Brain and Central Nervous System Tumors

Current Projects
Elisa A. Aquilanti, MD

Without new treatment options, patients diagnosed with glioblastoma brain tumors continue to have poor survival outcomes. Dr. Aquilanti aims to validate a new drug target called telomerase, a protein complex that elongates telomeres that cap the ends of chromosomes. Telomeres shorten with each cell division until they reach a critical length, and the cell stops dividing or dies. Many tumors activate telomerase to prevent the telomeres from shortening so their cells can divide indefinitely. Telomerase activation may be one of the main drivers of glioblastoma, occurring in over 85% of cases. Once she demonstrates that telomerase activity leads to cell death in glioblastoma, she hopes to develop a novel tool for screening drugs that can target telomerase. Additionally, she will explore whether alternative telomere maintenance pathways can develop in response to telomerase inhibition.

Project title: "Targeting telomerase in glioblastoma"
Institution: Dana-Farber Cancer Institute
Named Award: The Ben and Catherine Ivy Foundation Physician-Scientist
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Matthew L. Meyerson, MD, PhD
Cancer Type: Brain
Research Area: Drug Discovery
Amelia N. Chang, PhD

Dr. Chang is investigating the role of activity-regulated gene expression in human brain evolution. Activity-regulated pathways control critical brain functions and modulate tumor growth in multiple cancers. These pathways are broadly conserved across all mammals, but newer studies have identified features that are unique to primates and may influence important aspects of brain function and tumor progression. Dr. Chang will study the function, regulation, and evolution of primate-specific genes. Through these experiments, she aims to uncover molecular insight into what makes humans susceptible to cancer.

Project title: "The role of activity-regulated gene expression in human brain evolution"
Institution: Harvard Medical School
Award Program: Fellow
Sponsor(s) / Mentor(s): Michael E. Greenberg, PhD
Cancer Type: Brain
Research Area: Neuroscience
Erin E. Duffy, PhD

Dr. Duffy is investigating how neuronal activity can regulate gene expression through a potentially novel mechanism in the developing brain, called RNA turnover. This mechanism may enable gene expression to be rapidly and locally controlled at individual connections between neurons based on neuronal activity. There is evidence that neuronal activity may contribute to pediatric malignant glioma brain tumors. Dr. Duffy aims to characterize this process and identify new therapeutic targets for pediatric brain cancer.

Project title: "Activity-dependent changes in RNA stability as a mechanism for synaptic plasticity"
Institution: Harvard Medical School
Award Program: Fellow
Sponsor(s) / Mentor(s): Michael E. Greenberg, PhD
Cancer Type: Brain
Research Area: Neuroscience
Gavin P. Dunn, MD, PhD

Glioblastoma remains the most aggressive brain tumor diagnosed in patients, and it is clear that new treatment strategies are needed. There is significant optimism around the use of approaches that stimulate a patient's immune system to treat brain tumors. Gavin focuses on identifying the specific components of a patient's brain tumor that the immune system recognizes and determining whether there are regional differences in this immune recognition. He hopes that this work will increase our understanding of how the immune system recognizes brain cancers and will increase our understanding of how to rationally design personalized vaccines to treat these tumors. 

Project title: "Characterizing the immunogenic landscapes of malignant brain tumors"
Institution: Washington University
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): John F. DiPersio, MD, PhD, and Robert D. Schreiber, PhD
Cancer Type: Brain
Research Area: Immunotherapy
Rongxin Fang, PhD

Dr. Fang develops multiplexed imaging techniques to illuminate how enhancers control gene expression at a single cell level. Enhancer alterations are widely spread in cancer, but there is limited understanding of how these enhancers vary between single cells and relate to oncogene expression. Dr. Fang will generate single-cell regulatory networks to investigate how enhancer activities are disrupted in IDH-mutant cancers. The proposed work may help identify enhancer-based therapeutic targets for cancer treatment in the future.

 
Project title: Genome-scale imaging of enhancer-promoter interactions in cancer at single cell resolution
Institution: Harvard University
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Xiaowei Zhuang, PhD
Cancer Type: Brain
Research Area: Imaging
Siting Gan, PhD

Dr. Gan focuses on brain metastasis in lung and breast cancer, a major cause of death for these patients. She is applying the latest single-cell technologies and developing computational tools to dissect how tumor cells interact with resident brain cells to mediate the progression of metastasis. This research aims to better understand the formation of brain metastasis which may lead to new therapeutic strategies for prevention.

