Research Funding & Impact

Research Funding—2020

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 $368,000 in grants to 11 new projects
    • $200,000 funded 2 Basic Research Fellowships
    • $150,000 funded 3 Discovery Grants
    • $18,000 funded 6 Medical Student Summer Fellowships
  • The 2020 funded projects span multiple tumor types:
    • Atypical Teratoid/Rhabdoid Tumor
    • Glioblastomas
    • Malignant Gliomas
    • Medulloblastomas
  • Research areas of focus:
    • Drug Therapies/Experimental Therapeutics
    • Epigenetics
    • Immunology/Immunotherapy
    • Gene Expression/Transcription
    • Stem Cells

ABTA-Funded Research Projects

2020 Newly Awarded Grants

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

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.

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.

Lan Hoang-Minh, PhD

Institution: University of Florida

Mentor: Duane A. Mitchell, MD, PhD

 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.

Jack & Fay Netchin Medical Student Summer Fellowship

A Medical Student Summer Fellowship is a 10 to 12 week mentor-guided summer research experience, intended to motivate talented medical students to pursue a career in neuro-oncology research.

Hasan Alrefai, BS

Institution: University of Alabama at Birmingham

Mentor: Christopher Willey, MD, PhD

Tribute: In memory of George Surgent

Glioblastoma multiforme (GBM) is the most common and deadly brain cancer. There are currently no curative treatments available; therefore, there is a need for improved understanding of GBM biology. In this research project, we will work with MED2, a protein therapy that selectively targets and kills the GBM cells responsible for resistance to radiation and chemotherapy, while leaving normal, healthy cells relatively unaffected.

Under normal conditions, GBMs attract microglia to the tumor site and modify their immune function.

Microglia: Specialized immune cells found in the brain and central nervous system.
Once microglia go to the tumor, the GBM manipulates them to produce growth factors that help the GBM to grow and spread. Little is known about MED2’s effects on microglial recruitment and modification. 

In this project, we propose to achieve the following aims:

1) To investigate MED2’s effects on microglial survival and
2) To investigate MED2’s effects on microglial function to block or promote tumor growth.

This study will provide us insight into how MED2 impacts the cells surrounding GBM that help it to grow and spread. Having a more complete understanding of how MED2 works will help us better develop therapies that may one day enter the clinic to improve outcomes in GBM.

Ian Burns

Institution: McMaster University

Mentor: Sheila Singh, MD, PhD, FRCS(C), FAANS 

Tribute: In honor of Davvy Lila Netchin

Medulloblastoma (MB) is the most common brain cancer in children. Although 75% of affected patients live longer than 5 years after diagnosis, a subset of patients develop secondary cancers that are essentially incurable. Our lab has previously shown these types of MB tumors contain a large number of cancer cells that are similar to stem cells, and therefore resist standard therapies. We aim to better understand how these cells are able to survive through cancer treatment in order to develop new ways to eliminate them.

We have identified a protein, Bmi1, in the MB stem cells that helps them jump-start tumor growth after they have spread to other parts of the central nervous system. When we block the function of Bmi1 in MB preclinical models and then treat with standard therapy, we are able to drastically reduce their cancer. However, the cancer eventually returns.

We have generated a preliminary list of other genes/proteins that work with Bmi1 to keep these tumor cells from being killed by the standard treatment regimen. We now aim to confirm the role of several of these genes/proteins and eventually develop a multi-drug therapy paradigm that can effectively kill these resistant MB cancer cells.

Andy Ding, BA

Institution: Johns Hopkins University School of Medicine

Mentor: Henry Brem, MD

Tribute: In honor of Paul Fabbri

Atypical Teratoid/Rhabdoid Tumor (ATRT) is a rare but highly aggressive brain tumor that is most commonly found in infants and young children. Historically, ATRT has been a difficult cancer to treat, despite efforts with surgery, radiation, and chemotherapy. Even if treatment is successful in eliminating the cancer, ATRT tends to recur at an average time of 6 months after initial treatment. Radiation therapy has been particularly difficult to use for ATRT, due to potential long-term effects on brain development when administered to children younger than 3 years of age. Due to the robust treatment-resistance exhibited by ATRT, patients tend to succumb to their disease at an average time of 12-18 months after diagnosis. Furthermore, since treatments have largely been unsuccessful, there is no current agreement for a standard treatment for ATRT.

