Maria Castro, Ph.D. Grant Support

Systemic Delivery of Targeted Bi-Compartmental Nanoparticles for Glioblastoma Therapeutics 

Castro M, Lahann
NIH R01 NS124178-01A1         

Major Goals: Glioblastoma multiforme (GBM) is a malignant primary brain cancer which carries a dismal prognosis. STAT3 has been shown to be a very attractive therapeutic target for GBM; albeit small molecule inhibitors of STAT3 signaling are ineffective, as they exhibit very poor blood brain barrier permeability. Our interdisciplinary team will develop and evaluate a novel and scalable bi-compartmental nanoparticle delivery system that allows controlled co-released of STAT3 siRNA and the chemotherapeutic agent, paclitaxel. This work may result in a new treatment modality for GBM, a tumor type, for which no effective treatments exist. 

Principal Investigator 

Uncover the role of H3.3-G343R mutation in shaping the DNA damage response, anti-tumor immunity and mechanisms of resistance in glioma. 

Castro M, Lowenstein P
NIH 1R01NS122165-01A1

Major Goals: We propose to test the hypothesis that H3.3G34R reshapes the epigenetic landscape, resulting in alterations in chromatin states and transcriptional changes. These alterations cause DDR impairment and induce genomic instability which in turn leads to cGAS-STING-Pathway-mediated activation of the immune system with the H3.3G34R pHGG TME. 

Principal Investigator

Non-invasive Transcranial Histotripsy Treatment in a Murine Primary Malignant Brain Tumor Model

Castro M, Pandey A, Xu

Major Goals: Approximately 256,000 new patients are diagnosed with primary brain tumor annually worldwide, and many more patients have brain metastases. The goal of this proposal is to investigate whether transcranial histotripsy, a proposed novel and non-invasive treatment of brain tumors, can lead to survival benefit in a murine primary malignant brain tumor model.


The role of collagen and its signaling mechanisms in glioma progression and invasion 

Castro M, Lowenstein P
NIH R01 NS122234-01A1
09/01/2021 –08/31/2026 

Major Goals: Gliomas are incurable tumors. We recently discovered that Collagen 1A1 is expressed at high levels in perivascular cells and also in tumor cells themselves. We will now examine the role of Collagen 1A1 in each cell type. To do so we will explore whether cell-type specific depletion of Collagen 1A1 from glioma cells will halt tumor progression. These results will permit to develop therapeutics targeted to collagen expression. 

Co-Principal Investigator

Chem-immunotherapy strategy for pediatric high grade glioma

Castro M, Schwendeman S
NIH R21 NS123879-01

Major goal: Develop HDL NP for the treatment pf pediatric high grade gliomas harboring H3G34R mutations 

Principal Investigator

Novel nano-vaccine technology for inducing immunity against gliomas 

Castro M, Moon J
NIH RO1 NS122536

Major Goals: The proposed research is relevant to public health because these studies will improve our understanding of the biology-materials interfaces and may lead to new design principles for biomaterials engineered to elicit robust levels of immune responses, thereby addressing current technical limitations in vaccine technologies. 

Principal Investigator

Artificial Intelligence platform for early detection of brain metastatic risk at diagnosis

Merajver, Castro M
NIH/NCI R21CA245597
03/01/2020 - 02/29/2022

Major Goal: BBB-niche on a chip for determination of breast cancer cells’ metastatic potential to the brain.


Immune-suppressive myeloid cells in the glioma microenvironment: Signaling mechanisms and novel therapeutic strategies

Castro M, Lowenstein P, Muraszko K
NIH R37-NS094804-01 (R01-NS094804)
9/1/2015 – 6/30/2022

Major goal: To elucidate the role played by CXCR4-CXCL12 signaling in the GBM microenvironment in mediating the accumulation of IMCs, facilitating tumor invasion and disease progression. We hypothesize that CXCR4 blockade will enhance the efficacy of anti-GBM immunotherapies and will uncover a novel therapeutic target for this devastating cancer. 

Principal Investigator/Javits Award Recipient 

Interactions between the tumor cells and the neuro-immune microenvironment in mutant IDH1 gliomas: implications for therapeutics

Castro M, Ljungman M, Lowenstein P, Sartor M, Venneti S, Zhao L
NIH/NINDS R01-NS10555603S1
5/1/2018 – 4/30/2023

Major goal: To study a subtype of gliomas which harbor mutations in the ATRX gene (mATRX), p53 mutations, and mutation in the enzyme, isocitrate dehydrogenase 1 (mIDH1). Our goal is to assess the molecular mechanisms by which mATRX and mIDH1 impact the biology of the tumors and influence the tumor immune microenvironment. We will also determine the response to immunotherapies.

