Primary and metastatic brain tumors represent unique clinical challenges and often confer poor prognosis. Our research program is focused on understanding the mechanisms that drive these tumors such that vulnerabilities can be identified and therapeutically exploited. To this end, we have generated novel mouse models that not only validate the role of specific genes in tumor formation but also assess whether they are required for tumor progression and/or maintenance. High-throughput sequencing efforts have yielded an abundance of information in many cancer types. In both low grade gliomas and high grade secondary glioblastomas, a common point mutation in the metabolic gene isocitrate dehydrogenase (IDH) was identified. While these findings represented a significant breakthrough in this disease, a role for IDH in the etiology of these tumors was unclear and whether mutant IDH or products of its activity could be productively targeted for therapeutic intervention had yet to be determined. Using our unique mouse model, we demonstrated that mutant IDH is a bona fide oncogene and its oncogenic effects are mediated through its production of the oncometabolite 2-hydroxyglutarate. Likewise, analysis of melanoma patient samples revealed high levels of AKT activation in brain metastases as compared with other sites of disease. We validated this in our melanoma mouse model and demonstrated that the mechanism by which activated AKT promotes melanoma brain metastasis is through activation of proteins involved in focal adhesions. Our work has made a significant impact in these fields and has the potential to improve outcomes for patients with these cancers.
Sheri Holmen, PhD, wished to make an impact on the lives of people experiencing cancer and found that becoming a researcher would allow her that and more. When she's not in her lab, Dr. Holmen will often spend time with her children in their many athletic activities, which led her to become nationally certified to officiate swim competitions. Learn this and more in this edition of Talks with Docs.... Read More
The Society for Melanoma Research recently presented Sheri Holmen, PhD, with the prestigious Estela Medrano Memorial Award. Holmen is a melanoma researcher at Huntsman Cancer Institute and a professor of surgery at the University of Utah. This award was created in honor of the late Estela Medrano, a leader in melanoma research. The Estela Medrano Award is given annually to a woman who has made major contributions in the fight against melanoma.... Read More
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Gliomas are the most common type of central nervous system cancer but how these tumors develop is not fully understood. Sheri Holmen, PhD a researcher at Huntsman Cancer Institute and professor of surgery at the University of Utah just published the results of her research on gliomas in Cell Reports. The work is focused on a mutated gene that is a critical piece of the puzzle for glioma development, according to Holmen’s work.... Read More
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