# Integrative Molecular Epidemiology of Neurocognitive Outcomes in Acute Lymphoblastic Leukemia

> **NIH NIH K07** · BAYLOR COLLEGE OF MEDICINE · 2021 · $150,823

## Abstract

Project Summary/Abstract
This K07 Career Development Award proposal details the rigorous training, research, and mentorship program
that will provide a foundation for Dr. Brown to launch a successful independent research career. Dr. Brown’s
long-term career goal is to establish a productive independent research program, with an emphasis on
identifying novel biomarkers and modifiable therapeutic targets to reduce the burden of treatment-related
toxicity among pediatric cancer patients. Therefore, the research goal for this proposal is to characterize early
phenotypic, metabolomic, and genomic biomarkers of chemotherapy-associated neurocognitive impairment in
pediatric acute lymphoblastic leukemia (ALL) patients. Although improved treatment regimens for pediatric ALL
have resulted in survival rates exceeding 90%, nearly half of patients experience chronic treatment-related
neurocognitive dysfunction. This proposal pursues the hypothesis that central nervous system-directed ALL
chemotherapy disrupts the equilibrium of cerebral spinal fluid (CSF) metabolome, manifesting as acute
symptom toxicity and long-term neurocognitive dysfunction. Because genetic factors likely control the CSF
metabolomic response to therapy, we further hypothesize that integrating genetic and metabolomics data will
lead to the discovery of causal genetic pathways. The specific research aims of this proposal will evaluate
whether: 1) Symptom toxicity during the post-induction phase of ALL therapy reflects chemotherapy-directed
neurologic damage and serves as an early marker of post-treatment neurocognitive performance; 2) ALL
chemotherapy induces consistent and recognizable changes to CSF metabolomic pathways involved in normal
neurocognitive function and development; and 3) Genetic variation modifies individual susceptibility to
neurocognitive impairment. Leveraging two NIH-funded studies with rich phenotype data and biospecimen
repositories, this innovative proposal will establish one of the largest prospective investigations of
neurocognitive outcomes in pediatric ALL patients. The research experience gained during the course of this
study complements the proposed career development goals. Specifically, didactic training and interaction with
experienced mentors in molecular epidemiology (Dr. Scheurer), symptoms research (Dr. Hockenberry),
metabolomics (Dr. Devaraj), and neuropsychology (Dr. Ris) will enhance Dr. Brown’s: 1) Content area
expertise in patient-reported symptoms and neurocognitive evaluation; 2) Understanding of metabolomics
research methods; and 3) Proficiency in grant and scientific writing. The comprehensive career development
and research plan outlined in this proposal will address key gaps in Dr. Brown’s training, provide additional
research experience, and serve as a unique resource of preliminary data to support future research endeavors.

## Key facts

- **NIH application ID:** 10119256
- **Project number:** 5K07CA218362-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Austin L Brown
- **Activity code:** K07 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $150,823
- **Award type:** 5
- **Project period:** 2018-04-11 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119256

## Citation

> US National Institutes of Health, RePORTER application 10119256, Integrative Molecular Epidemiology of Neurocognitive Outcomes in Acute Lymphoblastic Leukemia (5K07CA218362-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10119256. Licensed CC0.

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