Project Details
Description
PROJECT SUMMARY/ABSTRACT
This proposal outlines a 5 year career development program designed to further my research program into the
function and potential therapeutic utility of immune checkpoint molecules in the pediatric brain tumor,
medulloblastoma (MB), the most common malignant brain tumor in children. As a pediatric neuro-oncologist, I
am passionate about finding novel therapies for the ~25% of children whose tumors do not respond to
standard treatment and have no cure. This proposal builds on my previous research evaluating the expression
of PD-L1 in MB and generating a syngeneic animal model of MYC-driven anaplastic MB that mimics recurrent
disease. I previously found that there was a paucity of PD-L1 expression in MB and thus far clinical trials of
antibodies targeting this pathway have not met with significant success. Therefore, I moved my research
program from Johns Hopkins University to Albert Einstein College of Medicine (AECOM)/Montefiore Medical
Center (MMC) for the opportunity to work with my mentor, XingXing Zang, PhD on the novel B7 family immune
checkpoint molecule, B7-H3, which is highly expressed in MB and represents an attractive therapeutic target.
The scientific objective of this proposal is to evaluate the efficacy of B7-H3 blocking antibodies as a treatment
for MB and lay the preclinical foundation for a future clinical trial. To accomplish this, I will study B7-H3 in my
murine MB model as well as in classic human MB cell lines, and human MB patient samples. These studies
stem from published literature reporting B7-H3 in human MB and my own preliminary data demonstrating its
expression in my model. I will have strong support from my mentor, Dr. Zang, who has developed the
translational B7-H3 blocking antibodies for this study as well as tools to knock down B7-H3 in the tumor and in
the infiltrating immune cells. The purpose of this project is to both complete my scientific aims and to provide
me with the additional knowledge and skills to launch a fully independent pediatric brain tumor research
program. I will increase my immunology and neuroscience knowledge by participating in graduate courses and
interacting with Dr. Zang an immunologist, and my co-mentor, Emad Eskandar, MD, a neuroscientist. I will
obtain new skills important to the completion of this project that will also serve me in future research endeavors
including the generation of bone marrow chimeric mice, and the analysis of single-cell RNA-seq data. I will
participate in genomics and bioinformatics courses to familiarize myself with genomics techniques and learn
the proper biostatistical methods to interpret them. These important skills will lay the foundation for my future
an independent physician scientist.
Status | Finished |
---|---|
Effective start/end date | 4/15/20 → 3/31/24 |
Funding
- National Institute of Neurological Disorders and Stroke: $195,184.00
- National Institute of Neurological Disorders and Stroke: $194,184.00
- National Institute of Neurological Disorders and Stroke: $194,184.00
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.