Research Funding & Impact

ABTA-Funded Research Projects

2021 Research Funding 

Guided by our mission, and advised by a multidisciplinary team of experts, the ABTA is dedicated to funding research that has the potential to change the lives of people affected by brain tumors. We also aim to “seed the field” with promising up-and-coming researchers in the brain tumor space.

  • The ABTA awarded $427,000 in grants to 17 new projects
    • $400,000 funded 8 Discovery Grants
    • $27,000 funded 9 Medical Student Summer Fellowships
  • The 2021 funded projects span multiple tumor types:
    • Glioblastoma
    • Malignant Glioma
    • Primary CNS Lymphoma
    • Ependyoma
    • Brain Stem Glioma
    • Medulloblastoma
  • Research areas of focus:
    • Drug Therapies/Experimental Therapeutics
    • Immunology/Immunotherapy
    • Gene Expression/Transcription/Epigenetics
    • Viral Therapy
    • Biomarkers

2021 Newly Awarded Grants

Discovery Grant Grant

A Discovery Grant is a one-year, $50,000 grant to support cutting-edge, innovative approaches that have the potential to change current diagnostic or treatment standards of care for either adult or pediatric brain tumors.

Wajd Al-Holou, MD

Institution: The University of Michigan

Mentor: Maria Castro, PhD 

Tribute: In honor of Joel A. Gingras, Jr.

Glioblastoma (GBM) is the most lethal brain tumor with an average survival of around 15 months. This cancer forms from abnormal mutated brain cells that grow out of control and expand through the brain. Despite aggressive treatment, essentially all tumors recur. All previous therapies tested have failed to treat GBM due to the significant differences, or heterogeneity, of the tumor cells. Thus, not only are GBM tumors/cells different between individual patients, but also within an individual tumor each region contains unique cells with unique mutations. To make things even more complicated, research has shown that at the microscopic level, interactions between cancer cells and the normal cells nearby (for example blood vessels, immune and brain cells) protect the cancer cells from treatments. This allows GBMs to easily adapt to therapies and continue growing. We have failed to identify new treatments because we have failed to understand the incredible heterogeneity of GBMs.   

Using state-of-the-art genetic technology, we can define cancer cell vulnerabilities by defining their location in relation to nearby cells and their genetic makeup. Our in-depth analysis will allow us to identify ways to target these vulnerabilities to identify new therapies to treat this devastating tumor and follow-up laboratory studies will identify if these therapies have significant impact. 

Terrance Burns, MD, PhD

Institution: Mayo Clinic in Rochester, MN

Mentor: Jann N. Sarkaria, MD

Tribute: Supported by Southeastern Brain Tumor Foundation 

IDH-mutant gliomas are the most common gliomas of young adults. Despite initial sensitivity to chemotherapy and radiation, they invariably progress into treatment-resistant and ultimately fatal tumors. Translation of novel therapies for glioma is complicated by the lack of biomarkers that indicate treatment effectiveness.  

Survival remains the gold standard outcome measure. Clinical trials for patients with IDH-mutant gliomas may require a decade to yield survival results, hampering timely progress in a complex field. When trials fail, as is typically the case, few insights into why the treatment failed are available to guide therapeutic improvements. The cycle is then repeated with new novel candidates leading to a growing list of failed drugs without clear directions for improvement. New tools are urgently needed to accelerate discovery of novel therapies.  

Here we propose to evaluate biomarkers from live human IDH-mutant gliomas during surgery, and will compare these to findings from mice carrying human IDH-mutant gliomas. We will also determine if biomarker levels from the live tumor respond to currently available therapies in real time in mice. If so, this work can provide a path forward to more rapidly determine which therapies or combinations are most effective within individual patients.  We are optimistic that this strategy can open a new frontier of rapid individualized feedback which is so urgently needed to cure gliomas. 

