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MRI-guided focused ultrasound to enhance ME3BP7 delivery as a novel therapy for Glioblastoma

Award Number: K08NS140637
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 03/06/2026
PERIOD OF PERFORMANCE END DATE: 02/28/2031

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MRI-guided focused ultrasound to enhance ME3BP7 delivery as a novel therapy for Glioblastoma - Project Summary I am an Assistant Professor of Neurosurgery at Johns Hopkins, and my clinical practice focuses on brain tumors. I am applying for a mentored surgeon-scientist research career development award to gain advanced training in molecular biology, cancer metabolism, and novel drug delivery strategies to the brain. Glioblastoma (GBM) is a devastating brain cancer with a median survival of just 13 months. Challenges in treatment are largely due to tumor heterogeneity and the impermeability of the blood-brain barrier (BBB). Current treatments offer limited efficacy, necessitating innovative approaches to improve drug delivery and targeting. My project addresses this critical need by leveraging MRI-guided focused ultrasound (MRIgFUS) to transiently disrupt the BBB, enhancing the delivery of ME3BP7, a novel, stable pyruvate analog that targets MCT1, a metabolic transporter overexpressed in over 80% of GBMs. The Specific Aims of the proposal are to: (1) Elucidate the mechanism of action of ME3BP7 in GBM, focusing on its impact on MCT1-dependent metabolism and resistance pathways, and (2) to optimize ME3BP7 delivery across the BBB using MRIgFUS in patient-derived xenograft models. These experiments will validate the potential of MCT1 targeting with ME3BP7 while pioneering a clinically translatable approach for BBB disruption. As a neurosurgeon interested in translational research, I have extensive experience in cancer cell biology, orthotopic murine GBM models, and biomarker-driven drug development, including the successful design and preclinical validation of ME3BP7 in pancreatic cancer models. This K08 proposes building upon my cancer research and drug development postdoctoral training towards a new direction at the interface of metabolic targeting and translational therapeutics. Under the mentorship of Dr. Chetan Bettegowda, an internationally recognized leader in brain tumor research, I will refine my expertise in GBM metabolism, molecular biology, and drug delivery. Specific training goals include: (1) Hands-on training in molecular biology techniques, including CRISPR-Cas9 gene editing and metabolic enzyme quantification; (2) Didactic and experimental training in cancer metabolism, with a focus on metabolic flux analysis; (3) Advanced training in pharmacokinetics and drug delivery, particularly in MRIgFUS for BBB disruption; (4) Formal coursework in biostatistics, grant writing, and research ethics to strengthen scientific rigor and independence. We have created a high-quality educational and mentorship plan to complete this research with a multidisciplinary team of collaborators to help develop my career as an independent clinician-investigator. My scientific advisory committee will also support my overarching career goals and evaluate my progress. This proposal represents a novel research line for which I will be responsible and is specifically designed to help me establish an independent investigation, ultimately advancing the field of GBM therapy by supporting my long-term goal of integrating metabolic targeting with precision drug delivery to the brain.


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: 2026 ( Subtotal = $214,101 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/6/2026	NEW	$214,101
														Subtotal = $214,101

Grand Total All Awards = $214,101

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MRI-guided focused ultrasound to enhance ME3BP7 delivery as a novel therapy for Glioblastoma

Award Number: K08NS140637

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 03/06/2026

PERIOD OF PERFORMANCE END DATE: 02/28/2031

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