James
Kramer,
PhD
Professor
Department of Cell and Molecular Biology
To Contact Dr. Kramer:
phone: 312-503-7644
e-mail: jkramer@northwestern.edu
Dr. Kramer's website
PubMed
Reference Lookup
Research Interests
The laboratory of Dr. James Kramer studies the structures and functions of
extracellular matrix molecules in the nematode Caenorhabditis elegans. Extracellular
matrices have critical functions in the development of all metazoans, as well
as in the pathogenesis of numerous diseases. C. elegans is the simplest metazoan
that can easily be genetically manipulated, making it a powerful system for
genetic studies of extracellular matrix functions.
There are two major forms
of extracellular matrix in C. elegans: the cuticle and basement membranes.
The cuticle serves as the exoskeleton and has important roles in determining
the animal's morphology and motility. Mutations in cuticle components can
cause dramatic morphological defects, such as helical twisting of the entire
animal.
Basement membranes are thin pericellular matrices that surround the internal tissues of all multicellular animals. Mutations in C. elegans basement membrane components can affect many developmental processes, including cell adhesion, cell and axon migrations, and cell differentiation.
Extracellular matrices
(ECMs) are critical for many aspects of development, including cell differentiation,
motility, morphogenesis, and integration of cells into tissues. Our research
focuses on understanding how ECMs are assembled and how they function in development.
ECM molecules have been highly conserved in all multicellular animals. We
study ECM in Caenorhabditis elegans because of the powerful genetic and molecular
approaches possible with this organism. There are two forms of ECM in C. elegans,
basement membranes and the cuticle.
Mutations in the genes
that encode the basement membrane-specific (type IV) collagen chains cause
embryonic lethality, demonstrating the importance of basement membranes in
development. Human Alport syndrome patients have similar mutations, so our
system serves as a model for this disease. We have identified mutations that
suppress the lethality of type IV collagen mutations, and these could lead
to possible therapies for patients with Alport syndrome. Surprisingly, we
find that type IV collagen can assemble at specific sites distant from the
cells where it is synthesized. We are examining other basement membrane components
that may direct type IV collagen assembly to the proper places. Our genetic
approaches may allow us to identify novel basement membrane components and
determine how they function in development.
We have identified mutations in collagens that are components of the cuticle (exoskeleton) of C. elegans. These mutations can cause dramatic alterations in the organism's morphology, such as helical twisting or blistering. Our characterization of these mutations has identified sites important for collagen processing and assembly into ordered macromolecular structures. We can analyze the effects of defined amino acid replacements by transforming in vitro mutagenized collagen genes back into C. elegans, thus elucidating how sequence changes in collagens alter their functions and ultimately the morphology of an entire organism.