2022 GRANT Award Details

SEED GRANT

Grantee: Johns Hopkins University
Project Lead: Stavroula Sofou, PHD
Grant Title: Alpha-particle radiotherapy for glioblastoma
Program Area: Glioblastoma Treatment
Grant Type: UKF Seed Grant
Year Awarded: 2022
Amount: $50,000
Duration: 1 year

Summary: Glioblastoma is a type of brain cancer that remains incurable. Our strategy aims to enable uniform delivery of a cytotoxic agent (an alpha-particle emitter) in established glioblastoma tumors with minimum toxicities to the surrounding healthy brain. Our approach is aimed to be more effective in inhibiting brain tumor progression than currently available treatment methods. If successful, this strategy will represent a new paradigm in alpha-particle radiotherapy for glioblastomas, enabled by a nanoparticle platform with an excellent safety profile. The resulting therapeutic intervention will have the potential to extend remission, improve the quality of life and prolong survival of patients diagnosed with glioblastoma who endure surgery, combinations of therapeutics and radiotherapy but who have a poor prognosis with no other options.

SEED GRANT

Grantee: Beckman Research Institute of City of Hope
Project Lead: Qiang Lu PHD
Grant Title: Engineering inhibitors of the ERKS axis proteins for glioblastoma treatment 
Program Area: Glioblastoma Treatment
Grant Type: UKF Seed Grant
Year Awarded: 2022
Amount: $50,000
Duration: 1 year

Summary: Targeting cell fate regulators in brain tumor stem/progenitor cells to develop oligonucleotide-based therapeutics for glioblastoma.  

SEED GRANT

Grantee: University of California Los Angeles
Project Lead: Aparna Bhaduri, PHD
Grant Title: Characterizing PTPRZ1 Mechanism in Cancer as a Therapeutic Target
Grant Type: UKF Seed Grant
Year Awarded: 2022
Amount: $50,000
Duration: 1 year

Summary: Glioblastoma (GBM) is the most common and most aggressive form of adult brain cancer. Unfortunately, most patients succumb to the disease within 12 – 18 months of diagnosis as limited treatment options exist. In our previous work, we identified that a cell type that exists in the developing human brain is reactivated as a cancer stem cell. This population, called “outer radial glia” are highly marked by a gene called PTPRZ1 which sits on the cell surface. Importantly, this outer radial glia are very common in human brains during development but very rare in mice, making them hard to study in mouse or rat models of brain development and GBM. This gene, PTPRZ1, has also been shown by others to be required for GBM progression and spread across the brain. These pieces of data indicate that PTPRZ1 should be a tantalizing drug target, especially because it sits partly on the outside of tumor cells. However, the existing literature on PTRPZ1 is conflicted regarding whether its catalytic activity (its functional pocket) is or is not required for tumor progression. This study seeks to characterize how PTRPZ1 works in GBM, to then design a drug to interfere with its function and limit its ability to promote GBM progression.

SEED GRANT

Grantee: University of California San Francisco
Project Lead: Hui Lin, PHD and Janine Lupo, PHD
Grant Title: Developing Multimodal Deep Learning for Outcome Prediction in Glioblastoma Patients after Radiation Therapy
Grant Type: UKF Seed Grant
Year Awarded: 2022
Amount: $50,000
Duration: 1 year

Summary: In this study we aim to develop a multimodal knowledge fusion platform that incorporates patient-specific representations learned from MRI, radiotherapy treatment plans and clinical features using Artificial Intelligence (AI), MR imaging, and clinical domain knowledge, to empower the outcome prediction of Glioblastoma (GBM) patients. 

