The UC Santa Cruz Colligan Clinical Diagnostic Laboratory (CCDL) has received its CLIA certificate of registration from the California Department of Public Health, which clears the way for it to begin accepting patient samples.
The CCDL team will use a newly clinically validated test that they have developed to analyze patient samples for abnormalities in their RNA that could identify life-saving treatment options, particularly for pediatric cancer patients.
“Our team is exceedingly motivated by the power of our specialized analysis,” said the lab’s technical supervisor, Professor of Molecular, Cell, and Developmental Biology Olena Vaske. “In the next ten years, we hope that this analysis can be offered to every pediatric patient, so that during one of the most difficult periods of their lives, more families will be able to hear someone say, ‘we know exactly what this is and how to treat it.’”
The CCDL is a part of the Genomics Institute’s Treehouse Childhood Cancer Initiative, which was founded in 2015 by Vaske, Genomics Institute Scientific Director David Haussler, and a team of dedicated staff to create innovative new tests for identifying treatment options for pediatric cancer patients.
“This is a huge milestone in what has been a multi-year effort to create a certified clinical lab on the UC Santa Cruz campus,” said Lauren Linton, Executive Director of the UC Santa Cruz Genomics Institute. “Creating a clinical lab from scratch was a big lift, but the Genomics Institute has seen how incredibly transformative our RNA analyses can be for patients, and we knew that we had to make every effort to get it into the hands of more physicians. Our ultimate goal is to revolutionize the standard of care offered to all pediatric cancer patients, and this is a giant leap forward. I am extremely proud of the broad community of researchers, funders, and staff who made this possible.”
While many cancers are still initially classified based on their location in the body (e.g. liver cancer, lung cancer, etc), scientists and clinicians now know that cancers are actually better understood on a molecular level. Two patients with cancers in the same location might have subtly different types of cancers that may respond differently to the same treatment.
Genetic testing of tumors has helped to identify a number of new treatment options for patients, but these tests look at patient DNA, and are often not helpful in identifying the drivers of pediatric cancers. This is because mutations in the DNA usually develop over time, and are therefore more common in adults. Childhood cancers, on the other hand, are more often caused by irregularities in gene expression that can only be seen once the DNA is transcribed into RNA.
Treehouse has developed a unique type of analysis for RNA called the Comparative Analysis of RNA Expression (CARE), which they are able to use to identify druggable over-expressed genes and pathways. In a past study performed by the team that looked at 144 tumor samples, they observed that DNA mutation information was potentially useful for finding druggable options in only 46% of the samples, whereas the CARE analysis was potentially useful for 68% of the same samples. However, because the CARE test was not yet clinically validated, doctors were only able to use it for critically ill patients who had no other treatment options.
“Having a clinical lab, and a clinically-validated test, will enable us to provide analyses for more patients earlier in the course of their treatment,” Vaske said. "We are very hopeful that it will save lives by identifying druggable pathways for treatment that would otherwise be missed, but it will also save patients from undergoing multiple rounds of harsh chemotherapy drugs only to find out that they aren’t effective for their specific cancer type.”
The first CCDL clinical test that will be implemented on patient samples identifies the presence of gene fusions in patient RNA. Gene fusions are genes that have been joined together due to rearrangements of the DNA. While some can be harmless, other fusions get transcribed into RNA that produces faulty proteins, which are known to be involved in certain cancers.
The Treehouse research and development team is also working on developing other novel tests that will look at tumors to see if genes are being over-expressed in the RNA. This test would be brand new, with no equivalent currently on the market. This may provide a wealth of new information about difficult-to-treat cancer types.
Vaske will be the Technical Supervisor of the lab under the supervision of the group’s long-time collaborator and CCDL Medical Director Patrick Devine, who is an Associate Professor of Pathology and Medical Director of the Clinical Cancer Genomics Laboratory and Genomic Medicine Laboratory at UC San Francisco. Treehouse Lab Manager Anouk van den Bout runs the Treehouse wet lab, and has led the effort to obtain clinical licensing.
“I have had the good fortune of having tremendously dedicated people help drive the Treehouse program. Former Treehouse Director Isabel Bjork set the foundation for a clinical laboratory to offer our tests to patients. Isabel dreamed that a clinical genomics lab at UCSC was possible, even when it was unclear how to proceed,” Vaske said. “Then Anouk Van den Bout joined us, and with her vision, incredible attention to detail, we forged forward. Anouk really led this effort, and I am so grateful to her,” Vaske said.
Van den Bout helped Treehouse navigate a very complex regulatory process.
