Ann
Harris, PhD
Professor, Pediatrics
Director, Human Molecular Genetics Program, CMRC
To Contact Dr. Harris:
2300 Children's Plaza
Box 211
Chicago, IL 60614
phone: 773-755-6525
e-mail: ann-harris@northwestern.edu
Dr. Harris' website
Research Interests:
1. Regulation of gene expression.
The cystic fibrosis transmembrane conductance regulator gene (CFTR), which
when mutated causes cystic fibrosis, shows a tightly regulated pattern of
spatial and temporal expression. The molecular basis for this regulation has
not been fully elucidated but it is clear that key regulatory elements lie
outside the gene promoter. We have identified regulatory elements flanking
the gene and within introns and mapped the likely functional cores of these
elements by comparative genomics. We are investigating i) how these regulatory
elements function with the CFTR promoter, and ii) how modifications in chromatin
structure modulate expression of the gene in vivo. We are also studying the
developmental regulation of CFTR expression. These studies are of direct relevance
to CF gene therapy.
2. Mucin glycoprotein structure and function.
Mucins are heavily O-glycosylated glycoproteins that play a key role in the
human airways and are also important in the function of many other epithelia
including those lining the pancreas and intestine. Mucins may be secreted
from cells via granules or exist as membrane-tethered molecules that can be
released from the cell surface. The modifications of mucins that result in
the phenotype of CF and other epithelial diseases and are associated with
many cancers are poorly understood. We are investigating the molecular biochemistry
of membrane-tethered mucins which are co-translationally cleaved, processed
and transported to the cell-surface as dimers or multimers. Mucin release
from the cell surface, subsequent to ligand binding or other extracellular
stimuli, triggers intracellular signalling cascades. Modulation of the release
of membrane-tethered mucins may be of therapeutic benefit.