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 $477,000 in grants to 18 new projects
    • $450,000 funded 9 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

2022 Newly Awarded Grants

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.

 

Shreya Budhiraja, BA

Institution: Northwestern University 

Mentor: Atique Ahmed, PhD 

Tribute: Supported by BrainUp

Glioblastoma (GBM) is a form of brain cancer that affects 12,000 adults in the US every year. Treatment usually involves surgical resection, followed by radiation and chemotherapy. Unfortunately, despite such invasive treatment, the average survival is only a year after diagnosis.

This poor prognosis seems to be due to GBM’s inherent aggressiveness; the reason for which remains largely unknown. To determine which genes are responsible for this aggressiveness, our lab performed a genome-wide screen in GBM cells. From this screen, we identified one gene in particular, THOC1, that was found to drive this aggressiveness. Although previously unstudied in GBM, THOC1 is known to prevent deadly structures called R-loops from forming on DNA.

R-loops: naturally occurring structures on DNA where RNA binds for normal cell functions. However, when R-loops accumulate in certain areas across the genome, they can cause in breaks in the DNA, resulting in cell death.

We hypothesize that THOC1 may be driving GBM aggression by preventing these harmful R-loops from forming specifically on the ends of DNA. Since the ends of DNA, called telomeres, need to be especially protected for cancer to be aggressive, targeting THOC1’s protective force could be a way to kill GBM cells. In this study, we will:

  • investigate the link between THOC1 and R-loops on telomeres, and
  • assess the efficacy of the drug luteolin, a THOC1 inhibitor, which may be able to increase these toxic R-loops, kill GBM cells, and prolong survival.

Overall, these findings will reveal crucial insight into an unknown mechanism of GBM aggression, providing a novel therapeutic approach for a disease desperately in need of effective therapies.

Eric Chalif, BA

Institution: University of California, San Francisco

Mentor: Manish Aghi, MD, PhD

Tribute: Supported by Southeastern Brain Tumor Foundation 

Glioblastoma (GBM) is the most aggressive primary brain cancer, and despite a standard of care for patients that includes maximal safe resection followed by chemotherapy and radiation, the prognosis is still grim. Unfortunately, new classes of medications such as immune checkpoint inhibitors that have revolutionized treatment for cancer outside of the Central Nervous System have so far been unsuccessful in clinical trials for GBM.

However, drugs that activate the immune system by other means remain particularly promising candidates for the treatment of GBM due to its marked local and systemic immunosuppression. These mechanisms of immunosuppression are diverse and often redundant, which makes targeting any one agent insufficient to completely overcome the suppressive state. It is likely that combinatorial immunotherapy will be necessary in the development of successful regimens. Costimulatory molecules such as GITRL, OX0-40L,and 4-1BBL may be key agents in future therapeutic cocktails. Targeting these molecules’ receptors have already shown promise in clinical trials for a variety of solid cancers and in preclinical models of glioblastoma.

In this study, we will develop four new viral therapies, validate their function, and test their utility in a mouse model of GBM. Our findings will enable future studies in targeted immunotherapy, and they signify an exciting step towards the future development and refinement of new therapeutic approaches in human clinical testing.

Stephen Frederico, MS

Institution: Children’s Hospital of Pittsburgh

Mentor: Gary Kohanbash, PhD

Tribute: In memory of Jeffrey Ragan Frost

Tumors of the brain and spinal cord are the most common cancer in children and the leading cause of cancer-related death in children. Two of the deadliest brain tumors in children are diffuse intrinsic pontine glioma (DIPG) and pediatric high-grade glioma (pHGG), which have an average five-year survival of 2% and 20% respectively. Often, these tumors cannot be entirely surgically removed, and they respond quite poorly to chemoradiation. Due to these factors, the time is now to design new therapies to treat these diseases.

Fortunately, DIPG and pHGG can be safely targeted by the immune system using immune-cells called T-cells which can be modified from a patient’s blood to recognize these tumors. Our research group intends to modify T-cells by adding a receptor (a type of naturally occurring protein) that can allow them to identify the tumors and eliminate them, while sparing healthy cells. Once we have successfully modified T cells, we will grow large numbers of them and then administer them to patients.

This summer I intend to perform the experiments necessary to add the receptors to T cells and verify that the approach is successful. Thereafter, I will verify that these modified T cells kill tumor cells in the lab. This work will be a crucial step in verifying the functionality of our modified T cells before proceeding to animal and patient studies.