“Building a clinical lab on a research campus without the infrastructure from an existing medical institution was especially challenging, Van den Bout said. “There were many hurdles to overcome to meet federal requirements, all while developing our complex next-generation RNA sequencing test.”.
Van den Bout first came to UC Santa Cruz as a visiting scholar in 2015, then became committed to the Treehouse mission and decided to stay. When the pandemic hit, she co-led the UC Molecular Diagnostic Laboratory SARS-CoV-2 testing efforts founded with a generous gift from local philanthropists Bud and Rebecca Colligan. The group built a clinical-grade testing facility to be used for the pandemic, with the goal to later transition into a diagnostic lab for pediatric cancer. At its height, the lab processed 5,000 COVID-19 tests a week, and they were honored with the 2021 Phil Rather Award for Leadership in Healthcare and a Santa Cruz Works Hometown Heroes Award for their service to the community.
As the pandemic wound down, and the pandemic-driven regulatory relaxations that allowed CCDL to operate in the clinical diagnostic space were removed, Van den Bout began working on the complex process to get the lab licensed to again run clinical samples. Van den Bout was motivated by her belief in the unique strength of the Treehouse team to create and validate a powerful clinical test.
“It was very exciting to develop the wet lab component of our test in coordination with the Treehouse dry lab team,” Van den Bout said. “During this process you could really see the strength of our combined multidisciplinary knowledge at work.”
Next Steps for the CCDL
Now that the CCDL has their CLIA certification, they anticipate that they will be up and running and accepting patient samples within a few months. They will start processing approximately six patient samples a week until they are able to expand their team. These samples will initially come from their partners at UCSF, but in the near future, they plan to accept blood and tissue samples from other medical facilities.
“The potential of the Colligan Clinical Diagnostic Lab to help families who are facing pediatric cancer is truly incredible,” said UC Santa Cruz Chancellor Cynthia Larive. “Having a clinical lab at UCSC is also a huge benefit to the campus and local community. As the lab launches into cancer treatment precision medicine, it will allow our campus to extend our impact in the health fields, provide training opportunities for students, and open the doors for new collaborations, particularly as the campus plans for the expansion of health-related programs. I am very proud of the entire team for this tremendous accomplishment.”
The next step for the lab will be to get accredited by the College of American Pathologists (CAP), which will inspect the lab once they start running patient samples. With this accreditation, the team will validate a more expansive RNA test that will incorporate a combination of quantitative and qualitative assessments to identify more druggable pathways and help more patients.
“We worked very hard to develop our clinic-ready high-complexity test,” Vaske said. “Our work has already made a difference for children and their families affected by cancer. We still have a long way to go to get to where we can offer it to every patient with pediatric cancer, but this is a big step towards meeting our ultimate goal.”
Numerous funders and partners have made this lab possible. The Treehouse team would like to thank Unravel Pediatric Cancer for being their first funder, as well as Bud and Rebecca Colligan, Ted Goldstein, and Jessica Bernhardt for their generous and unwavering support over the years. Treehouse has also received funding from the St. Baldrick’s Foundation, California Initiative to Advance Precision Medicine (CIAPM), the Genomics Institute Healthier World Fund, Emily Beazley Kures for Kids Fund, American Association for Cancer Research, National Cancer Institute, Alex's Lemonade Stand Foundation for Childhood Cancer Research, Live for Others Foundation for Childhood Cancer Research, UC Cancer Research Coordinating Committee, Team G Childhood Cancer Foundation, and numerous private donors.
This effort would not have been possible without pediatric oncologists and clinical researchers, including Sheri Spunt (Stanford University), Alejandro Sweet-Cordero and W. Patrick Devine (UC San Francisco), Analiz Rodriguez (University of Arkansas Medical Service), Bang Hoang (Albert Einstein School of Medicine), Rod Rassekh and Elizabeth Deyell (BC Children's Hospital), Elaine Mardis (Nationwide Children's Hospital), Allie Pribnow and Norman Lacayo (Stanford University), Sabine Mueller (UC San Francisco), Aru Narendran (University of Calgary), and Leonard Sender (Children's Hospital of Orange County). This effort was also supported by numerous pediatric cancer advocacy partners, especially Jacob's Heart Children's Cancer Services.
The entire Treehouse team participated in the effort, with key contributions from current members Holly Beale, Ellen Kephart, Geoff Lyle, Yvonne Vasquez, and Elise Huang, as well as alumni and past advisers Katrina Learned, Molly McCabe, Jolene Draper, Kathryn Echandia-Monroe, Isabel Bjork, Ted Goldstein, Branwyn Wagman, and Sofie Salama. The UCSC Vice Chancellor for Research, John Macmillan, has been an invaluable supporter of the Treehouse program.
