From the Founder, Dr. Eszter Hars
Dear SDS community,
I am so excited to have been able to launch this project. To recap: This project is the first major puzzle piece in our strategy to drive therapy development for SDS. Our strategy includes developing key research tools for the research community by partnering with the best experts in the field. Therapy development is a very complex and expensive endeavor, and we (as a rare disease community) need to be very strategic and focused in order to make progress, fast. We are celebrating the opportunity to make this transformational impact on research and do our part for a brighter future for our children and patients.
We recently hosted a webinar to discuss this project with this expert panel, and compiled a short video of the highlights.
This mouse model project is filling a huge need: The research community needs a mouse model that (a) is based on the SBDS mutation that is most prevalent in the patient population (the 258+2T>C splice-site mutation), and (b) is able to recreate SDS symptoms representative of SDS in patients. The benefits include:
having both the typical genetic and protein defect expressed in all cells of a mammalian model, so that interactions between different cells and tissues can be measured.
having a viable mouse, so important long term phenotypes (such as clonal evolution, leukemia, immune defects, cognitive challenges) and potential benefits of therapies can be measured.
enabling the development of gene targeted therapies, including gene editing, base editing, and antisense oligonucleotide therapies (ASOs).
This is exactly what we set out to do in partnership with the Jackson Laboratory and leading SDS scientists, including Dr. Johanna Rommens (SickKids Research Institute/Toronto, Canada), Dr. Marc Raaijmakers (Erasmus MC Cancer Institute, The Netherlands), and Dr. Alan Warren (Cambridge University Hospitals, UK).
About the SDS experts and scientists on the webinar panel:
Senior Scientist Emeritus at SickKids Research Institute/Toronto, Canada
Dr. Rommens is a Senior Scientist Emeritus at SickKids Research Institute and a Professor in the Department of Molecular Genetics at the University of Toronto. She and her team have identified the main gene responsible for cystic fibrosis, and in 2003, the main gene responsible for Shwachman-Diamond Syndrome (SDS), the SBDS gene. With this discovery, she is a true pioneer and has put SDS on the biomedical research map. She proceeded to develop multiple mouse models for SDS, enabling a wide range of scientific insights into the disease. Her input into the current mouse project has been instrumental.
Professor of Haematology, Cambridge University Hospitals, UK NHS Foundation Trust
Professor Warren is currently Professor of Haematology at the University of Cambridge, UK, Clinical Lead for Bone Marrow Failure and Myelodysplastic Syndromes at Cambridge University Hospitals, and elected Fellow of the Academy of Medical Sciences in 2005.
His lab is focused on ribosome biology and the clinical impact of its defects. Ribosomes are the universally conserved macromolecular machines that decode the mRNA to make proteins. Defects in the ribosome assembly process cause the 'ribosomopathies', a fascinating new group of human developmental disorders that perturb hematopoietic stem cell function and promote progression to bone marrow failure, myelodysplastic syndrome and acute leukaemia. Professor Warren's lab discovered that defective assembly of ribosomes, the machines in all our cells that make protein, causes Shwachman-Diamond syndrome. Currently, he is developing a compound screening program based on a drosophila SDS model to find drug candidates for SDS, and if successful, will need mouse models to move the development forward,
Professor of Hematology, Erasmus MC Cancer Institute, the Netherlands
Prof. Dr. Marc H.G.P. Raaijmakers, MD, Ph.D. is a professor of Hematology in the Department of Hematology at the Erasmus MC Cancer Institute, Rotterdam, the Netherlands. He completed postdoctoral research at the Department of Stem Cell and Regenerative Biology at Harvard University and the Harvard Stem Cell Institute, revealing a concept of niche-induced oncogenesis in the hematopoietic system. He (co)-authored papers in leading journals including Nature, Cell, Cell Stem Cell, J. Exp. Med, Blood and Leukemia, served in the editorial boards and provided numerous invited lectures at international meetings, including the European and national societies of Hematology (U.S.A., France, Germany, Spain and Japan) as well as multiple sessions of the International Shwachman-Diamond Syndrome Congress.He chairs the expertise center on Leukemia Predisposition Syndromes at the Erasmus MC Canncer institute and the EHA scientific working group on Rare Hematological Blood Cancers. His laboratory studies micro-environmental contributions to the pathogenesis of hematopoietic disease with an emphasis on the initiation and evolution of preleukemic disorders. He published several articles on Shwachman-Diamond Syndrome and lead the efforts for the development of several SDS research models. His clinical focus is in bone marrow failure syndromes and acute myeloid leukemia.
Senior Director, Mouse Repository & In Vivo Pharmacology Genetic Resource Science / Senior Research Scientist, ME, USA
Dr. Lutz is Director of the Mouse Repository and the Rare and Orphan Disease Center at The Jackson Laboratory. She has fiscal and managerial oversight of a growing collection of more than 8,500 unique strains, including over 1,700 live colonies for distribution to the scientific community. As part of the Mouse Repository program, Dr. Lutz is the Principal investigator on a number of NIH sponsored resource grants, including the Mutant Mouse Regional and Research Center at JAX, The SMSR grant to support recombinant inbred and Chromosome substitution panels, as well as the NICHD Cytogenetic Resource to support Down Syndrome related strains and research. Dr. Lutz also serves as the Director of In Vivo Pharmacology and Efficacy Testing Program in Bar Harbor, which interfaces with biotechnology and pharmaceutical companies to pursue novel therapeutics across a variety of therapeutic areas. She has been awarded a Rare Impact Award from the National Organization for Rare Disorders (NORD) in 2021.
As highlighted in our original project announcement, we are raising funds for the characterization work. To donate or fundraise toward this project, please visit our donation platform or use Facebook fundraiser.