Two early-career scientists at Fred Hutchinson Cancer Research Center have received prestigious grants to further their prostate cancer research.
Alexandra “Alex” Corella, a graduate research assistant, won a $25,000, one-year fellowship from the Ford Foundation Fellowship Programs, which are administered by the National Academies of Sciences, Engineering and Medicine. She will use the funding to complete her doctoral dissertation research on small-cell neuroendocrine prostate cancer, or SCNPC, an aggressive malignancy that doesn’t respond well to conventional therapies.
“I am very excited and grateful to be receiving the Ford Dissertation Fellowship, which will provide support in my final year of my Ph.D. and will open doors for me in the next stages of my career,” said Corella, one of 38 dissertation fellowship recipients this year.
Dr. Sander Frank, a postdoctoral research fellow, received a three-year training fellowship of more than $210,000 from the National Institutes of Health to study how mutations in genes that control DNA repair promote tumor progression and whether these mutations may be exploited for targeted therapies. The NIH established the Ruth L. Kirschstein National Research Service Award for Individual Postdoctoral Fellows, otherwise known as an F32 award, to help postdocs transition to independent research careers.
“I am grateful to receive a highly competitive F32 fellowship and am thrilled to be part of a very supportive prostate cancer research group at the Hutch,” Frank said. “Over the next three years, I will be able to continue my professional development and work on a great research project that will hopefully lead to new therapy options for prostate cancer patients in the future.”
Both Corella and Frank work in the laboratory of Dr. Peter Nelson, who holds the Endowed Chair for Prostate Cancer Research at Fred Hutch. Nelson co-leads the center’s multidisciplinary Program in Prostate Cancer Research. Frank is co-mentored by Dr. Valeri Vasioukhin, whose Fred Hutch lab studies model systems of prostate cancer progression.
Corella, who is completing her doctoral research through an interdisciplinary molecular and cellular biology Ph.D. program offered through Fred Hutch and the University of Washington, is particularly interested in the mechanisms that enable SCNPC to grow and thrive within the body, impervious to standard treatments for metastatic disease, such as androgen-blocking therapy. Such mechanisms have remained elusive due to the rarity of the disease — it accounts for about 17 percent of advanced prostate cancer cases — and a lack of model systems with which to study it.
Already she has analyzed RNA-sequencing data from a panel of aggressive, small-cell neuroendocrine tumors — not only from the prostate but also from a rare, aggressive skin cancer called Merkel cell carcinoma and from small-cell lung cancer tumors. She has found that although these neuroendocrine cancers arise in different parts of the body, they share some 4,300 genes in common. She then analyzed these genes to see which ones may contain potentially “druggable” mutations that would respond to treatment.
Corella has identified one such mutation, BCL2, which is highly expressed in patients with SCNPC and other neuroendocrine cancers. She plans to devote the next phase of her dissertation research investigating the biology of BCL2’s role in aggressive prostate cancer.
Frank joined the Nelson and Vasioukhin labs in 2018 and is interested in understanding the role of DNA-repair gene mutations in prostate cancer. Genes in the DNA-repair pathway were recently found to be mutated in about 20% of advanced prostate cancers. Frank will use a combination of lab-grown cell lines and mouse models to test precisely how loss of three key DNA-repair genes (BRCA1, BRCA2 and CDK12) can promote cancer progression and potentially sensitize tumors to certain therapies.
In the Vasioukhin Lab, Frank has helped generate mice with prostate-specific gene deletions to study how knocking out these genes affects prostate cancer development. In the Nelson Lab, he is working with cell lines and patient-derived xenograft models, in which human tumors are grown and tested with drug treatments in mice. The loss of DNA-repair genes such as BRCA1/2 is known to sensitize other cancer types to targeted therapies that exploit faulty DNA repair in tumors and overload them with DNA damage. Frank will use this combination of models to test potential therapies against prostate cancers with DNA-repair loss and determine which strategies and combinations would be most effective against prostate cancer.
Kristen Woodward, a former associate editor at Fred Hutchinson Cancer Research Center, had been in communications at Fred Hutch for more than 20 years. Before that, she was a managing editor at the University of Michigan Health System and a reporter/editor at The Holland Sentinel, a daily in western Michigan. She has received many national awards for health and science writing. She received her B.A. in journalism from Michigan State University.