Paul Castillo, MD

Institution: University of Florida

Mentor:  Duane Mitchell, MD, PhD

Tribute: Supported by An Anonymous Family Foundation

Lymphomas of the brain are tumors that arise from white blood cells, the infection fighting cells, called B cells, located in the brain. The malignant B cells do not travel to organs outside the central nervous system and thus, they are called primary central nervous system lymphomas. Most of patients who initially present with brain lymphomas get cured but just temporarily. Up to 6 out of 10 patients with this disease will have their lymphoma back months down the road and at this point, this type of cancer is almost never curable with currently available therapies.  

Training the immune system via immunotherapy to become soldiers to combat B cell blood cancer (i.e., leukemias and lymphomas) has shown great promise to induce sustainable and high cure rates. However, the current immunotherapies attack B cell cancers that have external markers also shared by normal B cells, thus killing the normal B cells as well. Furthermore, a good number of those patients, even after being “cured” with a given immunotherapy, have their disease back after some time as their tumors learn to escape from their destruction. In this study, we propose a novel strategy to destroy B cell cancer cells while leaving normal B cells by educating the immune system to distinguish between cancer cells and healthy cells. This approach will also target multiple markers as opposed to one or two markers, reducing the chances of escaping to the attack from the immune system and hence, lower chances for the cancer to come back. 

Florence Cavalli, PhD

Institution: Curie Institute

Mentor: Olivier Ayrault, PhD

Tribute: Supported by Humor to Fight the Tumor

Cancer cells arise from deregulation of normal cells. Tumors hijack the gene regulation machinery that is responsible for normal development in order to drive tumor development and recurrence. Many studies have focused on identifying tumor-specific genetic events (e.g. mutations) but much less is known regarding the key regulators of gene expression driving the cancer state. I aim to identify and study those key regulators in two major understudied areas: tumor temporal heterogeneity (or differences observed between primary and recurrent tumors), and tumor spatial heterogeneity (or differences observed between the population of cells within a tumor).


These types of heterogeneity are of critical importance since they represent major causes of treatment failure. I will analyze primary-recurrent pair samples of oligodendroglioma tumors, an understudied but a common adult high-grade brain tumor type. Most of these tumors recur and are ultimately fatal. It is therefore critical to further study them. I will study the tumors at a single-cell resolution to identify and compare the key regulators of the cell populations within the tumors. The information from this comparison will reveal the cell of origin of the recurrence from the primary tumors and the common recurrent specific key regulators. I will then propose drug targets to kill the cells that initiate tumor recurrence, to attack them early, before recurrence can begin. This project will provide important novel biological insights which can lead to new therapeutic strategies and to the development of models to study the disease.

Jian Hu, PhD

Institution: University of Texas M.D. Anderson Cancer Center

Tribute: In honor of Joel A. Gingras, Jr.

Glioblastoma (GBM) is the most frequent and deadliest primary brain tumor. With the advent of immunotherapy, a number of cancers previously unresponsive to all types of therapies have been successfully treated and even cured. Unfortunately, immunotherapy in its current form has not been shown to exert a clinical benefit for most GBM patients, probably due to unique composition and features of immune cells found in GBM. Due to certain defects in these immune cells, they have turned themselves from attackers of cancer cells to helpers of cancer cells. 

Our previous work has identified a class of important molecular regulators for these immune cells in GBM that could be used for GBM therapy. We have found that two potent and safe drugs that were developed for other diseases could effectively fix the immune cells in GBM and make them able to recognize and attack cancer cells again. Our proposal will help us further understand how these drugs achieve their functions of fixing immune cells and develop better therapeutic approaches by combining with other types of immunotherapies. 

Markus Siegelin, MD

Institution: Columbia University

Tribute: Supported by the Sontag Foundation

Glioblastoma (GBM) is the most common primary malignant brain tumor with poor prognosis and essentially no durable treatment. Tumor growth is ultimately determined by nutrients/energy. Tumor tissues have developed unique strategies to enable their growth and to secure their survival under conditions of nutrient absence. Originally considered as a waste product of breaking down sugar for energy and probably better known from exercise physiology, lactic acid accumulates to a significant amount in the infiltrative edge of GBM tumors.  

