Brain and Central Nervous System Tumors

Current Projects
Zulekha A. Qadeer, PhD

Dr. Qadeer investigates the mechanisms underlying medulloblastoma (MB), the most common form of malignant brain tumors in children. Group 3 MB is a particularly aggressive subgroup, for which there are few actionable targets for therapies. Dr. Qadeer aims to understand how the genes and pathways regulated by the proteins MYC and TGFb mediate the transformation of neural precursor cells to malignant group 3 MB tumors. This work may also help elucidate tumor heterogeneity and resistance to current alkylating chemotherapies. The overall goal of this research is to identify more effective therapies to treat patients by targeting the mutations that drive tumor formation.

Project title: "Targeting TGFb pathway dependencies in Group 3 Medulloblastoma" 
Institution: University of California, San Francisco
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): William A. Weiss, MD, PhD
Cancer Type: Pediatric, Brain
Research Area: Invasion and Metastasis
Jay F. Sarthy, MD, PhD

Dr. Sarthy is developing new easy-to-use and affordable methods for studying DNA packaging and epigenetics (modification of gene expression) in pediatric cancers with a special focus on diffuse midline gliomas and neuroblastoma. These methods may help explain the drivers of pediatric malignancies and allow clinicians to better monitor response to treatment with the goal of developing new drugs that restore the cell’s ability to package DNA correctly.

Project title: "Characterization of the epigenomic landscape of diffuse midline gliomas"
Institution: Fred Hutchinson Cancer Research Center
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Steven Henikoff, PhD
Cancer Type: Blood, Other Cancer, Pediatric, Brain
Research Area: Epigenetics
Kathryn R. Taylor, PhD

Dr. Taylor is investigating the impact of neural activity on pediatric high-grade glioma (pHGG) invasion. The innate ability of pHGGs to diffusely infiltrate healthy brain tissue is a classical hallmark of the disease, which represents a major contributor to the devastating prognosis. Using optogenetic techniques to stimulate neuronal activity, she will directly and noninvasively test the effect of activity-dependent secreted proteins on tumor cell invasion in human cancer cells and animal models. She plans to confirm the pro-infiltrative effect of candidate proteins on pHGG and subsequently uncover the mechanisms by which they alter the molecular dynamics of the tumor cell. Her hope is to highlight a novel means by which the neural microenvironment drives glioma progression and most importantly identify a new set of therapeutic targets to limit glioma spread.

Project title: "The effect of neuronal activity on pediatric glioma invasion"
Institution: Stanford University
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Michelle L. Monje, MD, PhD
Cancer Type: Other Cancer, Pediatric, Brain
Research Area: Developmental Biology
Kouki Touhara, PhD
Project title: "Investigating chemical signaling between gut enteroendocrine cells and intrinsic primary afferent neurons"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): David Julius, PhD
Cancer Type: Brain
Research Area: Endocrinology
Jingyi Wu, PhD

Dr. Wu is studying the epigenetic profile of glioma brain tumors at single cell resolution. Epigenetic alterations, which change gene expression without any changes to the underlying DNA sequence, can affect cancer driver genes in many tumor types, including gliomas. Unlike genetic mutations, epigenetic alterations are often reversible and are promising drug targets. Dr. Wu aims to determine whether there are various subpopulations of cells with distinct epigenetic features within a tumor, and whether the epigenetic differences endow these subpopulations with distinct properties, such as propensity for growth or drug resistance. These studies will lay the groundwork for precision treatment strategies targeting the fast-growing and drug-resistant cells within gliomas, and potentially other tumor types.

Project title: "Epigenetic clonal evolution in gliomas"
Institution: Massachusetts General Hospital
Award Program: Fellow
Sponsor(s) / Mentor(s): Bradley Bernstein, MD, PhD
Cancer Type: Brain
Research Area: Chromatin Biology
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