Shared Resources Spotlight: Clinical Biomarkers Laboratory

Learn more from less. That turn on a common phrase encapsulates some of the latest challenges and successes from the St. Jude Clinical Biomarkers Laboratory (CBL). CBL is a shared resource within the Department of Pathology that helps researchers at St. Jude conduct correlative scientific studies related to clinical trials. Grounded in the values of collaboration and sharing expertise, the CBL staff partner with investigators to make the most out of the resources and data gathered through clinical research.  

CBL is involved in research through the entire project lifecycle, from method selection, development and validation to protocol design and data delivery and analysis, among other aspects. The team’s work includes developing custom immunoassays to better understand specific sets of proteins, as well as performing nucleic acid extractions and genomic testing to study and monitor a range of diseases. 

“Our scientists are experts in designing and facilitating research studies with patient samples,” said Ruth Tatevossian, MBBS, PhD, CBL director since 2014. “That includes molecular, genomic, metabolomic and immunological testing.”

With advanced biomarker testing available on site, St. Jude clinical researchers receive more personalized, cost-effective service than they would with an external lab, with results typically delivered weeks to months faster.

“I’ve worked with a variety of labs over the past 20 years, including private labs as well as collaborators that I know,” said Kevin Krull, PhD, Department of Psychology and Biobehavioral Sciences chair. “We were able to move that work into St. Jude with the development of the Clinical Biomarkers Lab. Other institutions aren’t as invested in our success as our St. Jude colleagues.”

Pioneering new approaches in the CBL 

The researchers who work in the CBL strive to customize tests and pioneer new techniques that help them learn more from smaller or fewer samples. These efforts expand research possibilities while often making participation easier for pediatric patients. 

Giles Robinson, MD, Division of Neuro-Oncology director, leveraged the CBL to extract DNA from formalin-fixed paraffin-embedded (FFPE) tissue. FFPE is the most common available specimen for brain tumor research, but retrieval of genetic material from these samples is tedious due to prolonged formalin fixation. To make use of a new technology called methylation profiling, Robinson needed to extract high-quality DNA from these samples. The CBL was not only able to extract the DNA but also to do it at scale from over a thousand samples. Robinson and the team have since used methylation to establish a new risk stratification for patients with medulloblastoma. The knowledge gained enables pediatric oncologists to tailor treatment accordingly.

“I can now design trials based on the patients’ methylation profiles, and because of CBL’s work, we have also been able to make methylation profiling a clinical test,” Robinson said. “So, when a patient is diagnosed with a brain tumor, they get clinical methylation here at St. Jude, and we can make the intricate molecular diagnosis that we now need to treat these patients.”

Pioneering cell-free DNA analysis

Looking ahead, Robinson said blood samples collected during a trial for an MEK inhibitor in patients with low-grade glioma will be sent to the CBL, where they will look for circulating tumor DNA. The project correlates with other research the CBL is conducting around cell-free DNA (cfDNA) and liquid biopsy, which provides an alternative to more invasive tissue biopsy or a bone marrow aspirate test.

A liquid biopsy is a simple blood draw that uses leading-edge technology to detect cfDNA. cfDNA includes both circulating tumor DNA from cancer cells and fragmented DNA floating freely in the blood.

In 2024, a team that included Jeff Klco, MD, PhD, Charles Mulligan, MBBS (Hons), MSc, MD, and members of the CBL Shared Resource published a paper in the journal Blood, that explored how researchers can use cfDNA as a diagnostic tool. 

“This is a new and exciting field in cancer research,” said Tatevossian. “cfDNA was initially used for fetal diagnostics. Now we’re applying that technology to cancer detection and monitoring treatment response.” Sujuan Jia, PhD, a senior scientist with the CBL, is testing cfDNA methods to bring liquid biopsies into clinical trials for solid tumor and leukemia patients.

Another area of growth for the CBL is targeted mass spectrometry, which is used to analyze proteins and small molecules, especially those that are difficult to test using antibody-based methods. 

“Assays we weren’t able to do reliably with commercially available methods can now be done with mass spec,” said Seba Mahapatra, PhD, a senior scientist with the CBL “This method has a high sensitivity that will allow us to do more with a small sample and customize assays to whatever the investigator needs.”

Sleep study moves forward with guidance from CBL

Mahapatra is currently using mass spec to work through approximately 900 blood spot samples collected for a study led by Krull and Tara Brinkman, PhD, Departments of Psychology and Biobehavioral Sciences and Epidemiology and Cancer Control. Called SLEEPWELL, the randomized clinical trial was designed to examine the efficacy of an internet-based cognitive behavioral therapy (CBTi) program for improving insomnia symptoms in long-term childhood cancer survivors. While the trial’s primary objective is to study the efficacy of the CBTi program, researchers also wanted to learn more about how sleep impacted neurocognitive function, cardiovascular health and emotional stress.

The researchers initially planned to hire home health aides to collect patients’ blood samples. However, COVID-19 hit the United States right when the study was scheduled to start. Home visits were no longer an option. As an alternative, the team found a validated method to measure cognitive function remotely, requiring patients to collect samples themselves using blood spot cards. To ensure patients understood how to collect their samples, the team provided patients with a web link to a video demonstration they had developed.

At CBL, Mahapatra designed custom assays to measure biomarkers from the blood spot cards. As a result of CBL’s work on the project, the researchers have found they can assess some of the initially planned proteins related to inflammation, oxidative stress and cardiovascular health. Mahapatra is running the CBL’s first targeted mass spec assay, which was specifically developed for the SLEEPWELL study. Overall, the work provides a validated procedure that researchers can use for future studies. 

Collaboration across teams drives success

Whether creating custom tests, bringing new techniques to St. Jude, or solving study problems through creative design and adaptations, Tatevossian and the CBL team are instrumental collaborators for clinical researchers at St. Jude.

“We focus on a specific niche for clinical investigators,” she said. “Some have robust science backgrounds and know how they want to approach a research question. Others may not, but they still have really interesting questions. By partnering with St. Jude scientists, we can help them answer those questions.”