We have made the intriguing observation that in clinically relevant model systems of glioblastoma, lactic acid is heavily utilized for energy in cell culture and more importantly in mouse models. Moreover, lactic acid is critical for glioblastoma cell survival when sugar levels are low. In order to mediate this survival benefit, lactic acid regulates the so called epigenome, which in part is comprised of chemical modifications on the DNA and proteins that ultimately regulate gene expression. Interference with lactic acid mediated regulation of the epigenome using a clinically validated drug, CPI-613 extends animal survival in mice. Following completion of the study our research will establish lactic acid metabolism as a therapeutic target in glioblastoma. 

Eric Thompson, MD

Institution: Duke University

Tribute: Supported by An Anonymous Family Foundation

Current adjuvant therapy for the malignant brain tumors medulloblastoma and pediatric high grade glioma (HGG) is marginally effective and often toxic. A promising alternative to current radiochemotherapy is oncolytic viral therapy (OV) which is currently being explored in clinical trials. However, the mechanism of tumor cell death from these OVs are currently unclear. Furthermore, it is unclear why some patients have durable long-term overall survival with OV, while many experience no real benefit. 
We have recently discovered that oncolytic viruses cause profound oxidative stress on tumor cells, resulting in cell death. Furthermore, we have found that tumor cells with high levels of anti-oxidants are resistant to OV. Given that one key process by which OV kills cancer cells is the induction of profound oxidative stress, we hypothesize that medulloblastoma and HGG resistance to OV is mediated by the cancer cells’ strong anti-oxidant capacity.  
The aim of this project is to determine the specific molecular pathways of oxidative stress of brain tumors that confer resistance to OV. This study will identify genes that change in response to OV in medulloblastoma and pediatric HGG. We hope to identify therapeutics to overcome resistance to OV, resulting in better outcomes for more patients. 

Lee Wong, PhD

Institution: Monash University

Tribute: Supported by An Anonymous Family Foundation

Paediatric gliomas are fatal, and are the leading cause of cancer-related mortality in children. The median survival ranges from 12 to 60 months with a 5-year survival of less than 20%. Treatment for paediatric glioma remains an unfulfilled need in clinical neurooncology. Recent DNA sequencing studies have shown that paediatric gliomas often have mutations in histone proteins which help fold and package DNA. Histones are also described as suitcases that sort our DNA to regulate gene activities. In paediatric glioma, histone mutations result in the failures of cells to turn on the right genes and establish the correct identity, therefore, trapping them in a stem cell-like tumour state that divide uncontrollably. 

This exciting discovery brings new hope for developing effective therapies for paediatric gliomas. To translate this new knowledge into clinical patient management and patient outcomes, this study will utilise sophisticated DNA and protein technologies to investigate how histone mutations change DNA packaging and trap the cancer in an immortal stem-cell like behavior to drive cancer formation. This study will also identify factors that can restore the normal cell behavior and development to paediatric gliomas. The knowledge gained from this study will identify effective and specific therapeutic targets for paediatric gliomas. 

Gelareh Zadeh, MD, PhD, FRCSC, FAANS

Institution: University Health Network

Tribute: Supported by An Anonymous Family Foundation

Currently, diagnosing glioma tumors requires surgery, which is associated with significant anxiety and in some cases may cause complications leading to significant complications and even death. In addition, determining whether a glioma has recurred or is responding to treatment requires imaging, which is not always reliable.  

Tumors shed cancer cell DNA into the bloodstream (also called circulating cell-free tumor DNA or cfDNA). Obtaining a sample of cfDNA from blood provides an opportunity to non-invasively ‘biopsy’ tumors to establish a diagnosis for patients’ tumors and avoid unnecessary surgery. We have recently shown in working with our collaborator, Dr. Daniel De Carvalho, that certain changes in cfDNA (so-called DNA methylation) can help diagnose brain tumors. This work was published last year in the journal Nature Medicine.  

