Jeffrey H. Miner, PhD, FASN
Professor of Medicine, Division of Nephrology
- Phone: 314-362-8235
- Email: firstname.lastname@example.org
- Professor, Cell Biology and Physiology
Glomerular basement membrane (GBM), extracellular matrix, Alport syndrome, Pierson syndrome, CAKUT, laminin, collagen, nephrotic syndrome, proteinuria
Funding: NIH/NIDDK, Alport Syndrome Foundation/Pedersen Foundation/Kidney Foundation of Canada, Roche
A major interest of my laboratory is the role of basement membrane components in kidney function and disease, with particular emphasis on the glomerular basement membrane (GBM) as a component of the glomerular filtration barrier to albumin. Several genetic and acquired diseases of the kidney affect the GBM, causing thinning or thickening. We are focusing on the laminin and type IV collagen components of the GBM that are mutated in Pierson syndrome (a congenital nephrotic syndrome) and Alport syndrome (hereditary glomerulonephritis), respectively. We have produced knockout mice lacking relevant laminin or collagen IV chains to determine their functions in the kidney and elsewhere. We have also generated transgenic mice expressing mutant versions of laminin beta2 to understand why the mutations cause human kidney disease, using both standard transgenesis and CRISPR/Cas9-mediated appraoches. We have performed proof-of-principle studies to show that the abnormal GBM that is present in Alport syndrome can be normalized by restoring expression of the missing collagen IV network.
Another aspect of my research concerns the role of cell-cell junction/polarity proteins in urogenital development. We have generated mice lacking proteins associated with the Scribble complex (including Scribble, discs large 1, and CASK) and find interesting developmental anomalies, including renal hypoplasia or agenesis; defects in maturation of the distal ureter and its connection to the bladder; and glomerular cyst formation. These defects are observed in human congenital anomalies of the kidney and urinary tract (CAKUT) and in cystic diseases. We are using state of the art methods to investigate the mechanisms for these defects and to determine whether mutations in these genes are involved in human CAKUT.
Funk, SD, Bayer, RH, Malone, AF, McKee, KK, Yurchenco, PD, and Miner, JH. Pathogenicity of a human laminin ß2 mutation revealed in models of Alport syndrome. J. Amer. Soc. Nephrol. In press (2018).
Kim, AH, Chung, JJ, Akilesh, S, Koziell, A, Jain, S, Hodgin, JB, Miller, MJ, Stappenbeck, TS, Miner, JH, and Shaw, AS. B cell-derived IL-4 acts on podocytes to induce proteinuria and podocyte foot process effacement. JCI Insight 2(21): 81836 (2017).
Brähler, S, Zinselmeyer, BH, Raju, S, Nitschke, M, Suleiman, H, Saunders, BT, Johnson, MW, Boehner, A, Viehmann, S, Theisen, DJ, Kretzer, NM, Briseno, CG, Zaitsev, K, Ornatsky, O, Chang, Q, Carrero, JA, Kopp, JB, Artyomov, MN, Kurts, C, Murphy, KM, Miner, JH, and Shaw, AS. Opposing roles of dendritic cell subsets in experimental glomerulonephritis. J. Amer. Soc. Nephrol. In press (2017).
Suleiman, HY, Roth, R, Jain, S, Heuser, JE, Shaw, AS*, and Miner, JH*. Injury-induced actin cytoskeleton reorganization in podocytes revealed by super-resolution microscopy. JCI Insight 2(16): 94137 (2017). *Co-corresponding authors
Lawrence, MG, Altenburg, MK, Sanford, R, Willet, JD, Bleasdale, B, Ballou, B, Wilder, J, Li, F, Miner, JH, Berg, UB, and Smithies, O. Permeation of macromolecules into the renal glomerular basement membrane and capture by the tubules. Proc. Natl. Acad. Sci. USA 114: 2958-2963 (2017).
Malone, AF, Funk, SD, Alhamad, T, and Miner, JH. Functional assessment of a novel COL4A5 splice region variant and immunostaining of plucked hair follicles as an alternative method of diagnosis in X-linked Alport syndrome. Pediatr. Nephrol. 32: 997-1003 (2017).
Randles, MJ, Collinson, S, Starborg, T, Mironov, A, Krendel, M, Koenigshausen, E, Sellin, L, Roberts, ISD, Kadler, KE, Miner, JH, and Lennon, R. Three-dimensional electron microscopy reveals the evolution of glomerular barrier injury. Sci. Rep. 6: 35068 (2016).
Jarad, G, Knutsen, RH, Mecham, RP, and Miner, JH. Albumin contributes to kidney disease progression in Alport syndrome. Am. J. Physiol. Renal Physiol. 311: F120-130 (2016).
Lin, C, Werner, R, Ma, L, and Miner, JH. Requirement for basement membrane laminin α5 during urethral and external genital development. Mech. Dev. 141: 62-69 (2016).
Chung, J-J, Huber, TB, Gödel, M, Jarad, G, Hartleben, B, Kwoh, C, Keil, A, Karpitskiy, A, Hu, J, Huh, CJ, Cella, M, Gross, RW, Miner, JH, and Shaw, AS. Albumin-associated free fatty acids induce macropinocytosis in podocytes. J. Clin. Invest. 125: 2307-2316 (2015).
Korstanje, R, Caputo, CR, Doty, RA, Cook, SA, Bronson, RT, Davisson, MT, and Miner, JH. A mouse Col4a4 mutation causing Alport glomerulosclerosis with abnormal collagen α3α4α5(IV) trimers. Kidney Int. 85: 1461-1468 (2014).
Lin, X, Suh, JH, Go, G, and Miner, JH. Feasibility of repairing glomerular basement membrane defects in Alport syndrome. J. Amer. Soc. Nephrol. 25: 687-692 (2014).
Suleiman, H, Zhang, L, Roth, R, Heuser, JE, *Miner, JH, *Shaw, AS, and Dani, A. Nanoscale protein architecture of the kidney glomerular basement membrane. Elife 2013;2:e01149 (2013). *Co-corresponding authors
Chen, YM, Zhou, Y, Go, G, Marmerstein, JT, Kikkawa, Y, and Miner, JH. Laminin ß2 gene missense mutation produces endoplasmic reticulum stress in podocytes. J. Amer. Soc. Nephrol. 24: 1223-1233 (2013).