Research
Improving delivery of therapies for malignant brain tumors
Malignant brain tumors such as glioblastoma (GBM) remain among the most aggressive and difficult cancers to treat, in large part because many therapies cannot effectively reach the tumor due to the blood-brain and blood-tumor barriers. Our research addresses this delivery problem directly: rather than working around the vasculature, we work through it. Using a novel approach called endovascular selective intra-arterial (ESIA) infusion, therapeutic agents can be delivered through microcatheters navigated into distal intracranial blood vessels that directly feed the tumor, allowing more targeted and potentially more effective treatment.
Endovascular delivery of cellular therapeutics (MSC-D24)
In collaboration with the Lang Laboratory, we are evaluating intra-arterial delivery of mesenchymal stem cells loaded with the tumor-selective oncolytic adenovirus Delta-24-RGD (MSC-D24) for GBM in a Phase 1 clinical trial (NCT03896568). These engineered cells home to tumor tissue and release virus that selectively kills GBM cells while triggering a broader anti-tumor immune response. Compared with direct intratumoral injections, endovascular delivery is less invasive, can be repeated more readily, avoids backflow along the injection tract, and may provide broader distribution of therapeutic agents throughout the tumor bed by using the tumor’s own vascular supply. Building on this approach, our team is evaluating whether ESIA can be combined with methods that temporarily open the blood-brain barrier to further improve delivery. This work aims to establish a flexible transvascular platform for delivering a range of brain tumor therapies and to accelerate the clinical development of safer, more effective treatments for patients with GBM.
Comparing methods of BBB disruption to enhance endovascular delivery
A core focus of our preclinical program is systematically comparing methods for transiently opening the blood-brain barrier (BBB) and blood-tumor barrier (BTB) to potentiate delivery of therapeutics given via ESIA. Using orthotopic glioma models, we have evaluated intra-arterial mannitol (osmotic), an oral phosphodiesterase-5 (PDE-5) inhibitor (pharmacologic) and stereotactic focused ultrasound (mechanical) — comparing each method's safety, degree and duration of barrier opening and tumor selectivity. We are now building on these findings to characterize how each disruption method — alone and in combination with endovascular therapeutics — shapes the anti-tumoral effect and the tumor immune microenvironment.
Image-guided precision endovascular delivery
Our lab is developing next-generation imaging and machine learning tools to make endovascular delivery more accurate and reproducible. By combining real-time microcatheter perfusion imaging with AI-based vascular segmentation, we identify the arterial pedicles feeding a tumor and guide multi-pedicle, super-selective infusion — moving beyond single-pedicle delivery to treat several distal branches in one procedure. Catheter position is only part of the equation. How much therapeutic actually reaches the tumor also depends on local blood flow dynamics, the agent's physical properties (size, molecular weight, formulation) and the degree of BBB/BTB disruption achieved. We are exploring computational fluid dynamics (CFD) modeling to study how these factors interact, building a mechanistic framework for optimizing endovascular drug delivery to brain tumors.
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Research Areas
Find out about the four types of research taking place at UT MD Anderson.