In this project, we will assess the utility of cfDNA methylation profiling for noninvasive detection of glioma recurrence after treatment and monitoring the tumor’s response to chemotherapy and radiation throughout the course of the treatment. This application of our technology could transform clinical management of glioma patients and reduce the need for high-risk surgical procedures altogether. 

Jack & Fay Netchin Medical Student Summer Fellowship

A Medical Student Summer Fellowship is a three month, mentor-guided summer research experience, intended to motivate talented medical students to pursue a career in neuro-oncology research.


Kaitlin Stitz

Institution: The Hospital for Sick Children 

Mentor: Vijay Ramaswamy, MD, PhD 

Tribute: In memory of Amy Krisburg


The most common malignant brain tumor of childhood is medulloblastoma (MB), and it represents one of the biggest challenges in pediatric neuro-oncology. Current treatments are limited to aggressive surgeries, radiation, and chemotherapy; however, certain subtypes of MB remain highly resistant to therapy. Specifically, a subgroup of MB, the SHH subgroup almost uniformly fail current therapy, likely due to radioresistance, and are deemed very high-risk MB. As such, new treatment approaches for this group are urgently needed. Our proposed project aimed to identify drugs which make SHH MB cancer cells more sensitive to radiotherapy by using the cancer cell’s own response against it. This summer, I was able to characterize and establish new models of radiation resistant SHH MB cells, which recapitulate the radiation resistance we observe in children. I then performed a screen of drugs called epigenetic modifiers, which are already available for clinical use and alter how DNA is read. This screen identified two novel classes of drugs that have not been previously used in MB which significantly enhance the effect of radiation. We are currently investigating this novel treatment avenue further as it has the potential to be translated to the clinic for this incurable subgroup of MB. 

Jessica Chen, PhD

Institution: University of California, Los Angeles

Mentor: Stephanie Seidlits, PhD 

Tribute: In memory of Rose DiGangi

Glioblastoma is one of the most prevalent and deadliest brain cancers, despite aggressive surgical resection, radiation therapy, and chemotherapy. To understand how tumor cells spread and become treatment resistant, and to develop new therapies that target these cells, the tumor cells need to be removed from the patient and grown in the laboratory for experimental studies. However, when transferred to standard cell culture conditions, many of the cells that may be responsible for glioblastoma spread and treatment resistance will die, such that drugs that work in the laboratory do not end up working in the patient. Therefore, our goal is to engineer a laboratory microenvironment, consisting of molecules found in abundance in normal brain tissues, so that the new home looks similar in composition to the tumor cell’s original home in the human body. This way, more cells will survive and behave similarly to how they did before the relocation, thus allowing for more accurate drug testing studies. In a matter of a couple of days, we can grow many sets of cells from a single patient tumor, enabling us to test many different drugs, very quickly, and all at once, eventually allowing physicians to be better informed when developing personalized treatment plans. For a cancer as aggressive and lethal as glioblastoma, a fast and reliable means of drug testing has the potential to yield significant improvements in patient outcomes.

Nicholas Cho, BS

Institution: University of California, Los Angeles

Mentor: Benjamin Ellingson, PhD

Tribute: Supported by BrainUp

Currently, there is no standard of care for IDH mutant gliomas, but there are clinical trials of IDH-inhibitors with hopes of providing targeted therapy. As a result, there is a clinical need to discover non-invasive imaging biomarkers that can characterize IDH-inhibitor treatment response. However, one challenge is that a tumor’s metabolic environment is diverse, so a novel imaging biomarker that combines information from multiple magnetic resonance imaging (MRI) techniques may provide more insights into tumor characteristics and treatment changes than a single MRI technique alone.

My project aimed 1) to explore a novel, non-invasive, and multi-modal imaging biomarker for brain tumor metabolism called Aerobic Glycolytic Imaging (AGI) and 2) to characterize the treatment response of IDH-inhibitors in IDH mutant gliomas using multiple MRI techniques. AGI is a biomarker that combines perfusion MRI data with our lab’s novel acidity- and oxygen-sensitive MRI technique. In one study, we biologically validated AGI in patients as a measure of tumor metabolism and determined that AGI can successfully differentiate various tumor types, grades, and regions based on their metabolic characteristics. We then explored MRI changes following IDH-inhibitor treatment and observed that there is increased blood vessel volume and increased AGI in IDH mutant gliomas. Future work will involve continuing to characterize IDH-inhibitor treatment response using single- and multi-modal MRI metrics.