Previous studies have shown that ATRT depends on a protein called cyclin D1 for tumor development and growth. Levels of cyclin D1 in ATRT depend on other cellular components called cyclin-dependent kinases (CDKs).

  • Cyclin D1 and Cyclin-dependent kinases: Proteins in cells that help control cell division and therefore, tumor growth.

This proposal seeks to evaluate the drug TG02, which inhibits CDKs and has the potential to block  the effects of cyclin D1. We propose to study this in three aims:

  1. To examine the effects of TG02 on ATRT cells using human ATRT cells in culture.
  2. To study TG02 effects on ATRT tumors in preclinical models.
  3. To examine the effects of TG02 on sensitization to radiation therapy for ATRT.

Because TG02 has minimal side-effects and may sensitize ATRT cells to radiation therapy, TG02 offers a unique and compelling therapeutic option that addresses crucial obstacles in the treatment of ATRT with radiation and chemotherapy.

Emily Lavell, MHS

Institution: Mayo Clinic in Jacksonville, Florida

Mentor: Hugo Guerrero-Cazares, MD, PhD

Tribute:  Supported by Southeastern Brain Tumor Foundation

Glioblastoma is the most common and aggressive primary brain tumor in adults, with an average survival rate of 14 months after diagnosis. Tumor recurrence is common, due to a combination of treatment resistance and tumor invasiveness. It has been found, in particular, that glioblastomas are more aggressive when they grow in regions of the brain that normally give rise to healthy stem cells. Preliminary evidence from Dr. Hugo Guerrero-Cazares’ lab indicates that communication between brain tumor cells and stem cells via extracellular vesicles (EVs) may contribute to this increased aggressiveness.

  • Extracellular vesicles: Small envelopes containing messages, in the form of functional proteins and nucleic acid molecules, that cells use to communicate with other cells.

Therefore, in my project, I will explore the role of EVs by blocking their release out of the cell using a drug called chloramidine. If the use of chloramidine successfully blocks cell-to-cell communication by glioblastoma cells and results in a decreased cancer malignancy, this could lead to a new way to treat patients with GBM and other brain cancers.

Brian V. Lien, BS

Institution: University of California Irvine School of Medicine

Mentor: Daniel Lim, MD, PhD

Tribute: In memory of Katie Monson

Glioblastoma (GBM) is the most common and aggressive primary brain tumor and is rapidly fatal. Radiation therapy is nearly always prescribed for patients with GBM. There is an unmet need for cancer therapies that enhance the therapeutic effects of radiation therapy while minimizing toxicity to normal brain tissue. Using a CRISPR-based strategy and next generation sequencing, we screened thousands of long non-coding RNAs (lncRNAs) expressed in GBM cells, identifying lncGRS-1 as a promising novel drug target.

  • CRISPR: A gene editing technology.
  • lncRNA: A type of RNA molecule in cells that can control many functions in the cell by regulating the production of other molecules.

 Antisense oligonucleotides (ASOs) are used in gene therapy to modify an RNA molecule of interest and are currently FDA-approved for use in neurological diseases.

  • Antisense oligonucleotides (ASO): synthetic molecules that can block specified RNA molecules in cells.

We have found that blocking lncGRS-1 using ASOs can slow GBM cell growth without toxicity to normal human brain cells. While there is evidence that lncGRS-1 is a potentially useful therapeutic target, its function and molecular mechanism remain poorly understood. The goal of my proposed summer research project is to understand the mechanism of action of lncGRS-1 at the molecular level by examining a variety of ways that lncGRS-1 may interact with other components of the genome, using gene editing, ASOs, and chromosome conformation capture.

Edith Yuan, BA

Institution: Keck School of Medicine – University of Southern California

Mentor: Frank Attenello, MD

Tribute: In memory of Rose DiGangi

Glioblastoma (GBM) is the most common and aggressive brain tumor. Despite current treatments, the prognosis for GBM remains poor, with the average survival rate of 15 months. Treatment for GBM is not only medically challenging, but the disease also brings immense emotional distress to patients and their families. Because of this, our lab is motivated in studying new therapies that will help combat the aggressiveness of GBMs.

 Studies have shown that patients with an overabundance of certain lncRNAs tend to have lower rate of survival. Therefore, in this project, I will investigate long non-coding RNAs (lncRNAs) as a potential target for GBM therapies.

  • lncRNA: A type of RNA molecule that can control many functions in the cell by regulating the production of other molecules.

