Stephanie Cherqui

Biography

My laboratory focuses on developing stem cell and gene therapy strategies for degenerative multi-systemic disorders, and to understand the cellular and molecular mechanisms by which hematopoietic stem cells can lead to tissue repair in non-hematopoietic genetic diseases.   Although hematopoietic stem and progenitor cell (HSPC) transplants are routinely used to treat hematologic disorders, their potential utility to treat progressive tissue damage is controversial. Using the mouse model of cystinosis, a lysosomal storage disorder, we showed that hematopoietic stem cells could treat this disease whereas cystinosis leads to multi-organ failure and cystinosin, the protein involved, is a lysosomal transmembrane protein. While we are working towards the development of a clinical trial for cystinosis using autologous hematopoietic stem cells and a lentiviral vector strategy, we are also using this model to investigate the cellular and molecular mechanisms of tissue repair by hematopoietic stem cells in the context of non-hematopoietic disorders. The study of the mechanism so far demonstrated that a large subset of HSPCs differentiated into macrophages that can transfer cystinosin-bearing lysosomes to the deficient host cells via long tubular extensions known as tunneling nanotubes (TNTs). Our findings bring new perspectives to regenerative medicine as they should be applicable to other multi-compartment disorders involving deficient intracellular organelles disorders. Thus, because TNTs can transfer not only lysosomes but also other cellular organelles such as mitochondria, we tested HSPC transplantation in the mitochondrial disorder Freidreich’s ataxia for which no treatment is currently available. Using the mouse model, we showed for the first time that transplantation of wildtype HSPC led to the complete rescue of the neurologic and muscular complications of FRDA. We also showed that the underlying mechanism involved the transfer of frataxin from HSC-derived microglia/macrophages to the diseased host cells.

Research Interest

Genetics & Genomics Stem Cell Biology