Mihai Dumbrava, BMSc

Institution: Mayo Clinic in Rochester, Minnesota 

Mentor: Jann N Sarkaria, MD 

Tribute: Supported by the Uncle Kory Foundation 

Glioblastoma (GBM) is the most common and deadly adult brain cancer with an average survival rate of 14 months following diagnosis. GBM has a dire prognosis despite aggressive surgical resection, radiation, and chemotherapy, and there is a need to develop novel and curative treatments. Unfortunately, patients with GBM tumors suffer due to inherent or acquired resistance to the current FDA-approved treatments including temozolomide and lomustine (CCNU). Several key molecular indicators, including O6-methylguanine methyltransferase (MGMT) activity and DNA mismatch repair (MMR) status, are linked to the variable response of GBM tumor patients to therapy.

VAL-083 is a promising  chemotherapeutic that works differently from temozolomide and CCNU and may be able to overcome resistance in GBM tumors. The mechanisms of sensitivity and resistance to VAL-083 in GBM are largely unknown; therefore, we aimed to understand what factors in tumors might contribute to sensitivity or resistance to this new drug.

We found that sensitivity to VAL-083 therapy does not depend on MGMT or MMR status, known to confer resistance to standard of care treatment in GBM patients. We also show that members of the DNA-damage response may be activated following VAL-083 therapy. Further studies are needed to understand how the activation of these pathways will impact sensitivity to Val-083. Identifying a molecular signature sensitive to VAL-083 therapy alone and in combination with other agents will help to know which patients are likely to have good outcomes from VAL-083 treatment.


Michael Meadow, BS

Institution: University of Rochester 

Mentor: Nimish Mohile, MD

Tribute: Supported by the Uncle Kory Foundation

This project set out to understand the mechanisms by which the levels of the protein Sirtuin 6 (SIRT6) are reduced in glioblastoma. Furthermore, we sought to target this down regulation in hopes of developing a novel therapeutic. We found that, contrary to the limited existing literature, SIRT6 is not down regulated in glioblastoma cell lines relative to normal astrocytes. Additionally, we discovered that SIRT6 is distinctly modified in all three glioblastoma cell lines tested in this project. The exact identity and consequences of this modification remain unclear at present, but these results represent an exciting and novel line of experimentation moving forward. We hope to continue to characterize the basic biology of these modifications and identify these modifications in patient derived glioblastoma samples. Overall, the project has opened up a new avenue for glioblastoma research that could lead to a better understanding of the cancer and the development of novel therapies.

Yusuf Mehkri, BS

Institution: University of Florida 

Mentor: Maryam Rahman, MD

Tribute: Supported by Southeastern Brain Tumor Foundation 

Traditional cancer vaccines are difficult to produce and are invasive for patients. Our novel hydrogel-based vaccine can function as an off-the-shelf vaccine, has been shown to induce a strong immune response and tumor regression in mouse cancer models, and therefore, is more practical for patients. The goal of my project was to see how this novel vaccine interacts with standard therapy (chemotherapy and radiation) for brain tumors. Based on the immunomodulatory properties of both chemotherapy and radiation therapy, we expected mice with implanted brain tumors who were initially treated with either chemo or radiation and then later with our vaccine would survive the longest. We were surprised to find that mice receiving the vaccine alone survived the longest when compared to different combinations of vaccine and chemotherapy treatments. The results of my immune response study to follow my completed survival study are pending and will allow us to better understand what is going on in the immune cells at the tumor site.