Project title: "In situ single-cell dissection of the tumor-microenvironment interplay mediating brain metastasis"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Quantitative Biology Fellow
Sponsor(s) / Mentor(s): Joan Massagué, PhD, and Dana Pe'er, PhD
Cancer Type: Brain, Breast, Lung
Research Area: Systems Biology
Pragya Goel, PhD

Dr. Goel is investigating structural and functional aspects of dopamine transmission in the brain, a key neuromodulator for motor and cognitive processes. Dopamine receptors have also been implicated in a variety of cancers, and recent evidence suggests that brain cancer (glioma) cells can form synaptic connections with neurons that drive tumor progression. To better understand the molecular organization that supports dopamine signaling, Dr. Goel will use super-resolution microscopy, modern genetic approaches, and functional measurements to assess the spatial organization of major dopamine receptors and determine the interplay between dopamine release and reception. This research aims to better understand the basic mechanisms of dopamine signaling, which may ultimately enable the design of novel therapies. 

Project title: "Signaling structure for neuromodulatory coding in the vertebrate striatum"
Institution: Harvard Medical School
Named Award: Dale F. and Betty Ann Frey Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Pascal Kaeser, MD
Cancer Type: Brain
Research Area: Neuroscience
Christina L. Hueschen, PhD

Dr. Hueschen studies the motility of Apicomplexan parasites, which cause malaria, foodborne illness (toxoplasmosis) and infections in immunocompromised cancer patients. These parasites move through the human body using a mechanism called "gliding" to migrate over host cells and through the surrounding extracellular matrix. Dr. Hueschen's goal is to understand how molecules inside the parasite are organized, coordinated and regulated to produce forces that direct movement. This research has the potential to aid in the development of therapies to prevent opportunistic infections.

Project title: "Molecular basis and regulation of apicomplexan parasite motility"
Institution: Stanford University
Award Program: Fellow
Sponsor(s) / Mentor(s): Alex Dunn, PhD
Cancer Type: Gastric, Brain, Colorectal, All Cancers
Research Area: Cell Biology
Nagarajan Nandagopal, PhD

Dr. Nandagopal is focusing on genes in the bHLH family and their role in signal integration to help decide whether cells grow and divide, differentiate, migrate, or even die. bHLH genes are involved in fate choices in stem cells of the brain, intestines, skin, and other tissues. They are also commonly misregulated in cancers, such as neuroblastomas and glioblastomas. By comparing signal integration by bHLH circuits in normal and cancer cells, Dr. Nandagopal aims to discover how errors in fate decisions occur, and how they can be corrected. 

Project title: "Signal integration by bHLH circuits to enable cell fate decisions"
Institution: Harvard Medical School
Named Award: Philip O’Bryan Montgomery Jr. MD Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Galit Lahav, PhD, and Sean Megason, PhD
Cancer Type: Other Cancer, Brain
Research Area: Systems Biology
Natasha M. O'Brown, PhD

Dr. O'Brown is investigating the molecular mechanisms that govern the blood-brain barrier (BBB), which acts as the gatekeeper for the brain. While the BBB protects the brain from pathogens and provides the necessary environment for normal brain function, the BBB also acts as an obstacle to drug delivery for the treatment of neurological diseases, including brain tumors. A key regulator of BBB integrity, Mfsd2a, limits transcellular movement across the barrier and therefore prevents leakage into the brain. Using a combination of zebrafish genetics, small molecule screens, and live imaging, she aims to understand how this protein regulates these BBB processes. By investigating the cellular signals that induce or remove barrier properties, she hopes to identify ways by which she can selectively manipulate the barrier to allow for drug delivery to the brain.

Project title: "Molecular and cellular mechanisms of transcytosis regulation in blood-brain barrier function"
Institution: Harvard Medical School
Award Program: Dale Frey Scientist, Fellow
Sponsor(s) / Mentor(s): Sean G. Megason, PhD, and Chenghua Gu, PhD
Cancer Type: Brain
Research Area: Developmental Biology
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