The broad interest of the Shimamura lab is the genetic and molecular mechanisms regulating hematopoiesis and clonal evolution to MDS and leukemia.  The Shimamura lab studies inherited bone marrow failure syndromes and myelodysplastic syndromes, which are characterized by impaired blood cell production and leukemia predisposition.  The lab studies primary and immortalized patient-derived cells and has developed cellular models of marrow failure and MDS.  Genetic and genomic studies of marrow failure and MDS are ongoing.

akiko-iiOur work has identified novel genes causing bone marrow failure, MDS, and cancer predisposition.  It is increasingly recognized that germline genetic variants contribute to bone marrow failure, MDS, and leukemia in a significant subset of pediatric and young adult patients.  Genetic studies of familial marrow failure and familial MDS/leukemias are ongoing.  We have established a repository of clinically annotated blood and marrow samples for these studies.  The molecular functions of novel genes in hematopoiesis and leukemogenesis are under investigation.  The effects of identified variants on gene function are also studied.

We are particularly interested in ribosomal disorders causing marrow failure and leukemia.  How disorders of the ribosome, an essential cellular organelle, result in such tissue-specific phenotypes remains a fascinating and critical question.  Shwachman Diamond syndrome (SDS) is an autosomal recessive disorder characterized by bone marrow failure and leukemia predisposition.  Mutations in the SBDS gene are found in around 90% of cases of SDS but a subset of patients remain genetically undefined.  We are conducting translational studies to understand how SBDS mutations result in hematopoietic failure and promote clonal evolution to MDS and AML.  To understand the clinical complications and molecular pathogenesis of SDS, an SDS Registry was organized together with collaborators at Cincinnati Children’s Hospital for the collection of clinical data and annotated biological samples for clinical and  laboratory investigation (  The goal of these studies is to improve diagnosis, inform medical management, and develop more effective treatments with less toxicity.

Current Lab Projects

1. Genetic and molecular pathogenesis of bone marrow failure, MDS, and leukemia predisposition

These projects involve whole exome and whole genome sequencing to identify causative genes for bone marrow failure, MDS, and leukemia predisposition.  Gene variants are queried using genetic, molecular, biochemical, and cell biology approaches to understand the molecular functions of novel genes in hematopoiesis and clonal evolution.  Effects on cell survival, proliferation, and hematopoiesis are also queried.

2. Modeling marrow failure and MDS using induced pluripotent stem cells

We have derived induced pluripotent stem cells (iPSC) from patients with bone marrow failure syndromes and genomically engineered mutations to model MDS (in collaboration with Dr. Eirini Papapetrou, Mount Sinai).  The molecular and cellular consequences of MDS-associated mutations in the context of marrow failure are under investigation.

3. High-throughput screening using small molecule compounds and functional genomics to identify novel therapeutic targets for bone marrow failure and MDS.

We are using patient-derived iPSC as a platform for high-thoughput screening to identify promising small molecules or target genes to treat bone marrow failure and MDS/leukemia.






Laboratory techniques used by the lab include: 

  •             Protein biochemistry
  •             Molecular biology
  •             Genomic sequencing and analysis
  •             Immunofluorescence microscopy
  •             Flow cytometry
  •             Hematopoiesis assays using primary human CD34+ cells or human induced pluripotent stem cells
  •             Lentiviral transduction to introduce cDNAs or knockdown gene expression
  •             High throughput screens using small molecule compounds or functional genomics
  •             Establishment of primary patient-derived cell cultures

 Clinical research

Dr. Shimamura leads several clinical and translational research studies in bone marrow failure.  She directs the North American Shwachman Diamond Syndrome Registry (SDSR) together with Dr. Kasiani Myers and Dr. Stella Davies at Cincinnati Children’s Hospital.  The SDSR ( collects clinical data and biological samples to investigate the clinical complications and molecular and genetic causes of SDS with the goal of improving diagnosis, medical management, and treatment.  Dr. Shimamura also serves on the Executive Committee of the North American Pediatric Aplastic Anemia Consortium (NAPAAC) which is comprised of over 26 pediatric hematology centers across the country working together to improve the diagnosis, treatment, and outcomes of pediatric aplastic anemia.  She also works closely with colleagues in the hematopoietic stem cell transplant program to improve transplant outcomes for pediatric bone marrow failure and MDS.