- Skin and Cellular Biology Research
- Hair Growth and Disorders
- Cellular Mechanics and Interactions
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Dermatological and Skeletal Disorders
- Chemokine receptors and signaling
- Thyroid Disorders and Treatments
- Wnt/β-catenin signaling in development and cancer
- Cancer Research and Treatments
- Silk-based biomaterials and applications
- Plant Reproductive Biology
- Wound Healing and Treatments
- RNA regulation and disease
- melanin and skin pigmentation
- Nanoparticle-Based Drug Delivery
- Growth Hormone and Insulin-like Growth Factors
- Nuclear Structure and Function
- Dermatologic Treatments and Research
- Fungal and yeast genetics research
- Skin Protection and Aging
- Nail Diseases and Treatments
- Dyeing and Modifying Textile Fibers
- Microtubule and mitosis dynamics
- Neonatal Respiratory Health Research
University of Michigan
2003-2025
Michigan United
2019-2024
U-M Rogel Cancer Center
2022
Johns Hopkins University
2012-2021
Michigan Medicine
2019-2021
Sidney Kimmel Comprehensive Cancer Center
2016-2019
Johns Hopkins Medicine
2007-2017
Kennedy Krieger Institute
2005
Centre National de la Recherche Scientifique
2002
Institut Pasteur
2002
Keratins are intermediate filament–forming proteins that provide mechanical support and fulfill a variety of additional functions in epithelial cells. In 1982, nomenclature was devised to name the keratin were known at point. The systematic sequencing human genome recent years uncovered existence several novel genes their encoded proteins. Their naming could not be adequately handled context original system. We propose new consensus for relies upon extends 1982 system adheres guidelines...
Injury to stratified epithelia causes a strong induction of keratins 6 (K6) and 16 (K16) in post-mitotic keratinocytes located at the wound edge. We show that K6 K16 occurs within h after injury human epidermis. Their subsequent accumulation correlates with profound reorganization keratin filaments from pan-cytoplasmic distribution one which are aggregated juxtanuclear location, opposite direction cell migration. This filament coincides additional cytoarchitectural changes onset...
Idiopathic Pulmonary Fibrosis (IPF) is a progressive scarring disease arising from impaired regeneration of the alveolar epithelium after injury. During regeneration, type 2 epithelial cells (AEC2s) assume transitional state that upregulates multiple keratins, and ultimately differentiate into AEC1s. In IPF, AECs accumulate with ineffectual AEC1 differentiation. However, whether how cause fibrosis, keratins regulate cell accumulation why fibrosis resolve in mouse models but IPF are unclear....
A group of keratin intermediate filament genes, the type II
The type I keratin 17 (K17) shows a peculiar localization in human epithelial appendages including hair follicles, which undergo growth cycle throughout adult life. Additionally K17 is induced, along with K6 and K16, early after acute injury to skin. To gain further insights into its potential function(s), we cloned the mouse gene investigated expression during skin development. Synthesis of protein first occurs subset cells within single-layered, undifferentiated ectoderm embryonic day 10.5...
Mice lacking desmin produce muscle fibers with Z disks and normal sarcomeric organization. However, the muscles are mechanically fragile degenerate upon repeated contractions. We report here a human patient severe generalized myopathy aberrant intrasarcoplasmic accumulation of intermediate filaments. Muscle tissue from this lacks wild-type allele has gene mutation encoding 7-aa deletion within coiled-coil segment protein. show that recombinant harboring cannot form proper filament networks...
Because of extraordinarily tight coiled-coil associations type I and II keratins, the composition structure keratin subunits has been difficult to determine. We report here use novel genetic biochemical methods explore early stages filament assembly. Using bacterially expressed humans K5 K14, we show that remarkably, these keratins behave as 1:1 complexes even in 9 M urea presence a reducing agent. Gel filtration chromatography chemical cross-linking were used identify heterodimers...
The ability to sense changes in the environment is essential for survival because it permits responses such as withdrawal from noxious stimuli and regulation of body temperature. Keratinocytes, which occupy much skin epidermis, are situated at interface between external body's internal milieu, have long been appreciated their barrier function against insults. recent discovery temperature-sensitive transient receptor potential vanilloid (TRPV) ion channels keratinocytes has raised possibility...
Previously we demonstrated that transgenic mice expressing a mutant keratin in the basal layer of their stratified squamous epithelia exhibited phenotype bearing resemblance to subclass (Dowling Meara) heterogeneous group human skin disorders known as epidermolysis bullosa simplex (EBS) (Vassar, R., P. A. Coulombe, L. Degenstein, K. Albers, E. Fuchs. 1991. Cell. 64:365-380.). The extent which subtypes EBS diseases might be genetically related is unknown, although they all exhibit blistering...
The ability to heal wounds is vital all organisms. In mammalian tissues, alterations in intermediate filament (IF) gene expression represent an early reaction of cells surviving injury. We investigated the role keratin IFs during epithelialization skin using a 6α and 6β (K6α/K6β)-null mouse model. explant culture, null keratinocytes exhibit enhanced potential due increased migration. extent phenotype strain dependent, accompanied by IF F-actin organization. However, wounded vivo, rupture as...
Keratins K14 and K5 have long been considered to be biochemical markers of the stratified squamous epithelia, including epidermis (Moll, R., W. Franke, D. Schiller, B. Geiger, R. Krepler. 1982. Cell. 31:11-24; Nelson, W., T.-T. Sun. 1983. J. Cell Biol. 97:244-251). When cells most epithelia differentiate, they downregulate expression mRNAs encoding these two keratins induce new sets specific for individual programs epithelial differentiation. Frequently, as in case epidermis,...