Current Research Projects

We support research with SMARCB1 scientists we know and trust and with whom we have open, high-quality dialogue. A collaborative spirit and approach are indispensable.

We will provide regular updates on the programs we support and continue to explore other opportunities to help research on SMARCB1-deficient cancers. Don’t hesitate to contact us if you would be interested in working with us on your SMARCB1 project idea! 

Project #1: Deciphering SMARCB1-deficient sinonasal carcinoma (SDSC)

Team leadership: Sophie Postel-Vinay, Gustave Roussy, Paris, France

Anticipated duration: 3-4 years
Committed Funding over 36 months: €150,000
Budget 2024: €40,000

Productive research begins with building a collection of biological samples and then building the experimental tools needed to test hypotheses. SDSC has only recently been understood to be a separate entity in the sino-nasal undifferentiated carcinoma (SNUC) world. While SNUC is well known to Head & Neck oncologists, many are not aware of SDSC, and do not test for it consistently, meaning its prevalence is not known. Leveraging on the Gustave Roussy biobank and patient files, this program aims to re-test GR’s existing collection of tumor samples for SMARCB1 inactivation, and, in the longer term, to build a clinical classification and develop in-house patient-derived disease models (organoids, PDX, cell lines).

Sophie Postel-Vinay (MD, Ph.D), is Physician Scientist at the Drug Development Department at the Gustave Roussy Institute in Paris, where she is Senior Medical Oncologist and Group Leader of U981 INSERM research unit focusing on chromatin remodeling, DNA repair and Epignetics. Sophie was awarded the Irène Joliot Curie prize of the French Academy of Sciences and the Gallet et Breton Prize of the French Medicine Academy for her past research.

SMARCB1 Hope has committed a total of €150,000 of funding over 36 months, covering part of the cost of an engineer and a pathologist dedicated to the program, as well as that of molecular profiling of the samples in the study, starting March 2024.

Project #2: Development of TCR-T cells for the treatment of SMARCB1-deficient tumors exploring ERVs as a novel source of tumor-specific antigens

Team leadership: Eliane Piaggio, Franck Bourdeaut and Josh Waterfall, Institut Curie, Paris, France

Anticipated duration: 2 Years
Committed Funding over 24 months: €140,000
Budget 2024: €50,000

Targeted therapy is a type of cancer treatment that uses drugs to target and kill cancer cells without affecting normal healthy cells. To develop a targeted treatment, you first must identify tumor-specific antigens ("TSAs") which are proteins expressed only on cancer cells and not normal cells.

Working with rhabdoid tumors, the most frequent malignancies within the SMARCB1-deficient cancer family, this team recently discovered that SMARCB1 loss-of-function in these tumors induces the re-expression of endogenous retroviruses (ERVs) in tumoral cells, in turn activating the immune system’s T-cells to fight these “intruders.” The ERVs are former viruses which have been incorporated in the non-coding part of the DNA at some point in Evolution. The exact nature of the rhabdoid tumor TSAs that are recognized by T-cells remains unknown.

Using SMARCB1-deficient tumor samples matched with healthy cells from the same patients, this program aims to help identify immunogenic epitopes (part of TSAs recognized by the immune system) in SMARCB1-cancers that could be further exploited to design novel, more effective and less invasive immunotherapies for patients. It has the potential to open new therapeutic avenues for other cancers that share similar low mutation burden (such as medulloblastoma, neuroblastoma,…) or are driven by inactivation of other genes in the SWI/SNF chromatin remodeling complex.

Eliane Piaggio trained as a clinical biologist and immunologist at the National University of Rosario in Argentina and completed her post-doctoral studies in France. Eliane directs the Translational Immunotherapy Team at Institut Curie with a primary focus on T-cell-based immunotherapy for cancer and infectious and autoimmune diseases. She is co-founder of Egle-Therapeutics, a biotech developing Treg-based immunotherapies.

Franck Bourdeaut is a researcher-clinician pediatric oncologist at Institut Curie. His two main fields of clinical practice are pediatric neuro-oncology and genetic predisposition to childhood cancer. As part of the Translational Research in Pediatric Oncology Lab directed by Dr Olivier Delattre, Franck heads a research team dedicated to SMARCB1-deficiency in cancer, focusing on combining immunotherapy and epidrugs to develop innovative therapies for rhabdoid tumors and other SMARCB1-deficient cancers.

Joshua Waterfall trained in the US and is a tenured researcher with Inserm and group leader of the “Integrative Functional Genomics of Cancer” lab at Institut Curie. His lab focuses primarily on how transcriptional dysregulation in cancer cells generates tumor specific antigens and on mapping the gene regulatory networks driving anti-tumor T cell responses. His team takes a multi-disciplinary approach, combining artificial intelligence and computational algorithm development, high-throughput proteogenomic profiling technologies, and access to clinical samples from cancer patients.

SMARCB1 Hope has committed a total of €140,000 of funding over 24 months to cover the annual salary of the post-doc researcher in charge of coordinating the program, starting in April 2024.