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Lihsia Chen, Ph.D.

Assistant Professor

Mailing Address:
University of Minnesota
Department of Genetics, Cell Biology, and Development
6-160 Jackson
321 Church St. SE
Minneapolis, MN 55455
USA
Education:
Ph.D., The Johns Hopkins University, 1995
Office:
4-110 MCB
P:612-625-1299

Email:
chenx260@umn.edu

 Lab:
4-218 MCB
P:612-625-3730

Areas of Research Strength:

Cell Adhesion and signaling
Membrane cytoskeleton and cell motility
Developmental mechanisms

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Research Techniques:

Classical and molecular genetics
Confocal and conventional light microscopy
Molecular and biochemical assays

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Research Interests:

Research description. Cell adhesion is essential to the organization
of multicellular organisms. Cell adhesion must be stable and strong
enough to maintain tissue integrity against forces exerted by the
environment and the organism itself. Yet it has to be dynamic enough
to allow cells to migrate during gastrulation and tissue morphogenesis.
This spectrum of cell adhesion events is typically mediated by the same
adhesion molecules. Thus to carry out such diverse, these cell adhesion
molecules have to integrate extracellular cues with various intracellular
signaling pathways. Impaired cell adhesion function has been shown
to lead to developmental malformations, tumor formation, and cancer
progression, adding to the importance of understanding how these
adhesion molecules work.

L1CAM functions. As a model, the Chen laboratory is focusing
on the function and regulation of the L1 family of cytoskeletally-linked c
ell adhesion receptors in C. elegans, using genetic, molecular and
biochemical approaches. Mutations in human L1 result in a neurological d
isorder whose symptoms are characterized by the acronym CRASH
(Corpus callosum hypoplasia, mental Retardation, Adducted thumbs,
Spastic paraplegia, and Hydrocephalus).

The lab determined that the C. elegans L1 homologue, LAD-1, is ubiquitously
expressed as early as when the two-cell embryo is developing and is localized
to the plasma membrane at sites of cellular contact. LAD-1 is also highly
expressed in the nervous system. We have several alleles of lad-1 and
are currently characterizing their mutant phenotypes. Initial characterization
indicates defects in the nervous system as well as in embryogenesis. Determination
of the molecular nature of these defects, which is currently underway, will help
better understand the aetiology of the CRASH syndrome.

L1CAM signal transduction. LAD-1 is linked to the spectrin-actin cytoskeleton
via the adaptor protein, ankyrin. The ankyrin binding motif, SFIGOY, which is located
in the LAD-1 cytoplasmic tail, is subjected to tyrosine-phosphorylation. This
phosphorylation event, which is dependent on the Fibroblast Growth Factor Receptor
(FGFR)-activated Ras pathway, abolishes ankyrin binding. The implication of this loss
of ankyrin binding is not known and is a major focus of our studies. Using antibodies
that recognize only phosphorylated LAD-1, we determined that phosphorylated
LAD-1 is localized to axon-muscle and epithelial adherens junctions. The function
and the localization mechanism of phosphorylated LAD-1 at these specialized
junctions are currently being determined.

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Selected Publications:

Xuelin Wang, Junghun Kweon, Stephanie Larson and Lihsia Chen. 2005. A role for the C. elegans L1CAM homologue lad-1/sax-7 in maintaining tissue attachment. Developmental Biology 284: 273-291.

Chen, L., Ong, B., and Bennett, V. 2001. LAD-1, the C. elegans L1CAM family homologue, has essential cell adhesion roles in the early embryo, participates in cell migration, and is a substrate for phosphotyrosine-based signaling. Journal of Cell Biology 154: 841-855

Bennett, V. and Chen, L. 2001. Ankyrins and cellular targeting of diverse membrane proteins to physiological sites. Current Opinion in Cell Biology 13:61-67.

Moorthy, S., Chen, L., and Bennett, V. 2000. C. elegans Beta-G spectrin is dispensable for establishment of epithelial polarity, but essential for muscular and neuronal function. Journal of Cell Biology 149: 915-930

Book Chapter:
Nass, R., Chen, L.  (In Press)  C. elegans models of human neurodegenerative diseases: a powerful tool to identify molecular mechanisms and novel therapeutic targets. Sourcebook of Model Organisms in Biomedical Research, ed. PM Conn. Humana Press. 

To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed
search menu should say PubMed
type Chen L in the avaliable line
please note: there are several people who use "Chen L"

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A. LAD-1 expression in early (i) and late (ii) embryos with robust expression in the developing nervous system.
B. Phosphorylated LAD-1 in the intestinal adherens junctions.
C. Phosphorylated LAD-1 localized in puncta at axon-muscle junctions.

 
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 Last modified on Thursday, July 26, 2007