Jeffrey H. Miner, Ph.D.

Internal Medicine
Cell Biology and Physiology

Molecular Cell Biology Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-362-8235

  • 314-362-8234

  • 314-362-8237

  • 8126

  • 7717 Wohl Clinic



  • cell adhesion, extracellular matrix, integrin biology, skin, kidney

  • Genetic analyses of mouse organogenesis and disease in kidney and skin

Research Abstract:

My research has three major focuses. The first deals with the roles of basement membranes, a specialized extracellular matrix, in embryonic development, organ function, and disease. Of particular interest are members of the laminin and collagen IV families and their roles in the kidney. We have generated laminin and Col4 knockout mice that model distinct human genetic kidney diseases (Pierson and Alport syndromes, respectively) and used them to show that laminin and collagen IV are critical for maturation and function of the glomerular basement membrane, a component of the kidney’s filtration apparatus. One interest of the lab is to define exactly what structure—cell or matrix—serves as the kidney’s filtration barrier. We are using mouse models of human kidney diseases (Alport syndrome and Pierson syndrome) to test potential therapies with both NIH and industry funding.

My second major interest is to define the mechanism whereby mouse discs large 1 (DLG1), a PDZ scaffolding protein, mediates normal development and function of the ureter. In the absence of DLG1, ureteric smooth muscle cells are misaligned, leading to impaired transport of urine from the kidney to the bladder. This hydroureter/hydronephrosis defect is a common problem in children. We are also studying mutant mice lacking CASK and Scribble, proteins that physically interact with DLG1. We have found that DLG1 and CASK cooperate to maintain the nephron progenitor cell population during kidney development and that Scribble is important for proper lower urinary tract development. These studies reveal novel roles for these cell polarity/scaffolding proteins.

My third major interest concerns the role of fatty acid transport protein 4 (FATP4) in skin and hair development. We discovered that mutation of FATP4 results in “wrinkle free” mice. These mice have very tight, thick skin and die shortly after birth because they are unable to breathe properly. In addition, grafted skin from the mutant exhibits impaired hair growth. We are now using biochemical, cell biological, and mass spectrometric techniques to determine the mechanism whereby FATP4 activity leads to normal skin development, normal hair growth, and normal sebaceous gland structure and function. Mutations in human FATP4 were discovered in patients displaying ichthyosis prematurity syndrome, so our studies of the Fatp4 mutant mice have implications for this human disease.

Selected Publications:

Lin, M-H and Miner, JH. Fatty acid transport protein 1 can compensate for fatty acid transport protein 4 in the developing mouse epidermis. J. Invest. Dermatol. 135: 462-470 (2015). PMCID: PMC4289464

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). PMCID: PMC3968506

Kim, ST, Ahn, S-Y, Swat, W, and Miner, JH. DLG1 influences distal ureter maturation via a non-epithelial cell autonomous mechanism involving reduced retinoic acid signaling, Ret expression, and apoptosis. Dev. Biol. 390: 160-169 (2014). PMCID: PMC4038003

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). PMCID: PMC4040157

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). PMCID: in process *Co-Corresponding Authors.

Chen, YM, Zhou, Y, Go, G, Marmerstein, JT, Kikkawa, Y, and Miner, JH. Laminin β2 gene missense mutation produces endoplasmic reticulum stress in podocytes. J. Amer. Soc. Nephrol. 24: 1223-1233 (2013). PMCID: PMC3736718

Ahn, S-Y, Kim, Y, Kim, ST, Swat, W, and Miner, JH. Scaffolding proteins DLG1 and CASK cooperate to promote nephron progenitor proliferation and migration. J. Amer. Soc. Nephrol. 24: 1127-1138 (2013). PMCID: PMC3699830

Lin, M-H, Hsu, F-F, and Miner, JH. Requirement of fatty acid transport protein 4 for development, maturation, and function of sebaceous glands in a mouse model of ichthyosis prematurity syndrome. J. Biol. Chem. 288: 3964-3976 (2013). PMCID: PMC3567649

Suh, JH, Jarad, G, VanDeVoorde, R, and Miner, JH. Forced expression of laminin beta1 in podocytes prevents nephrotic syndrome in mice lacking laminin beta2, a model for Pierson syndrome. Proc. Natl. Acad. Sci USA 2011 108: 15348-15353. PMCID: PMC3174642

Chen, YM, Kikkawa, Y, and Miner, JH. A missense LAMB2 mutation causes congenital nephrotic syndrome by impairing laminin secretion. J. Amer. Soc. Nephrol. 2011 22: 849-858. PMCID: PMC3083307

Last Updated: 4/1/2015 9:24:26 AM

In the developing kidney, nephron stem cells (green) are induced by the branching ureteric bud (red) to differentiate into filtration units (purple).
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