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Home > ARRA Stories > Dr. Sheri Holmen: Finding Targets for Melanoma Therapy
Dr. Sheri Holmen: Finding Targets for Melanoma Therapy

By Amber K. Boehm

April 28, 2010

Photo of Sheri Holmen

Dr. Sheri Holmen, Department of Drug Development, Nevada Cancer Institute.

Sheri Holmen, Ph.D., Assistant Professor, Department of Drug Development, Nevada Cancer Institute

Traditional mouse models rely on breeding mice in order to investigate the role of specific genes in cancer. Dr. Sheri Holmen has a new, more efficient technique: she transfers cancer genes that are under investigation directly to mouse skin cells to study melanoma. By identifying key genes, Holmen expects to find new targets for drug therapies for cancer.

The Problem: The incidence of melanoma has increased 600 percent over the last four decades, and this disease is the leading cause of cancer death in women aged 25–29. Melanoma can be easily treated if caught early, but in its advanced stages the disease rarely responds to treatment. Identifying genes that are implicated in melanoma will help scientists find new targets for therapies that will improve health outcomes.

Finding a Solution: Dr. Holmen has created a method in which specific cancer-causing genes are inserted into mouse skin cells. Dr. Holmen then studies the process of tumor formation and characterizes the roles of newly identified genes in this process. Depending on how the products of those genes affect tumor growth, a gene may be selected as a target for new drugs.

The elegant melanoma model created by Dr. Holmen more closely mimics human melanoma than do other models and allows her to test multiple genes simultaneously in a manner that is much more efficient than traditional models. The system is also more nimble; the expression of genes can be turned off to determine whether they are mandatory for continued tumor growth. Variability can be controlled, allowing target candidates to be identified.

Chromosomes showing gene amplification

Mouse chromosomes (blue) showing gene amplification (pink) during tumor progression.

How this funding helps: Dr. Holmen has expanded her research to find genes involved in the metastasis of melanoma. Her laboratory identified accelerated tumor growth in some mice, which she and her colleagues analyzed with array comparative genomic hybridization (which detects genetic insertions or deletions) and gene expression arrays (which test for changes in protein expression). She identified the spontaneous increase in the number of gene copies and overexpression of a protein typically found on the cell surface of melanocytes. By inhibiting this protein, Dr. Holmen showed that the tumors were dependent on its expression. This protein has been identified and targeted in other types of cancer, but this is the first time it has been implicated in melanoma, and it may be a potential target for melanoma therapy.

With the new ARRA funding, Dr. Holmen was able to hire a full-time research technician, Andrea Jydstrup, a recent graduate of the University of Nevada. In addition, four people joined her laboratory for continued science education through summer research programs: two community college professors from the College of Southern Nevada and two undergraduates from University of Nevada, Las Vegas and University of Nevada, Reno spent the summer of 2009 in Dr. Holmen's laboratory and will have the opportunity to return in the summer of 2010.

"With more people in the laboratory, the pace of discovery in my laboratory accelerated dramatically using a mouse model that has been successful beyond our expectations. ARRA funding has allowed us to do more, more quickly."

After Two Years … With Dr. Holmen's research model up and running, her laboratory is primed for continued discovery of therapeutic targets. Experiments using traditional methods that once took a year can now be completed in a week using the new model. Dr. Holmen will rapidly test combinations of genes implicated in melanoma and verify whether they are viable targets for therapy. Ultimately, Dr. Holmen expects that melanoma patients will have more treatment options as a result of this research.

Recovery Act Investment: "A High-Throughput Model for Human Melanoma," $208,080 for FY 2009–2010 from the Office of the Director; "A High-Throughput Model for Human Melanoma," $513,524 for FY 2009–2011 from the National Cancer Institute.

Andrea Jydstrup, Research Technician:

"When I was looking at research positions for after graduation, it seemed like nobody was hiring. My colleagues and I were very nervous about finding a job in our field, and I know a couple of my friends ended up resorting to retail or restaurant positions. I know I was incredibly lucky to find this opportunity."

Photo of Andrea Jydstrup

Andrea Jydstrup

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