Jane
Wu, MD, PhD
Charles Louis Mix Professor of Neurology
Department of Neurology and Center for Genetic Medicine
To Contact Dr. Wu:
303 E. Superior St.
Lurie 6-117
Chicago, IL 60611
phone: 312-503-0684
fax: 312-503-5607
email:jane-wu@northwestern.edu
Dr. Wu’s website
Research Interests:
The laboratory of Dr. Jane Wu seeks to elucidate the pathogenetic mechanisms underlying neurodegenerative disorders. The lab is interested in understanding how genetic mutations affect the expression and function of genes important for cell death and critical for the pathogenesis of neurodegenerative diseases. The lab is also focusing on two areas of research: the role of pre-mRNA splicing regulation in neurodegeneration and the molecular mechanisms modulating cell migration.
Pre-mRNA splicing is a crucial step for gene expression because the vast
majority of human genes contain one or more intervening sequences (introns)
that must be accurately removed to form the mature and functional messenger
RNAs (mRNAs). Alternative splicing is a major mechanism for regulating mammalian
gene expression and for generating the complexity of human proteomes. Mutations
that affect pre-mRNA splicing cause a large number of diseases. Alternative
splicing regulates the expression and function of programmed cell death (PCD)
genes. A number of PCD genes, including Bcl-x, ced4/APAF1 and caspases, produce
functionally antagonistic products by undergoing alternative splicing. We
have established a model using the caspase-2 (casp-2) gene. An intronic regulatory
element has been identified to control the balance between anti-apoptotic
and pro-apoptotic isoforms of casp-2 gene products. Similar intronic elements
are present in other human caspase genes in the regions critical for their
enzymatic activities. These intronic elements may play a role in regulating
the formation of functionally antagonistic caspase gene products. Our work
has provided direct evidence that splicing factors can regulate casp-2 alternative
splicing and has suggested that alternative splicing may be an important regulatory
mechanism for PCD. We are using molecular, biological and biochemical approaches
to dissecting cis-elements and trans-factors critical for alternative splicing
regulation of caspase genes. We are testing whether cell death signals such
as chemotherapeutic reagents trigger changes in the expression or function
of splicing regulators. This work will not only further our understanding
of PCD regulation but also provide insights for designing new therapies for
diseases associated with excessive or insufficient cell death, including inflammation
and cancer.