Funded Research Projects

Sarcoma Research Project at Cold Spring Harbor Laboratory

Dr. Chris Vakoc's research team at CSHL has grown, with three expert researchers now exploring the causes and potential treatments for Rhabdomyosarcoma (RMS). Our daughter, Daniela passed away from this rare cancer, which is what led us to take an active role in finding a cure. They are the number one academic institution in the world for producing high-quality scientific research.  We are proud to support the work of Dr. Chris Vakoc and his team. His team's work is soley focused on Rhabdomyosarcoma and researching the genetic underpinnings of Rhabdomyosarcoma and the search for a possible drug target. 


Using a CRISPR-based screen that can report whenever a gene loss allows rhabdo cells to myodifferentiate, CSHL has identified strategies for changing rhabdo cells in normal muscle.  In addition, they have discovered several targets in Ewing’s Sarcoma, Rhabdomyosarcoma, and Synovial Sarcoma.

Going forward, the lab will be working to understand the mechanism by which loss of either of those genes leads to differentiation and preliminary data hints that it might be related to the fusion oncoprotein.

Haystack II Project for Embryonal Rhabdomyosarcoma at cc-TDI

The Daniela Conte Foundation has partnered on this flagship project with the Children's Cancer Therapy Development Institute (cc-TDI).

Soft tissue sarcomas are among the top 5 causes of death from childhood cancer.  Until now, rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) have had less than 40% survival when full surgical removal is not possible, when the cancer has spread or when the tumor becomes resistant to drugs. To address this pressing & unmet clinical need, we are utilizing multiple-genetically engineered mouse (GEM) models of alveolar and embryonal subtypes of RMS and the undifferentiated pleomorphic sarcoma (UPS) subtype of NRSTS created by the Keller laboratory cc-TDI.  Development of these GEM models has already resulted in the understanding of both underlying biology and treatment approaches to RMS.  


Now, through the cc-TDI and Novartis partnership, we have access to results from a completed screen of 640,000 compounds across a range of cell origins and mutation combinations for tumor cultures taken from mouse sarcomas.  A total of 446 "hits" across tumors of differing cells of origin and sarcoma subtypes were identified.  These hit compounds are from wholly unexpected compound classes.  To bring these new chemical classes to clinical investigation in rhabdomyosarcoma, we will carefully study the top hit and how this FDA-approved cardiovascular drug class works for rhabdomyosarcoma.  With this understanding, we can optimize an even better drug that does not change blood pressure but can effectively treat embryonal and alveolar rhabdomyosarcoma.  We hope that this example of de-risking drug development will break through a 48 year unmet need for effective new RMS treatments.