The goals of our project are to:

  1. Study the effects of suppressing specific lncRNAs on tumor cell invasiveness and proliferation (when cells multiply by making copies of themselves).
  2. Test if an established, pharmacological method of blocking the production of specific RNAs can effectively suppress the lncRNAs that contribute to GBM progression.

We believe that by preventing the expression of specific lncRNAs, there will be a decrease in GBM aggressiveness and thus, an improvement in patient survival.

2019 - 2021 Ongoing Projects

Research Collaboration Grant

The Research Collaboration Grant is a two-year, $200,000 grant, designed to support a multi-PI, multidisciplinary project that can accelerate advances in the understanding and treatment of brain tumors through collaborative team science.

Justin Lathia, PhD

Institution: Cleveland Clinic

Co-Pl: Joshua Rubin, MD, PhD

Co-Pl Institution: Washington University in St. Louis

Tribute: In memory of Victor Perez Maldonado

Advances in medicine emerge from prospective clinical trials, which allow patients with a given disease and meeting specific eligibility criteria to access studies that provide a controlled assessment of a therapy. This eligibility practice, while controlled, has largely ignored the possibility that female and male patients with glioblastoma, a highly malignant form of brain cancer, differ in incidence rates and outcome.

In the present era of Precision Medicine, sex of the patient, which is linked to incidence and survival, is not used to personalize care for glioblastoma.

Our preliminary and published studies uncovered a remarkably better response to standard care in female glioblastoma patients than in male patients as well as sex-specific differences in signaling networks and interactions in the tumor microenvironment.

In this project, we will utilize animal models that allow us to distinguish between the contribution of sex hormones and that of sex chromosomes to determine changes in signaling pathways and alterations in microenvironmental interactions by using a real-time in vivo imaging platform.

Our studies will demonstrate a paradigm for sex-specific approaches to personalized medicine in glioblastoma. Progress in our studies will establish a model approach for future studies that take into account sex as a biological variable in cancer care.

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.

Javier Ganz, PhD

Institution: Children’s Hospital Boston

Mentor: Christopher A. Walsh, MD, PhD

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

Understanding how brain cancer starts requires studying the brains of normal people, and trying to figure out where and how the earliest mutations arise that might lead to cancer years later. Our preliminary data suggest that young healthy people already harbor cells in their brain showing mutations that we know drive brain cancer. How do these early mutations arise? Such somatic mutations can be acquired during prenatal development or later in life, but are usually not inherited from the parents. Acquisition of these mutations by normal cells can lead to microscopic abnormalities starting years before detectable tumors appear. By studying the occurrence of early cancer mutations in normal brains, we will establish a roadmap of early-occurring processes that precedes cancer initiation. Brain tumors in general are derived mostly from glial cells, astrocytes and oligodendrocytes, but not neurons. We developed a method that, for the first time, is able to study the complete genome of glial cells and see how they accumulate somatic mutations, starting from fetal life and through older stages. By studying this at the single cell level, will give us a unique opportunity to obtain information with unprecedented resolution, no attainable by any other means. This research will be the first of its kind, improving our understanding of brain tumor initiation but also in providing the basis for developing sensitive methods for detecting incipient tumors where no manifestation is evident.

Maria Garcia Fabiani, PhD

Institution: University of Michigan

Mentor: Maria Castro, PhD

Tribute: In memory of Bruce and Brian Jackson

This project relates to a sub-type of pediatric malignant glioma (pHGG) that is currently incurable. This tumor is found predominantly in the adolescent population and patients have a median survival of 18 months post diagnosis. The extrapolation of tested chemotherapeutics and targeted agents from adult HGG failed to improve the clinical outcome in the pediatric population, so the availability of a reliable experimental model is imperative for the testing of new therapies specifically designed for this type of tumor. The experiments proposed will shed light on many aspects of the tumor’s biology. We are interested in studying: 1) the role that the immune system plays in tumor progression and malignancy 2) and how we could harness it to test therapeutic modalities. To achieve this, we have developed a pHGG mouse model that mirrors the human disease and is a valuable tool to complete the proposed experiments. Having a mouse model to study this disease will allow us to explore many aspects of this type of tumor and possible therapies. The lab where I work has a strong background in brain cancer research and immune-therapeutics of cancer and offers an extraordinary working environment that will allow me to unravel key aspects of this tumor which currently remain unknown. We expect to provide compelling evidence to gain new insights on the biology of this subtype of pHGG which will lead to the development of novel immune-mediated targeted therapies.

