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Funded Research

Ongoing Projects

Evaluation of miRNA-1 as a potential therapeutic target for treatment of chordoma

Zhenfeng Duan, MD, PhD
Sarcoma Molecular Biology Laboratory
Massachusetts General Hospital

$25,000 seed grant

This project builds on our previous observations that chordomas lack an ordinary amount of a regulatory molecule called miRNA-1, which is normally highly expressed in healthy tissues. In this project, we aim to determine how expression of miRNA-1 correlates with clinical variables such as survival. We will also catalogue all of the genes in chordoma cells that are regulated by miRNA-1, to better understand the effect that miRNA-1 deficiency has on chordoma cells. Finally, we will test whether delivering miRNA-1 has an anti-tumor effect in chordoma animal models.

Zhenfeng Duan

Targeting Cancer Initiating Cells with CSPG4-specific mAbs in Chordoma

Soldano Ferrone, MD, PhD
Department of Immunology
University of Pittsburgh

$25,000 seed grant

In this project, we will confirm preliminary observations that chordomas contain a population of cancer initiating cells (also known as cancer stem cells), which are believed to be responsible for causing recurrence and metastasis even after a tumor is removed. Further, we will test whether the combination of an antibody against a protein expressed on chordoma cells, called CSPG4, and an inhibitor of the hedgehog signaling pathway, which is hypothesized to be activated in chordoma, can eradicate chordoma initiating cells both in chordoma cell lines and in a chordoma animal model.

Soldano Ferrone, MD, PhD

Immunotherapy for Chordoma

Michael Lim, MD
Department of Neurosurgery
Johns Hopkins University

$25,000 seed grant

We have previously found that the combination of radiation with an antibody against a protein called PD-1, which cancer cells use to evade the immune system, improves survival and in some cases leads to a cure in mouse models of brain tumors which express a protein called B7-H1. Because chordomas also express B7-H1, we will test this same combination treatment approach in a chordoma animal model. In addition to assessing the ability of the combination to stop tumor growth, we will assess the effect of the treatment on eliciting an immune response to the tumor.

Michael Lim, MD

Cancer Stem Cells in Chordoma: Implications for Tumorigenesis and Treatment

Alfredo Quinones-Hinojosa, MD
Department of Neurosurgery
Johns Hopkins University

$25,000 seed grant

Our team’s long-term goal is develop therapeutic strategies that target stem cell populations of cancers of the neuroaxis. The objective of this application is to determine whether chordomas harbor a population of cancer stem cells responsible for growth maintenance and recurrence. In addition, we will delineate whether the transcription factor brachyury can allow for prospective identification of this cancer stem-like population.

Alfredo Quinones, MD, PhD

Past Projects

A Transgenic Mouse Model of Chordoma

Brian Harfe, PhD
Department of Molecular Genetics and Microbiology
University of Florida

$25,500 grant cofunded with the Liddy Shriver Sarcoma Initiative

Dr. Harfe is a developmental biologist who studies the formation of the spine and intervertebral discs (IVD). In 2008 he conclusively demonstrated that the center of the IVD is derived from notochordal cells, and also discovered that single notochordal cells remain dispersed in the mouse vertebrae through adulthood. Dr. Harfe believes that these notochordal cells are lodged in the vertebrae give rise to chordomas, when a gene called Sonic Hedgehog – which is expressed in notochord but not in IVD - is inappropriately reactivated. He is therefore attempting to spur the development of chordomas in mice by activating Sonic Hedgehog in notochordal cells.

Brian Harfe PhD

Generation of a chordoma mouse model through conditional inactivation of PTEN or TSC1 in the mouse notochord

Vijaya Ramesh, PhD
Center for Human Genetics
Massachusetts General Hospital

$25,000 Model Systems Grant - Transgenic Animal Model

Dr. Ramesh is a molecular-neurogeneticist who studies the function of tumor suppressor genes and genetic tumor syndromes such as Neurofibromatosis and Tuberous Sclerosis Complex (TSC). Dr. Ramesh first reported a possible connection between chordoma and TS in 2004. Since then she and others have discovered that the mTOR pathway, which is regulated by TSC genes, is activated in nearly all chordomas. Therefore Dr. Ramesh and Dr. Harfe are collaborating to develop a mouse model by knocking out two tumor suppressor genes that regulate the mTOR pathway, called PTEN and TSC1, in the mouse notochord. They hypothesize that knocking out these genes will cause the mice to develop chordomas.

Vijaya Ramesh

Generating Chordoma Cell Lines and Xenographs

Adrienne Flanagan, MD, PhD
University College London Cancer Institute and The Royal National Orthopaedic Hospital, Stanmore

$25,000 Model Systems Development Grant - Cell Lines & Xenographs

Dr. Flanagan is a bone pathologist and runs a lab focused on identifying the molecular etiology of bone tumors. She published the first gene expression profile data for chordoma in 2006, and identified that brachyury was uniquely expressed in chordoma. Since then her lab has studied a variety of signaling pathways in chordoma and has performed mutational analysis in several dozen candidate genes. In this project she will establish new chordoma cell lines and xenographs using a variety of methods including telomerase immortalization, tumor cell enrichment, and organotypic culturing.

Adrienne Flanagan

Development and Characterization of Chordoma Xenographs

David Loeb, MD, PhD
Department of Oncology
Johns Hopkins University

$25,000 Model Systems Development Grant - Xenographs

Dr. Loeb is a pediatric medical oncologist and co-director of the Johns Hopkins Sarcoma Center. In collaboration with Dr. Ziya Gokaslan and his colleagues in the Department of Neurosurgery, Dr. Loeb is collecting chordoma tissue from surgeries at Johns Hopkins, and implanting this tissue in immunodeficient mice in an attempt to establish a serially transplantable chordoma xenograph model. He is also characterizing the xenographs on a molecular level to ensure that they faithfully represent the tumors from which they were derived.

David Loeb

Molecular Validation of Chordoma Mouse Xenographs

Elena Tamborini, PhD
Department of Pathology
Istituto dei Tumori Milan

$25,000 Model Systems Development Grant - Xenographs

Dr. Tamborini is a molecular biologist in the lab of Dr. Silvana Pilotti, and is a colleague of Dr. Paolo Casali, who has one of the most active chordoma oncology practices in Europe. This group in Milan has previously implanted chordomas in mice, with limited success. In this project, Dr. Tamborini is performing detailed genetic and biochemical analysis of the implanted tumors and comparing them to the primary tumors from which they were derived. This validation is important because it will indicate whether these xenographs are suitable models of chordoma.

Elena Tamborini

Characterization of Chordoma Cell Lines and Tumors

Michael Kelley, MD
Department of Medicine, Division of Hematology and Oncology
Duke University

$45,000 Research Grant

The Chordoma Foundation is supporting a variety of research projects in Dr. Kelley’s lab by partially funding the salary of research scientist Dr. David Alcorta. This work includes performing genetic and genomic analysis of chordoma, investigating the role of a protein called brachyury in chordoma, studying the PI3K pathway in chordoma, and creating new chordoma cell lines. In addition, Dr. Alcorta is working with the NIH Chemical Genomics Center on a project to screen all FDA approved drugs against chordoma cell lines. He also manages the Chordoma Foundation Cell Line Panel, distributing chordoma cells to researchers across the world.

Michael Kelley