Name: James Kramer
Title: Professor
Research area: Extracellular Matrix in Development
Degree: Ph.D., University of Michigan, Ann Arbor
Voice: 312.503.7644
Fax: 312.503.7912
e-mail: jkramer@northwestern .edu
Link to lab webpage: jimkramer.cmb.northwestern .edu/index.htm

Detailed research description:
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.

Representative publications:

Graham, P.L., Johnson, J.J., Wang, S., Sibley, M.H.,
  Gupta, M.C. and Kramer, J.M. (1997). Type IV collagen
  is detectable in most, but not all, basement membranes
  of C. elegans and assembles on tissues that do not
  express it. J. Cell Biol., 137:1171-1183.

Gupta, M.C., Graham, P.L. and Kramer, J.M. (1997).
  Characterization of a1(IV) collagen mutations in
  C. elegans and the effects of a1 and a2(IV) mutations
  on type IV collagen distribution. J. Cell Biol.,
  137:1185-1196.

Peixoto, C.A., de Melo, J.V., Kramer, J.M. and
  de Souza, W. (1998). Ultrastructural analyses of the
  Caenorhabditis elegans rol-6(su1006) mutant, which
  produces abnormal cuticle collagen. J. Parasitol.,
  84:45-49.

Bergmann, D.C., Crew, J.R., Kramer, J.M. and
  Wood, W.B. (1998). Cuticle chirality and body
  handedness in Caenorhabditis elegans. Dev.
  Genet., 23:164-174.

Yang, J. and Kramer, J.M. (1999). Proteolytic
  processing of Caenorhabditis elegans SQT-1 cuticle
  collagen is inhibited in right roller mutants whereas
  cross-linking is inhibited in left roller mutants . J.
  Biol. Chem., 274:32744-32749.

Su, M-W., Merz, D.C., Killeen, M.T., Zhou, Y.,
  Zheng, H., Kramer, J.M., Hedgecock, E.M.,
  and Culotti, J.G. (2000). Regulation of the UNC-5
  netrin receptor initiates the first reorientation of
  migrating distal tip cells in Caenorhabditis
  elegans. Development, 127:585-594.