Rohan Rao, BS

Institution: University of Cincinnati 

Mentor: Soma Sengupta, MD, PhD 

Tribute: Supported by the Uncle Kory Foundation 

Glioblastoma (GBM) is the most common primary brain tumor in adults with a mean survival time of 12-15 months. The common treatment paradigm for GBM is gross total resection of the GBM, followed by chemoradiation and chemotherapy. The poor prognosis, despite available treatments, arises from the significant challenges of treating GBM tumors, including: (1) the physical barriers to drugs being delivered to the brain and tumor cells and (2) the highly heterogeneous nature of the cells that form GBM tumors, which leads to recurrence of GBM even when treated by standard-of-care.

We are investigating the use of an advanced technology that is capable of temporarily and non-invasively opening the blood-brain and blood-tumor barriers while administering small, non-toxic nanoparticles carrying an RNA-based therapy designed to shut off key molecules that contribute to GBM cancer cell proliferation and growth.

We are particularly interested in an RNA molecule, miR-26a, which has been shown to be increased in human GBM samples. miR-26a is thought to minimize the activity of a tumor suppressor, PTEN, allowing for tumor progression. We have preliminarily shown that inhibition of miR-26a restores PTEN levels in human-derived GBM cell lines. We now plan on loading a miRNA-26a inhibitor onto lipid nanoparticles manufactured at the University of Cincinnati for more effective delivery to tumor cells.


Paul Rowley, BS

Institution: University of California, San Francisco

Mentor: Janine Lupo, PhD 

Tribute: In honor of Paul Fabbri

Our study will produce a model for risk-adapted radiation therapy based on individualized tumor features identified on several types of advanced MRI. More accurate radiation plan design will both increase radiation dose to potential sites of recurrence and decrease the dose to low risk normal brain tissue, potentially improving disease control and reducing toxicity. Our study will also produce a clinically feasible method for radiation planning with the ultimate goal of producing risk-adapted radiation therapy plans. 

Our work so far has revealed that even with MRI data acquired from different glioblastoma patients on different scanners, it is possible to reliably and quickly generate maps based on white matter surrounding brain tumors that can be used to help outline where optimally to deliver radiation therapy. Additional work is needed, but our preliminary results suggest that our methods could be widely and rapidly implemented in most clinical settings, allowing for improved radiation therapy with fewer toxicities for patients.


Jovanna Tracz, BS

Institution: Eastern Virginia Medical School 

Mentor: Alberto Musto, MD, PhD 

Tribute: In memory of George Surgent

Glioblastoma Multiforme (GBM) is recognized as the most aggressive known cancer of the central nervous system in both children and adults. While the different classes of GBM are diverse, there is evidence that each major class expresses genes that permit glioma cells to form connections with neurons (the cells in the brain that send and receive signals for carrying out brain function). These neuron-glioma connections not only cause hyperactivity in the neurons and in adjacent brain areas (causing symptoms such as seizures), but also allow for glioma cells to further integrate into functional neural circuits and create more tumor cells. How these glioma-neuron connections are established remains unknown.

Our hypothesis states that the molecular signals that form connections between glioma cells and neurons result from the abnormal activation of specific proteins that induce signaling in both tumor cells and nearby functional neurons. As a result, the brain tissue surrounding the tumor expresses neuroinflammatory molecules, such as CD-40, that further promote tumor growth. We use a mouse model, immunohistochemistry, and electrochemistry to study this mechanism by which diseased glioma cells ‘reach out’ to healthy neurons to form cell-to-cell connections. These findings will help to identify molecular markers that can be visualized during neurosurgery and targeted with medical treatment.

2019 & 2020 Ongoing and Recently Completed Projects

Discovery Grant

A Discovery Grant is a one-year, $50,000 grant to support cutting-edge, innovative approaches that have the potential to change current diagnostic or treatment standards of care for either adult or pediatric brain tumors.


