Greetings! My first post here will be a brief introduction. More in-depth experiment and data posts are coming soon!
I am a post-doctoral research associate in the UNC Catalyst for Rare Diseases1. Throughout my education and training, I have been interested in cancer – I worked on epigenetics of ovarian cancer as an undergraduate and then mechanisms of cell invasion (in a developmental biology system) as a Ph.D. student. Now as a post-doc with the UNC Catalyst for Rare Diseases, my interest in cancer continues in the form of a project on chordoma, a rare bone cancer.
At the recent International Chordoma Research Workshop, the idea of sharing data, reagents, and research progress was raised. Given the affiliation of the UNC Catalyst for Rare Diseases with the open-science SGC, our group seemed like optimal candidates to initiate this undertaking. Other chordoma researchers: I welcome you to join us! Open science will accelerate the pace of research!
Chordoma is a rare cancer that occurs along the bones of the central nervous system – from the base of the skull to the tip of the spine. Chordomas arise from remnants of the notochord – a developmental precursor to the vertebral column – and thus are almost always driven by expression of the notochord transcription factor Brachyury (encoded by the gene T). Therapeutic avenues for chordoma are tricky because they are rare (roughly 1 in 106 people), slow-growing, and often difficult to resect because of proximity to vital and sensitive structures. Current standard of care is surgical resection followed by radiation, but recurrence, metastasis, and mortality still happens in many cases despite these best practices.
Thus, improved knowledge of the biology of chordoma and the development of new therapeutics are vital for bettering the lives of patients with this rare bone cancer. I have two primary interests in Chordoma which will appear frequently in this blog:
- Brachyury – this embryonic transcription factor of the notochord is encoded by the gene T. But T is going to give you way too many Google search results, so most always we’ll stick with Brachyury. This transcription factor is also overexpressed in some other cancers, though its role as a driver in these instances is unclear. While some of the biology of this transcription factor is known – including some of the genes it may regulate – much remains to be learned, including potential chaperones and binding partners. Brachyury presents an intriguing therapeutic avenue for this cancer because of its ubiquitous expression.
- EGFR – this receptor tyrosine kinase is overexpressed (but not mutated) in many chordomas and its ligand, EGF, is a direct transcriptional target of Brachyury. EGFR inhibitors are a potential therapeutic for chordoma, and in collaboration with SGC-UNC, we are working on new inhibitors of EGFR and other kinases as potential chemotherapeutics for chordoma (more information: https://www.chordomafoundation.org/targets/egfr/)
With this background out of the way, a backlog of data will be forthcoming.
My work owes many thanks to the Chordoma Foundation for their inspiring array of reagents and data. They are a superb example of how a patient advocacy/disease awareness foundation should be run and how the sharing of reagents and insights can accelerate the progress of research and therapeutic development.
If you are unfamiliar with chordoma, suggested references include the following:
Chordoma Foundation – Understanding Chordoma
Chordoma Overview (Lancet, 2015)
Role of Brachyury in Chordoma; Presnet et al (2010) J Pathology
The Brachyury Functional Network; Nelson et al (2012) J Pathology
EGFR and EGFR inhibitors in chordoma; Scheipl et al (2016) J Pathology
1The UNC Catalyst for Rare Diseases: We are a biology group started by the SGC (Structural Genomics Consortium) at the University of North Carolina through funding from the Eshelman Institute for Innovation (in the UNC Eshelman School of Pharmacy). Our commitment and objective is to be a research group that can be a resource for patients and other researchers, a hub with wet lab expertise to do be a source of knowledge in rare diseases. As an “SGC spin-off”, as I like to call our lab, we are committed to a practice of open science. You can follow us on Twitter here!