 29 million Americans and is the 6th leading cause of death in the US. Diabetic nephropathy is the most common cause of end-stage renal disease worldwide. This chronic and debilitating disease is characterized by progressive proteinuria, declining glomerular filtration rate, and increased risk for cardiovascular disease.Our research focuses on how the effects of two important hormonal systems, renin-angiotensin and endothelin, contribute to the failure of normal kidney blood vessel function and lead to the development and progression of kidney disease in type II diabetic patients. The research is focused on determining the role of intrarenal production of angiotensin and endothelin-1 via chymase-dependent pathways to the microvascular and glomerular dysfunction contributing to the progression of diabetic kidney disease. Most important, blocking the actions of a specific enzyme, chymase, may provide a new therapeutic drug target to reduce the influence of these hormonal systems on diabetic kidney disease. Our research utilizes the highly clinically relevant obese type II diabetic db/db mouse which exhibits many of the principal features of human diabetic nephropathy.
In vivo and in vitro experimental approaches will determine the deleterious effects of intrarenal chymase-dependent formation of angiotensin and endothelin-1 to diabetes induced nephropathy by measuring cardiovascular and kidney physiological function, molecular expression, enzymatic activity, peptide levels, and kidney histopathology during the progression of kidney disease in the diabetic mouse. Kidney microvascular responses to chymase-dependent generation of angiotensin and endothelin-1 are measured in blood perfused juxtamedullary nephrons of kidneys isolated from control and diabetic mice.
Teaching Expertise: Present: Renal Physiology to Medical, Graduate, Dental, Allied Health, and Undergraduate Nursing Students; Cardiovascular Physiology to Undergraduate Nursing Students
Course Directorship: 2008 - 2013: DHY 3202 - Dental Hygiene General and Oral Physiology
Co-Directorship: 2014 - 2016: HLSC 2410 - Nursing Human Physiology
Harrison-Bernard LM. Sphingolipids, new kids on the block, promoting glomerular fibrosis in the diabetic kidney. Editorial Focus for Am J Physiol Renal Physiol. 309: F685-F686, 2015. PMID: 26155845
Park S, Bivona BJ, Ford S, Xu S, Kobori H, de Garavilla L, Harrison-Bernard LM. Direct evidence for intrarenal chymase-dependent angiotensin II formation on the diabetic renal microvasculature. Hypertension 61(2):465-471, 2013. PMID:23213190
Herrera M, Sparks MA, Pecchio ARA, Harrison-Bernard LM, Coffman TM. Lack of specificity of commercial antibodies leads to misidentification of angiotensin type 1 receptor (AT1R) protein. Hypertension 61(1):253-258, 2013. PMID 23150519
Beierwaltes WH, Harrison-Bernard LM, Sullivan JC, Mattson DL. Assessment of renal function; clearance, the renal microcirculation, renal blood flow, and metabolic balance. Comprehensive Physiology. Renal Physiology. Editors: DM Pollock and J Garvin., http://onlinelibrary.wiley.com/doi/10.1002/cphy.c120008/full. January 1, 2013. DOI: 10.1002/ cphy.c120008
Kobori H, Kamiyama M, Harrison-Bernard LM, Navar LG. Cardinal role of the activated intrarenal renin-angiotensin system in the pathogenesis of diabetic nephropathy. J Investig Med. 61(2):256-264, 2013. PMID: 23266706
Kobori H, Harrison-Bernard LM, Navar LG. Role of activated renin-angiotensin system in the pathogenesis of diabetic nephropathy. “Advances in the pathogenesis of diabetic nephropathy" NovaScience Publishers, New York. Sharma S Prabhakar, MD (Editor) 161-197, 2012
Prieto MC, Das S, Somanna NK, Harrison-Bernard LM, Navar LG, Pandey KN. Disruption of Npr1 gene differentially regulates the juxtaglomerular and distal tubular renin levels in null mutant mice. Int J Physiol Pathophysiol Pharmacol 4(3):128-39, 2012. PMID: 23071870
Harrison-Bernard LM,Chappell MC. Unraveling the glomerular RAS - one peptidase at a time. Am J Physiol Renal Physiol; 303 (3): F373-F374, 2012. PMID: 22573374
Harrison-Bernard LM. Trapping intracellular ANG II to the proximal tubule: Powerful in vivo effects on sodium handling and blood pressure. Editorial Focus for Am J Physiol Renal Physiol, ajprenal.00115.2011; published ahead of print March 2, 2011, doi:10.1152/ajprenal.00115.2011.
Bivona BJ, Park S, Harrison-Bernard LM. Glomerular filtration rate determinations in conscious type II diabetic mice. Am J PhysiolRenal Physiol 300:F618-F625, 2011.PMID: 21147841
Park S, Bivona BJ, Kobori H, Seth DM, Chappell MC, Lazartigues E, Harrison-Bernard LM., Major role for ACE-independent intrarenal ANG II formation in type II diabetes., Am J Physiol Renal Physiol 298:F37-F48, 2010. This publication was selected as the 2010 American Journal of Physiology: Renal Physiology Paper of the Year
Related Editorial Focus. Lorenz JN., Chymase: The other ACE?, Am J Physiol Renal Physiol 298:F35-F36, 2010.
Harrison-Bernard LM., The renal renin-angiotensin system., Advan Physiol Edu 33: 270-274, 2009.