Dr. Jeffrey Greenfield: Pediatric Neuro-oncology

Dr. Jeffrey Greenfield, Weill Cornell Medicine Neurosurgeon

Dr. Jeffrey Greenfield, co-director of the Children’s Brain Tumor Project at Weill Cornell Medicine, directs a pediatric neuro-oncology research laboratory with the goal of better understanding brain tumors that primarily strike children, adolescents, and young adults.

The laboratory team is currently conducting research efforts on three fronts:

Genomic Sequencing
In 2011, Dr. Greenfield and his research team completed the first-ever sequencing of a gliomatosis cerebri tumor, revealing vast amounts of genomic data about this rare cancer. (The patient, Elizabeth Minter, went on to found Elizabeth’s Hope with her family, friends, and Dr. Greenfield before losing her battle with the tumor in 2012.) In Dr. Greenfield's research lab, the team focuses on genomic sequencing to better understand pediatric brain tumors in a quest to identify the best therapeutic agents for each one.

Like other inoperable pediatric brain tumors, gliomatosis cerebri is extremely diffuse and does not behave like adult gliomas. It’s also very uncommon, making it difficult to study since there simply aren’t enough cases to provide a wide range of samples. That makes it even more important to conduct genomic sequencing, to extract the maximum information possible from a small number of samples.

Since no one institution will see many patients with these rare tumors, collaboration is key to Dr. Greenfield’s research. Dr. Greenfield’s lab has become known as a major center of investigation into gliomatosis and other rare pediatric tumors, and recently launched the Gliomatosis Cerebri International Registry. Tumor tissue and blood samples are shared through a national network of research centers and hospitals, and a worldwide database of patient data is being created through the Registry.

Mechanisms of Tumor Neo-Vascularization
Dr. Greenfield’s lab team is studying the functions of stromal cells and bone-marrow-derived cells in angiogenesis and progression of pediatric brain tumors. Low-grade gliomas grow slowly, and individuals diagnosed with these tumors can live for decades. But high-grade lesions are extremely aggressive, and their rapid proliferation means that a patient usually survives less than two years from diagnosis.

High-grade gliomas grow quickly because they develop an almost boundless blood supply. A vast network of new blood vessels form at the tumor site in a process called neovascularization, fed by signals from the bone marrow and allowing the tumor to double and redouble in size. This summer’s project aims to block those signals and prevent neovascularization.

In Dr. Greenfield’s lab, researchers are using mouse models to study the effects of an inhibitor drug on the progression of gliomas. Using special stains to track which types of cells are mobilized as the tumor grows, and comparing disease progression in treated versus untreated mice, researchers hope to be able to show that the bone marrow is indeed “recruiting” the cells that drive those new blood vessels to form, and that using inhibitor drugs can successfully delay disease progression by impeding this process.

Mediated Oncogenesis in Pediatric Brain Cancers
We are conducting this project in collaboration with The Rockefeller University and Memorial Sloan-Kettering. C. David Allis, PhD, of The Rockefeller University is the Principal Investigator; Dr. Greenfield is one of the co-principal investigators. The project is investigating how histone H3.3 mutations affect the epigenetic landscape to mediate the development of pediatric gliomas. The goal of the study is to generate novel insight about pediatric gliomagenesis, streamline clinical translation of pediatric glioma treatment, and identify novel therapeutic strategies.

Dr. Greenfield's lab is a part of the Children's Brain Tumor Project at Weill Cornell Medicine Neurological Surgery. The Children’s Brain Tumor Project is supported by families and friends due to lack of government funding. Find out how to make a donation to help advance the science of pediatric brain tumors.

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