Albert Kim, MD

Institution: Massachusetts General Hospital

Mentor: Elizabeth Gerstner, MD

Tribute: In honor of Paul Fabbri

Brain metastases (BM) are the most common tumor within the brain and carry a poor prognosis due to limitations in current treatment options. This is a critical unmet need, as the incidence of BM is rising as treatment for systemic cancer improves. Recent promising studies demonstrate that immune checkpoint inhibitors (ICI) can induce objective intracranial response. This response is unpredictable and often not durable. Further compounding this conundrum is the difficulty in accurately assessing response, as an increase in contrast enhancement on standard post-contrast MRI can be seen in treatment-related changes and true tumor progression. These challenges highlight the need for noninvasive biomarkers that reflect the biological response to ICI, as it is not feasible to obtain serial brain biopsies to understand why some patients benefit and others do not. Here, we leverage two novel, complementary approaches – perfusion MRI and circulating tumor DNA from blood and CSF – to understand the longitudinal changes within the tumor environment as a result of ICI. Our proposal is an unprecedented opportunity specifically tailored to patients with BM in which we will obtain detailed tumor blood vessel changes and the genomic basis for such changes during treatment. We seek to identify reasons why ICI ultimately fail, and specific patterns that predict response to ICI. This will result in optimization and better patient selection for these promising treatments.

Thi Thu Trang Nguyen, PhD

Institution: Columbia University

Mentor: Markus Siegelin, MD

Tribute: In memory of Katie Monson

Glioblastoma is the most common primary brain tumor with a current life expectancy of 12-15 months. In this proposal, the applicants propose a novel treatment strategy for glioblastoma. Using preclinical models, the investigators are evaluating a combination therapy of two clinically validated drug compounds, BH3-mimetics as well as a certain class of cholesterol lowering compounds that were recently shown to be efficacious in model systems of GBM. We are studying the mechanism by which this drug combination works, which has informed and led us to the proposed strategy. Using the most advanced model system resembling human disease, we will be studying this drug combination in “patient-derived xenograft” model systems. The results of these studies will allow us to propose clinical studies, involving this novel drug combination. In this context, it is noteworthy that both compounds have already entered clinical testing, enabling quicker access to patient application.

Jan Remsik, PharmD, PhD

Institution: Memorial Sloan-Kettering Cancer Center

Mentor: Adrienne Boire, MD, PhD

Tribute: Supported by an Anonymous Corporate Partner

Leptomeningeal metastasis (LM) or spread of cancer cells into the spinal fluid is increasingly common and results in rapid neurologic disability and death. Colonization of leptomeningeal space by cancer cells can take years or even decades after primary cancer diagnosis. The molecular basis of this process remains virtually unknown. Working from our observations from patient samples and unique experimental mouse models, we will dissect the mechanism of cancer cell entry to the spinal fluid using cutting-edge technologies. Moreover, the presence of fully functional immune system in our novel syngeneic mouse models enables us to target immune pathways essential for development and progression of LM. Our approach will rationalize the application of immune therapies, employing the patient’s own immunity as an active weapon against disseminated cancer cells.

Anh Tran, PhD

Institution: Northwestern University

Mentor: Craig Horbinski, MD, PhD

Tribute: In honor of Ned Smith and Team Smith Strong

Glioblastoma (GBM) is an aggressive form of brain cancer with no cure and few treatment options. Increased activation of receptor tyrosine kinases (RTKs), especially epidermal growth factor receptor, (EGFR) has been well-characterized in GBM. However, drugs that only targeting RTKs have limited efficacy on GBM patients. Our preliminary data show that tissue factor (TF), a protein normally involved in blood clotting, is increased in GBM and can activate many RTKs, even with RTK inhibitor treatment. TF does this through another protein called protease-activated receptor 2 (PAR2), and we found that we could block TF and PAR2 with drugs to decrease GBM malignancy. Furthermore, blocking these proteins also suppress brain tumor-initiating cells, which were known to cause therapeutic resistance and recurrence in GBM. In this study, we will: 1. Investigate how TF and PAR2 interact with and activate RTKs, with the goal to understand how they can help GBM tumors to evade treatments. 2. Determine how TF and PAR2 promote brain tumor initiating cells and test if this effect could be blocked by getting rid of either protein. We will also find the connection between TF, PAR2, RTKs, and tumor-initiating cells. This research will reveal novel targets for GBM therapy and extend our knowledge on the regulation of different factors that contribute GBM malignancy.