Principal Investigator  

Cancer Biology Training Program

Castro M, Lombard D
NIH T32-CA009676
9/1/2018 – 8/31/2023

Major goal:  An interdisciplinary program whose central goal is to train exceptional junior investigators to address fundamental biological problems related to human cancer. The Program trains both predoctoral and postdoctoral scholars with research opportunities focusing on a wide choice of topics in the field of cancer biology.

Principal Investigador  

Immune-mediated therapies in a genetically engineered murine model of diffuse intrinsic pontine glioma

Castro M, Lowenstein P
NIH R21NS107894-01
4/1/2019 – 3/31/2022

Major goal:  Identifying novel immunotherapeutic strategies in a mouse DIPG model.

Principal Investigator  

Tuning biomaterials-immune cell interactions for treatment of glioblastoma multiforme

Castro M, Lowenstein P, Moon J
NIH R01-EB022563
9/7/2016 – 5/31/2020

Major goal: Despite recent advances in surgery, chemo-and radiation-therapy, patients with glioblastoma multiforme (GBM) have a grim prognosis.  In this application, we propose to exploit our nanoparticle-based vaccine technology to achieve strong cellular and humoral immune responses against GBM.  Overall, the work proposed will address current technical limitations in cancer vaccines and potentially lead to a new treatment option for patients suffering from brain cancer.

Principal Investigator  

Tumor targeting of Nanoparticles as therapeutic siRNA carriers for pediatric high grade gliomas (pHGG)

Castro M, Lowenstein P
Ian's Friends Foundation
5/1/2021 – 4/30/2022

Major goal: Our laboratories focus is to develop novel therapeutic strategies to improve patient outcomes with malignant brain tumors.

Principal Investigator  

Understanding the tumor microenvironment and immune system in brain tumors

Castro M
Rogel Faculty Scholar Program, Rogel Cancer Center
6/1/2019 – 45/30/2024

Major goal:  To elucidate the molecular and cellular landscape within the tumor microenvironment of low grade gliomas. Identification of novel therapeutic targets.

Principal Investigator  

Immunotherapeutic approach for DIPG; pre-clinical testing

Castro M, Lowenstein P
Chad Tough Foundation and Sophie's Smile
7/1/2019 – 6/30/2029 

Novel combined immunotherapeutic strategies for glioma: Using pet dogs with spontaneous high-grade glioma

Castro M, Lowenstein P, Pluhar E
NIH/NCI 1U01CA224160-01 (On subcontract with University of Minnesota)
9/01/2017 – 8/31/2022

Major goal:  Develop and implement a phase I clinical trial for novel immunotherapies in dogs bearing GBM.

Co-Principal Investigator 

Novel Immune Mediated-Gene Therapy for Pediatric High-Grade Glioma

Castro M, Lowenstein P
Pediatric Brain Tumor Foundation (NYC) and the Samson Research Fund
7/1/2019 – 6/30/2023

Major Goal: Implement a novel gene thrapy mediated immune-therapeutic approach in preclinical models of pediatric high grade gliomas (pHGG)

Michigan Medicine Headline article about this project.

Principal Investigator 

Blocking STAT3 signaling via systemic delivery of targeted nanoparticles for glioblastma therapy

Castro M
Forbes Institute Cancer Center Award
9/1/2020 – 8/31/2022

Major goal:  Assess the therapeutic efficacy and safety of tumor targeted nanoparticles encapsulating STAT3i in preclinical models of high grade gliomas. Implementation of novel therapeutic targets.

Principal Investigator 

Brain Cancer: Novel Technologies, preclinical testing and clinical implementation 

Castro M, Schwendeman S
Biosciences Initiative – Scientific Initiative Program
9/01/2020 – 8/31/2026

Major goalsDespite recent advances in surgery, chemo-and radiation-therapy, patients with high grade gliomas (GBM) face a dismal prognosis.  We propose to exploit our nanoparticle-based technologies to achieve strong cellular and humoral immune responses against GBM.  Additionally, we will also develop novel delivery platforms for chemotherapies and immune-mediated gene therapies for GBM. Overall, the work proposed will address current technical limitations in cancer vaccines and potentially lead to a new treatment option for patients suffering from malignant brain cancer.

Principal Investigator

Principal Investigator

Maria G. Castro, Ph.D.

R. C. Schneider Collegiate Professor of Neurosurgery
Professor, Cell and Developmental Biology
Director, NIH Cancer Biology Training Grant
Steering Committee Member, Woman of Color in the Academy Project (WOCAP)