 

David Hou, BA

Institution: Northwestern University

Mentor: Catalina Lee-Chang, PhD

Tribute: In Honor of Paul Fabbri

Glioblastoma (GBM) is a deadly brain cancer with a current survival of only 15 months despite standard of care. Immunotherapy, which utilizes the body’s own immune system to target the cancer, is a promising new approach to treating GBM that has shown significant efficacy in many other cancer types. The utilization of a type of immune cells, called B cells, as an immunotherapy is a novel approach, and we previously showed our B cell based vaccine (Bvax) can result in a very potent survival benefit in preclinical GBM models. The goal of this study is to investigate the underlying mechanisms of our B cell vaccine to both improve our current vaccine as well as develop novel immunotherapy strategies against GBM.

We hypothesize that a major function of Bvax is to activate CD8+ T cells (another type of immune cell) which can then directly kill tumor cells. During this activation process, these CD8+ T cells take on a memory profile which allows them to survive long-term in the tumor environment. Bvax also boosts the metabolic fitness of CD8+ T cells which helps them survive in the tumor environment that lacks oxygen and nutrients for these CD8+ T cells to carry out their functions. The aims of this project include identifying signaling pathways that Bvax uses to activate CD8+ T cells, characterizing the metabolic profile of Bvax-activated CD8+ T cells, and translating these CD8+ T cells into an additional novel therapy.

 

Kyle McGrath, BS

Institution: University of Florida

Mentor: Maryam Rahman, MD

Tribute: In memory of Brian Bouts

About 12,000 adults are diagnosed with glioblastoma (GBM) each year, and only about 5% of these patients will still be alive 5 years after their diagnosis. Since the prognosis of GBM remains poor and not all patients are able to undergo surgery, new treatments are desperately needed. Leveraging our experience with mRNA-based vaccines, we have developed a novel method of delivery of mRNA that results in potent anti-tumor immune responses in mouse models of GBM. Using a combination of additives to stabilize the vaccine and activate immune cells, including hydrogel, chemokines and lipid nanoparticles, a large amount of mRNA can be delivered that results in activation of a diverse population of immune cells. Vaccination with the hydrogel-chemokine-mRNA (HCM) vaccine results in immune cells called natural killer (NK) cells to be activated. These NK cells contribute to the reprogramming of the tumor microenvironment. This research proposal will further investigate the mechanisms by which NK cell activation at the site of the vaccine delivery results in immune changes within the tumor. As current vaccine therapies are not able to elicit a strong enough response against tumor growth, understanding this mechanism could help improve on current GBM vaccine therapeutics to increase patient survival.

Khashayar Mozaffari, BS

Institution: University of California, Los Angeles

Mentor: Isaac Yang, MD

Tribute: Supported by The Gladiator Project

Glioblastoma (GBM) is the most common and aggressive brain tumor with an extremely poor prognosis despite advancements in diagnostics and management. Abnormal vascularization is the disorganized growth of blood vessels that occurs in aggressive tumors and is a prominent feature of GBM, contributing to its dismal prognosis. This vascularization process is predominantly performed by a soluble protein named vascular endothelial growth factor (VEGF). Although targeting the VEGF signaling pathway is theoretically a suitable treatment approach, many anti-VEGF agents have failed to provide any meaningful improvement in patient survival. Therefore, it is crucial for the scientific community to investigate novel targets that are involved in pathological vascularization of these tumors.
One potential novel target is epithelial membrane protein-2 (EMP2), a protein that has shown to play an important role in GBM. In this project, we aim to evaluate the efficacy of anti-EMP2 therapeutic agents with other anti-vascularization agents on GBM 3D organoid cultures created from patients’ tumors. Organoids replicate the tumor’s microenvironment more accurately. Therefore, we anticipate that our results will translate to clinically applicable findings and, if successful, lead to a new therapeutic option for GBM patients.

 

 

 

Janet Wu, BA, BM

Institution: Stanford University  

Mentor: Michael Lim, MD 

Tribute: In memory of Jeffrey Michael Tomberlin

Glioblastoma (GBM) is the most aggressive form of brain cancer that patients currently face. Improvements in patient survival have been small over the past several decades. STING agonist drugs, or treatments that help to stimulate the immune system, present an exciting new class of immunotherapies that holds potential to induce effective antitumor immune responses. Immune system cells, particularly macrophages and myeloid-derived suppressor cells, are a major barrier to inducing immune responses. With this project, we aim to decipher the mechanisms of STING agonist drugs to oppose myeloid-induced suppression of the immune system.

We propose that STING agonist drugs will increase antitumor immune responses by improving dendritic cell (a type of immune cell) function, which we will assess by using a mouse model of GBM. We will extract dendritic cells from these mice and quantify how well they can perform two major functions: detecting the presence of tumor cells and activating T cells, a type of immune cell that can target and kill tumor cells if activated properly. We hope that our findings from this study will provide the necessary preclinical data to apply STING agonist drugs to human studies and clinical trials.

2020 & 2021 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.

 

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. 

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.

DebnathLeadPIph

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.