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B7-H3 in Medulloblastoma: evaluating its expression and function to harness new therapeutic targets

Award Number: K08NS116651
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/15/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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B7-H3 in Medulloblastoma: evaluating its expression and function to harness new therapeutic targets - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $195,184 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/21/2024	NON-COMPETING CONTINUATION	$195,184
														Subtotal = $195,184

Issue Date FY: 2023 ( Subtotal = $195,184 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/29/2023	NON-COMPETING CONTINUATION	$195,184
														Subtotal = $195,184

Issue Date FY: 2022 ( Subtotal = $194,184 )
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	3/23/2022	NON-COMPETING CONTINUATION	$194,184
														Subtotal = $194,184

Issue Date FY: 2021 ( Subtotal = $194,184 )
2021	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/17/2021	NON-COMPETING CONTINUATION	$194,184
														Subtotal = $194,184

Issue Date FY: 2020 ( Subtotal = $194,184 )
2020	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/10/2020	NEW	$194,184
														Subtotal = $194,184

Grand Total All Awards = $972,920

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B7-H3 in Medulloblastoma: evaluating its expression and function to harness new therapeutic targets

Award Number: K08NS116651

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/15/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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