Alexa Mattheyses
University of Alabama at Birmingham, AL·Biophysics
Skin has to be pulled, stretched and rubbed without falling apart, and much of that toughness comes from desmosomes, button-like junctions that rivet neighboring cells together. A desmosome is built from cadherin proteins that span the cell membrane and grip their counterparts on the next cell, plus a dense internal plaque containing desmoplakin, which anchors the junction to the keratin intermediate filament cytoskeleton, the rope-like network that distributes mechanical stress.
- Fields
Biophysics
Biochemistry
Biology
- Topics
desmosomes
cell-cell adhesion
desmoplakin
- Grants
- 1 known grant, through Dec 2029
What they work on
- Define what drives changes in the architecture of desmoplakin, the plaque protein that links desmosomes to the keratin intermediate filament cytoskeleton, and test whether that architecture is what confers mechanical integrity, using super-resolution fluorescence microscopy.
- Determine the mechanism that imposes molecular order on desmosomal cadherins, the membrane-spanning proteins that grip neighboring cells, using protein chimeras that swap regions between proteins.
- Introduce genetic variants associated with inherited skin, hair and heart disorders into primary human keratinocytes to identify how altered protein architecture contributes to disease mechanisms.
- Test whether desmosome architecture responds to mechanical load by applying mechanical stimuli to keratinocytes and imaging protein organization in the junction.
More about the research
When desmosomes fail, the consequences are severe: inherited disorders cause skin and mucosal erosions and can also affect hair and the heart, and treatment options are limited. Because desmosomes are large and densely packed with proteins, there have been few ways to see how individual proteins are arranged inside them, which is the barrier this work addresses.
Why it matters
Faulty desmosomes underlie inherited skin and mucosal diseases that cause erosions and can also involve hair and heart tissue, and current treatments are limited. Linking specific disease-associated gene variants to specific defects in how desmosomal proteins are arranged could reveal why these mutations weaken adhesion and could guide therapies aimed at restoring desmosome structure in epithelial disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Sergey Troyanovsky
Northwestern University, IL·Biology
Determine how the basolateral polarity protein Scrib regulates the phosphatase PP1 and identify the effectors of this pathway in maintaining the identity of the epithelial cell's lower membrane.
Soichiro Yamada
University of California-Davis, CA·Biomedical Engineering
Identify the proteins that gather around keratin intermediate filaments in epithelial cells with and without applied force, by using promiscuous biotin labeling to chemically tag nearby proteins while cells are being mechanically stimulated.
Terry Lechler
Duke University, NC·Biology
Determine the molecular mechanisms that recruit mRNAs and translation regulators to desmosomes, the adhesion structures that bind skin cells together, at the cell edge.
The school
University of Alabama at Birmingham: 45 labs on PI Pages, $866M a year on research, 166 research doctorates a year.
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