Munjal Acharya, PhD

Institution: The University of California, Irvine

Tribute: Supported by Southeastern Brain Tumor Foundation

Radiation therapy (RT) for brain cancers leads to cognitive deficits that badly impact the quality of life. This is a particularly serious problem for childhood cancer survivors who have a normal lifespan but experience reductions in 3 IQ points per year. Unfortunately, few if any effective treatments exist for RT-related cognitive deficits. Our study will provide novel insights into the mechanisms by which RT impacts brain function. Using a mouse model, we will determine how RT disrupts the brain’s inflammatory communication by a series of unfortunate molecular events. We found that RT activates signaling proteins of the complement system, which is part of the immune system that enhances antibody and other immune cells to clear cell waste and pathogens and to promote inflammation. In the brain, it plays important roles in maintaining the memory units called synapses that form memory.

RT leads to uncontrolled activation of complement proteins that eventually leads to inflammation and, may help to spread cancer. Our studies, using an experimental drug (PMX205) to specifically target a component of complement, found that disruption of complement signaling is neuro-protective against radiation injury. This drug is currently under clinical trials in Australia for motor neuron diseases, can be taken orally and showed a minimal toxicity and a very good safety profile. This proposal will determine if combined treatment with radiation and PMX205 will provide an efficient solution to kill cancer as well as preserve normal brain function. Thus, our project will lay the foundation for a novel therapy designed to thwart cancer without damaging the brain function.


Bikash Debnath, PhD

Institution: University of Michigan

Mentor: Alnawaz Rehemtulla, PhD

Tribute: In memory of Mark McLaughlin and in honor of all of those who have given on GBM Awareness Day

Glioblastoma (GBM) is the most aggressive cancer of the brain with the average time of survival being approximately 12 months. Nearly 13,000 new cases of GBM are expected to be diagnosed in 2021 with the expectancy to live 5 years being only 5.9%. Currently, there is no curative treatment option for GBM. 

DNA damage therapies such as radiation and temozolomide initially cause accumulation of DNA double-strand breaks (DSBs) as a part of their tumor cell killing mechanisms. The DNA repair protein, RAD51 plays a major role in the repair of DSBs and contributes to the resistance in GBM stem cells (GSCs). Our bioinformatics analyses discovered a significant association between RAD51 and poor overall survival of GBM patients. 

We have recently identified compounds that bind RAD51 using super computer-based machine learning models. Our laboratory experiments confirm that the compounds are effective at sensitizing GBM cells to radiation as well as temozolomide. 

Given the fact that RAD51 is associated with radio- and chemo-resistance as well as a poor overall survival and disease progression of GBM patients, we hypothesize that inhibition of RAD51 using small molecule inhibitors will sensitize GSCs to radiation and chemotherapy and improve overall survival of GBM patients. 

These hypotheses will be addressed in the experiments of the two Specific Aims: (1) to optimize using medicinal chemistry approaches to create more effective compounds; and (2) to evaluate the effectiveness of RAD51 inhibitors in a mouse GBM model. 

Lan Hoang-Minh, PhD

Institution: University of Florida

Mentor: Duane A. Mitchell, MD, PhD

Tribute: Supported by Humor to Fight the Tumor

 Despite decades of research, the prognosis for pediatric and adult patients diagnosed with glioblastoma and medulloblastoma remains poor, and novel treatment strategies are urgently needed. Harnessing patients’ own immune system has immense potential for cancer treatment. Among cancer immune therapies, adoptive T cell therapy (ACT), in which patient-derived immune cells are activated against tumor cells, multiplied, and then reintroduced into patients, is particularly promising. In preclinical as well as clinical studies at our institution, ACT has shown increased effectiveness over standard therapies in treating aggressive brain tumors. The success of ACT for brain cancers necessitates innovative approaches that increase T cell trafficking to brain tumor sites, as well as biomedical imaging modalities that enable the non-invasive monitoring of transferred T cell accumulation and persistence in the tumors, thus avoiding the need for serial biopsies.

Our project seeks to optimize ACT in new, clinically relevant preclinical models of recurrent glioma and medulloblastoma, while pioneering the application of novel and non-invasive magnetic particle imaging technology for the tracking of transferred T cells. Our studies will provide a better understanding of ACT dynamics and help optimize immunotherapy strategies against malignant brain tumors. Importantly, the development of magnetic particle imaging could lead to non-invasive treatment monitoring in patients, as several clinical scanners are rapidly being developed.

