International Research

International Research

Our previous research pages have mostly focused on the main research initiatives that the EHERCC is directly involved in, be that through funding, provisions of data or assisting with patient engagement where necessary, such as a clinical trial. However, the previous pages do not represent the only EHE research taking place – far from it. On this page we provide a summary of other important EHE research that is being supported by our sisters foundations.

The Rubin Lab – Cleveland Clinic, Ohio
Dr B Rubin and his team

Leader Brian Rubin, MD, PhD; Robert J. Tomsich Pathology and Laboratory Medicine Institute, Department of Cancer Biology, Lerner Research Institute, Taussig Cancer Center – Cleveland Clinic Foundation

Key EHE Team Ajaybabu Pobbati, PhD (Project Scientist), Caleb Seavy, MD, PhD (Research Fellow)

Key areas of focus:

  • Identified the disease-defining gene fusion in EHE WWTR1 (TAZ) – CAMTA1
  • Developed an extremely robust Genetically Engineered Mouse (GEM) EHE model
  • Secured major grant awarded to use GEM to study roles in EHE progression
  • Completed pre-clinical research leading to EHE-specific clinical trial of mekinist (Trametinib)
  • Significant investments and progress in drug development and screening
  • Extensive collaboration in basic and translational research
  • In the late stages of developing a YAP1-TFE3 GEM EHE model
  • Repurposing an FDA-approved Drug for EHE Treatment – Pobbati
  • IAG933 Phase I Clinical Trial – Dr. Dale Shepard
International Center of Expertise in EHE – Memorial Sloan Kettering, New York
Dr W Tapp and Dr C Antonescu

Leaders : Dr. Cristina Antonescu (Pathology) & Dr. William Tap (Medical Oncology/Sarcoma)

Key EHE Team :  Evan Rosenbaum, MD (Clinical Fellow), Fabio Vanoli, PhD (Research Associate)

Key areas of focus :
  • Instituted a focused multidisciplinary EHE team
  • Established MSK-EHE tumor bank to enable further studies & model development
  • Investigate secondary genetic abnormalities
  • Characterize the tumor microenvironment and immune infiltrates in EHE subsets
  • Design CRISPR-Cas9 cell culture models of TAZ–CAMTA1 and YAP-TFE3 fusions – study causes of EHE; drug screening
  • Profile clinical and molecular EHE subsets – identify potential new vulnerabilities and therapeutic targets
Lamar Lab – Albany Medical Center, New York
Dr Lamar and his team

Leader :  John Lamar, PhD | Associate Professor, Molecular and Cellular Physiology – Albany Medical Center

Key EHE Team :  Ryan Kanai, PhD Student

Key areas of focus :

  • Identification of TAZ-CAMTA1 Regulators (2019)
    • Several proteins identified
    • Identify mechanisms of regulation and therapeutic pathways to exploit
  • TC Regulation by the Calcium Sensor Calmodulin (2021)
    • Test if activation of CaM represses TC-dependent oncogenic activity
    • Determine the mechanism of CaM regulation of TC
    • Investigate the role of CaM in EHE
  • Identify Druggable Pathways to Treat EHE (2022)
    • Establish a model system in mice to test therapeutic compounds
    • Develop in vivo assays and use to test therapeutic targets
Multi-pronged Canadian Research in EHE (PRO CARE)
Dr A Razak and Dr C Allen

Co-Leaders:  Dr. Albiruni Abdul Razak (Clinical PI), Dr. Christine Allen (Scientific PI) – Princess Margaret Cancer Center

Collaborators :  Dr. Silvia Stacchiotti, Dr. Nadia Zaffaroni – INT, Prof. Robin Jones – RMH, Dr. Paul Huang – ICR

Key areas of focus :

Prong 1

  • Aim 1: Pan-Canadian EHE data curation with virtual tumor biobank
  • Aim 2: Commitment to multi-institutional collaborations to enable EHE data curation and investigation

Prong 2

  • Aim 1: Creation of clinically annotated EHE PDX models
  • Aim 2: Pre-clinical evaluation of mTOR  inhibitors using thermosensitive liposome delivery platform
Australian-US-Canadian EHE Collaboration
Prof K Harvey, Dr M Tanas, Dr A-C Gingras

Co-Leaders : Prof Kieran Harvey,  Peter MacCallum Cancer Centre, Melbourne Australia

Dr Munir Tanas, University of Iowa, Iowa City, USA
Dr Anne-Claude Gingras, Mount Sinai Hospital, Toronto, Canada

Key areas of focus :

  • To understand how the TAZ-CAMTA1 and YAP-TFE3 fusion proteins are affecting the hippo pathway and driving tumour formation
  • To understand how interactors and cooperating complexes regulate transcriptional programs in sarcoma such as EHE
  • Using the results of 1 and 2 to identify and evaluate new therapeutic targets
  • Delivering greater understanding of EHE, new therapeutic targets and disease stabilisation
  • Generously funded by a single Canadian donor