Professor
Regulation of gene expression by growth factors in animal cells
Imaging of gene expression in vivo
Applications of aptamers to medical technology
Growth factors regulate proliferation and cellular activities
that result in coordinated growth and differentiation of animal tissues.
To achieve their effects, growth factors regulate gene expression and
thus the production of new proteins. Proteins that are secreted are
often involved in coordinating cell growth in multicellular tissues.
Dr. Nilsen-Hamilton has discovered several secreted proteins and their
genes that are regulated by growth factors. The research team is exploring
the means by which these genes are regulated by growth factors.
The group discovered a unique fibroblast growth factor response element
(FRE) in the mrp3 gene promoter. The FRE is also found in the promoters
of many metalloproteinases that are important for cancer cell movement
during metastasis. They have also found that the mrp/plf genes are expressed
during wound healing and also in some fetal tissues. Mrp3 is the main
mrp/plf that is expressed in the wound.
Uterocalin is another secreted protein that is regulated by growth factors.
It is an acute phase protein, produced by the liver, lungs and other
epithelial tissues in response to stress such as occurs with infections.
Uterocalin is also produced by the uterus around birth and in the mammary
gland during involution after the young have stopped suckling. The protein
is a lipocalin and may be involved in protection from infections by
microbes during reproduction. A higher expression of this gene is also
correlated with protection against breast cancer. The group is studying
the protein's function and how the gene is regulated.
To understand how growth-factor-induced genes are regulated and to identify
the physiological functions of the protein products, Dr. Nilsen-Hamilton
and her group are using biochemical, molecular, cellular, and developmental
approaches, which include purifying the proteins, cloning the genes,
determining their sequences, identifying the relevant regulatory elements,
and identifying new transcriptional regulators. They are using cell
cultures to express the proteins and also as "reporter" systems
to study the activity of the regulatory elements of each gene. Studies
of the regulation of gene activity also involve functional in vitro
assays such as the electrophoretic mobility shift assay for transcription
factors and in vivo studies of the levels of expression of the gene
under different physiological conditions.
In fighting almost any disease the ability to detect and treat it in
the early stages is critical to a successful outcome. For most diseases
there are changes in gene expression and subsequent protein products
that could be used for early detection.
However, disease-initiated changes often occur in the depths of our
tissues. Therefore a challenge for developing new technology to fight
disease is to find ways of non-invasive imaging (e.g. no biopsy or surgery)
of the body’s status.