RENEWAL GRANT

Grantee: Mayo Clinic
Project Lead: Hugo Guerrero-Cazares
Grant Title: Targeting the malignant interaction between glioblastoma and the subventricular zone
Grant Type: UKF Seed Grant and 2nd YearRenewal
Year Awarded: 2021 and 2022
Amount: $100,000
Duration: 1 year + 1 year renewal

Summary: Glioblastoma Multiforme (GBM) is the most common and aggressive tumor in the brain. Among GBMs, those that are located near an area of the brain called the lateral ventricles (LV) are the ones with the worst prognosis. The reasons for this observation are unknown, we have determined cancer and non-cancercells near the LV interact with each other and induce a more aggressive cancer behavior. Our laboratorynow studies the communication between cancer and non-cancer cells in the brain. We utilize cells derived from GBM patients and cutting-edge molecular tools like cell-specific proteomics, to identify potentialtherapeutic targets that are evaluated in preclinical models. Our goal is to develop new comprehensivestrategies to treat glioblastoma that take into consideration the brain tumor microenvironment. We areconfident this approach will increase our chances of offering GBM patients a better therapeutic prognosis.

COLLABORATION GRANT

Grantee: Columbia University
Project Lead: Osama Al-Dalahmah, MD
Grant Title: Targeting the Microenvironment of Glioblastoma to Block Tumor Progression
Grant Type: Discovery Grant with the American Brain Tumor Association
Year Awarded: 2022
Amount: $50,000
Duration: 1 year

Summary: Glioblastoma (GBM) is a devastating malignant brain tumor that defies surgical resection and traditional therapies. Despite the advances in GBM management, patient survival is dismal because there are no effective therapies. Recent efforts examined targeting cells other than GBM cells, mainly immune cells, as a potential treatment for GBM, but this approach was ineffective. This may be due to the nature of the cells that reside in the periphery of the tumor resected by the neurosurgeon (resection margin), which consists of few tumor cells and immune cells, and many neurons and astrocytes.

Astrocytes are the major support cells in the brain that maintain the health and function of other brain cells. Evidence suggests that astrocytes contribute to GBM spread and growth. My preliminary data suggests molecules that come from astrocytes can promote GBM progression. In this study, I hypothesize that eliminating these molecules, and thereby blocking the interaction between the astrocytes and GBM cells, will lead to reduced GBM spread, increased GBM cell death, and may make GBM more vulnerable to therapy. I will test this hypothesis in animal models of GBM, patient derived GBM tissue, and cellular models of GBM using a combination of cutting-edge molecular studies designed to test GBM cell function and gene expression. My project has the potential to uncover novel therapies for GBM based on targeting astrocytes and may provide neurooncologists with additional tools to combat GBM.

RENEWAL GRANT

Grantee: MD Anderson Cancer Center
Project Lead: Vidya Gopalakrishnan, PHD
Grant Title: Repurposing Migraine Treatments for DIPG
Grant Type: UKF Seed Grant and 3 renewals
Year Awarded: 2019, 2020, 2021, 2022, and 2023
Amount: $250,000
Duration: 5 years

Summary: Diffuse Intrinsic Pontine Glioma (DIPG) is an incurable pediatric brain tumor. It represents nearly 10% of all pediatric central nervous system tumors. Approximately 80% of human DIPGs exhibit a recurrent H3K27M mutation and 75% of these are found in the H3F3A gene, which encodes histone H3.3. The less than two-year survival rate in patients highlights the desperate need for treatments. 

With the support of the Uncle Kory Foundation, Dr. Gopalakrishnan and her team at The University of Texas MD Anderson Cancer Center in Houston, Texas, have discovered that a protein called REST is expressed at higher levels in DIPG tumors than in normal tissue and is required for DIPG growth. A REST-context specific chemical screen using re-purposable drugs identified candidates that target cell-surface receptors controlling cell-cell communication in the nervous system as having potential for therapeutic evaluation. Pre-clinical studies with cell culture and mouse orthotopic models of DIPG confirmed that DIPG cells harboring the H3K27M mutation were indeed more sensitive to these drugs than DIPG tumors expressing wildtype histones and that REST elevation further increased their drug sensitivity. Future studies will be two-pronged. The first will be directed at clinical translation of the above findings through Phase I/II studies. The fact that these agents are already used in children to treat neurological disorders will facilitate our application to the FDA requesting their study in patients with DIPG. The second will involve multi-omics studies to understand the molecular characteristics of tumor cells that respond and those that don’t. This will allow us to develop combination treatments to target the non-responders.

The Gopalakrishnan group are very grateful to the Uncle Kory Foundation and their team for their support in getting a high-risk project off the ground!