Gary Kohanbash, PhD

Institution: Children’s Hospital of Pittsburgh of UPMC

Mentor: Ian Pollack, MD

Tribute: Supported by Southeastern Brain Tumor Foundation

Immuno¬therapy is only moderately effective against deadly gliomas. Glioma tumors are full of myeloid cells that help the tumor grow and block immune response to immunotherapy. Myeloid cells are cells of the immune system that are supposed to defend the body against foreign invaders, including cancer cells.

We recently found an antibody that binds to myeloid cells in the tumor. We propose to attach a radioactive element to that antibody to kill tumor myeloid cells, and also deliver radiation to the tumor. Non-invasive imaging will be used to monitor tumor shrinkage and/or progression. We believe this novel approach can be a safe and highly effective way to increase the power of immunotherapy to treat glioma in adults and children.

Basic Research Fellowship

The Basic Research Fellowship is a two-year, $100,000 grant, awarded to post-doctoral fellows who are mentored by established and nationally-recognized experts in the neuro-oncology field.

Emily Darrow, PhD

Institution: St. Jude Children’s Research Hospital

Mentor: Paul A. Northcott, PhD

Medulloblastoma is a common and deadly brain cancer diagnosed in children. Despite advances in therapy, an unacceptable number of affected children will either lose their battle to cancer or suffer severe long-term side effects from current treatment. Medulloblastoma is no longer considered a single disease and can be split into four distinct groups on the basis of biological and clinical differences. These medulloblastoma groups, known as subgroups, are believed to originate from different cell types in the brain of the developing child. During development, our genes respond to a series of environmental cues that ultimately give cells their identity and unique functionality. This process is controlled in part by proteins known as chromatin modifiers that regulate which genes are active and when.

Mutations in chromatin modifiers are especially common in Group 4 medulloblastoma; however, studies investigating the molecular consequences of these mutations and how they contribute to cancer development are largely lacking. The overall aim of this proposal is to determine how specific chromatin modifier mutations convert normal cells of the developing brain into Group 4 medulloblastoma cancer cells.

To achieve our research objective, we will apply state-of-the art molecular techniques to medulloblastoma patient samples and model systems. This research will advance our understanding of Group 4 medulloblastoma biology and provide more effective treatment options for affected children.

Tyler Miller, MD, PhD

Institution: Massachusetts General Hospital

Mentor: Bradley Bernstein, MD, PhD

Tribute: In honor of Joel A. Gingras, Jr.

I believe the best chance of a cure for aggressive brain tumors is to harness the immune system. Cancer immunotherapies require T-cells to migrate into a tumor and maintain their killing ability. T-cells are a type of immune cell that helps to create immunity to a specific foreign particle such as a signal on a cancer cell.

Brain tumors are packed with myeloid cells that should kill tumor cells and recruit T-cells; however, the tumors reprogram these myeloid cells to an immunosuppressive state, preventing T-cell migration and function. My aim is to revert tumor-associated myeloid cells to an anti-tumor state; for effective immunotherapy for brain tumor patients. To do this, I must characterize the functions and origins of immune cells in brain tumors. I have developed methods to simultaneously analyze gene expression, genetic mutations, and protein markers in single cells at massive scale, and am using these technologies to deeply characterize the immune microenvironment of brain tumors at unprecedented resolution. I am using these data to predict new therapeutic strategies that could kill or reprogram immunosuppressive macrophages. In this proposal, I am testing these new interventions using a recently developed brain tumor organoid model that maintains all of the tumor microenvironment, including immune cells.

This revolutionary model system allows me to test therapeutic strategies on patient-specific human myeloid cells, interacting with human T-cells and cancer cells outside the human brain, something previously not possible. It also allows me to test many more therapeutic strategies than is possible in a mouse model. Using this new model system, I hope to accelerate the discovery of transformative therapies that harness the immune system to attack brain tumor and extend survival for patients.