5 Questions for Layne Pullen

This question-and-answer series explores the Preclinical Therapeutics Program at St. Jude through the lens of Layne Pullen, a researcher within the program. Pullen graduated from Mississippi State University with a BS in Veterinary Medical Technology and worked at a veterinary specialty practice in Memphis for six years before transitioning to her current position.

1. What is the role of the Preclinical Therapeutics Program?

The Preclinical Therapeutics Program assists investigators with designing and executing preclinical studies with the goal of discovering more effective therapies to treat children with cancer. We are a group of five researchers and three research program managers, led by Elizabeth Stewart, MD, Department of Oncology, within the St. Jude Comprehensive Cancer Center, who focus on special animal health observations, bioluminescent imaging, sample collection, treatment administration and other technical procedures for preclinical trials. A key facet of our program is that our approach is tailored to whatever the investigator needs for their study.

2. How does the Preclinical Therapeutics Program collaborate with investigators to support preclinical studies?

The Preclinical Therapeutics Program is subdivided into three separate programs: the Developmental Biology and Solid Tumor Program, the Hematological Malignancies Program, and the Neurobiology and Brain Tumor Program, which is the program where I work. Investigators come to us with ideas about what they want to accomplish, and our program managers review these proposals to make sure they are ready for preclinical studies. After the investigators and program managers settle on a study plan, researchers like me execute the plan by running experiments.

Depending on the frequency with which we work with specific investigators, we will proactively plan for studies stretching into the future. But many investigators at St. Jude are not yet fully aware of our capabilities, or that a dedicated program exists to support preclinical research at St. Jude, so we want to ensure we are consistently engaging with research groups across the institution.

3. At what stage in their project should investigators engage the Preclinical Therapeutics Program?

Engagement is flexible and can occur at multiple stages of a project. There are no rigid prerequisites, but the level of involvement depends on the maturity of the investigator’s work and their specific needs. For investigators newer to translational studies, engagement often begins with exploratory discussions. These investigators may reach out with broad questions about designing or implementing preclinical studies or may seek guidance on how to kickstart initial concepts. More established laboratories often approach us at a later stage, particularly when they are transitioning from discovery-based work toward translational applications. In these cases, investigators often present candidate therapeutics and seek support in developing and executing preclinical studies. In both cases, we serve as a collaborative partner, helping investigators refine their approach, design appropriate tests and translate their findings into practical, preclinical results that support further investigation.

4. What are the steps to preclinical therapeutic evaluation?

It depends on the investigator’s starting point and the extent of existing knowledge about the candidate drug or therapy. In some cases, evaluation begins with studies to assess drug distribution, activity and target engagement. These early findings can inform compound relevance; for example, drugs that do not effectively cross the blood-brain barrier may not be suitable for the Neurobiology and Brain Tumor Program but may remain viable for other disease areas.

If initial results are favorable, subsequent studies assess toxicity and tolerability to determine whether the compound can be safely administered without inducing significant secondary effects.

Following these safety evaluations, efficacy studies are conducted to measure the therapeutic impact on the disease. These studies are particularly informative, as they allow for real-time assessment of treatment response through imaging and dosing workflows. I find this stage to be the most exciting, as it provides a direct view of a therapy’s potential and its progression toward clinical application in patients.

5. How has the Preclinical Therapeutics Program contributed to the development of therapies at St. Jude?

Success for us is when our projects are translated into clinical trials. One example is SJiMB21, a clinical trial that is currently recruiting patients. SJiMB21 introduces stratified dosing of chemotherapy and radiation to patients with types of medulloblastoma called Group 3 and Group 4. We also worked with dasatinib to treat pediatric T-cell acute lymphoblastic leukemia (T-ALL), an approach that was recently used in the RAVEN relapse clinical trial, as well as SJALL23T for patients with newly diagnosed T-ALL. Additionally, if we comprehensively study a drug that doesn’t work well in preclinical studies, that can also be considered a success — especially if we spare kids exposure to something that is unlikely to help their disease but may only cause unwanted side effects.

When I consider how the Preclinical Therapeutics Program has impacted pediatric healthcare, it is an honor to know that what we’re doing is making such a big difference. Even one child’s life is very significant, and I’m proud to be part of a program that has such an impact on so many lives.