Alan B. Cantor


Department of Pediatrics
Children's Hospital
Karp Research Building, Room 07213
1 Blackfan Circle
Boston, MA 02115
Tel: (617) 919-2026
Fax: (617) 730-0222
Email: alan.cantor@childrens.harvard.edu

Web Page: The Cantor Lab Page
2 postdoctoral fellows, 1 graduate student, 1 research assistant


The hematopoietic system serves as a useful model for studies of cell fate determination and lineage plasticity.  Lineage-specific transcription factors play essential roles in this process by activating certain genes, while simultaneously repressing alternate lineage genes.  Yet, how these transcription factors carry out their distinct gene-context dependent activities remains unclear.  Importantly, transcription factors involved in normal hematopoiesis are also frequently mutated in human leukemia and pre-leukemic conditions.  Therefore, further understanding the dysregulation of these transcription factors should provide novel insights into the molecular pathogenesis of these cancers, and potentially new therapeutic strategies.  

 

Current emphasis in my lab is on GATA, RUNX and ETS family transcription factors in hematopoietic stem cell biology and differentiation.  We are currently taking four approaches to further understand the regulatory mechanisms involving these factors:  (1) a proteomic strategy involving the isolation and characterization of multiprotein complexes involving these factors.  This utilizes metabolic biotin tagging and streptavidin affinity purification followed by whole lane mass spectrometry.  The functional significance of validated proteins is then assessed by lentiviral shRNA gene silencing in primary cells, zebrafish morpholino experiments, and/or conventional mouse genetic techniques;  (2) ChIP-seq to identify genome-wide chromatin sites occupied by these factors and their associated proteins.  Gene expression studies using cDNA microarray and/or RNA-seq analysis after lentiviral shRNA mediated gene knock down and overexpression of the factor is then performed to relate chromatin occupancy with functional gene and non-coding RNA regulatory events.  (3) gel filtration chromatography and mass spectrometry to identify key post-translational modifications involved in assembly of the multiprotein complexes; and (4) human genetic studies to identify novel genes involved in families with autosomal dominant thrombocytopenia (low platelet counts) and predisposition to leukemia.

  

Key recent findings include identification of physical and functional interactions between GATA and RUNX factors with Polycomb Repressive Complexes (PRC); identification of a key dephosphorylation event that regulates interactions between RUNX and ETS family members in a cell differentiation-dependent manner; identification of the Kruppel-type zinc finger transcription factor ZBP-89 as a novel GATA associated protein that plays a role in erythroid development and human globin gene regulation; and identification of key developmental differences between fetal and adult megakaryocytes that may contribute to a unique form of leukemia found in newborns with Down syndrome.

 

 

 

References:

 

For a complete listing of publications on PubMed, click here.

 

BBS webpage updated 5/25/2010