Kevin R. Krull, PhD

The trajectory of brain development can be altered and negatively affected by the cancer itself and the chemotherapy and radiation required to treat it. Understanding the mechanisms that alter the developmental trajectory is critical to forming effective and specific interventions that may lead to a higher quality of life. Our research follows patients from diagnosis through older adulthood and aims to identify mechanisms underlying alterations in brain development and reserve. With more information about these underlying mechanisms, we work to enhance interventions that improve survivor outcomes.

As part of the Department of Epidemiology and Cancer Control and the Department of Psychology and Biobehavioral Sciences, my colleagues and I conduct multidisciplinary research that involves both characterization and interventional approaches. Our characterization work, conducted primarily for patients with leukemia and lymphoma, assumes a biological, psychological, and social perspective as we study direct action within the brain. Through this approach, we examine biomarkers in the cerebrospinal fluid and assess brain imaging as well as cognitive function. Because brain function is influenced by cardiopulmonary, endocrine, inflammatory, and other processes throughout the body, we take a comprehensive whole-body approach to comprehend how these processes impact the brain. Our comprehensive approach provides the necessary information to develop more precise and targeted interventions. 

Along this line of research inquiry, we work with the Center for Proteomics and Metabolomics to conduct a full proteomic characterization of the cerebrospinal fluid prior to and throughout treatment in patients who have leukemia. This characterization identifies proteins that associate with the integrity of glial cells and astrocytes as well as the structure and integrity of neurons and many processes in the central nervous system (CNS). Using mass spectrometry, we can identify more than 2,000 proteins and determine which elements impact CNS integrity and are associated with long-term brain development.

Our intervention work involves enhancing health behavior and direct brain stimulation. Improved health behaviors, like sleep and physical activity, can support brain development and function. We also use an approach called neuromodulation, an example of which involves the use of electrodes on the surface of the head to modulate neural activity with low levels of electrical stimulation. We conduct transcranial direct-current stimulation as well as transcranial alternating current stimulation, depending on where a patient’s deficit is located in the brain. This type of neuromodulation lowers the threshold for the brain to function, allowing us to engage affected areas more easily. Using this approach, a patient can engage in a cognitive task (like practicing memory skills) to fine tune the brain’s network to an improved functional state. We also employ a process called photobiomodulation, which uses a near-infrared light that penetrates the skull to decrease inflammation and oxidative stress to help improve overall brain function. 

The improvement of neurological development and cognitive function in patients and survivors of childhood cancer is a driving force for our work. By understanding how and why these neurocognitive effects occur, we hope to contribute to interventions that increase quality of life.