BBS Faculty Member - Alan Cantor

Alan Cantor

Department of Pediatrics

Boston Children's Hospital
Karp Research Building, Rm. 7213
1 Blackfan Circle
Boston, MA 02115
Tel: 617-919-2026
Fax: 617-730-0222
Email: alan.cantor@childrens.harvard.edu
Lab Members: 3 postdoctoral fellows, 1 graduate student, 1 research assistant
Visit my lab page here.



Hematopoiesis serves as a useful model system for studies of cell fate determination and lineage plasticity. Lineage-specific transcription factors play essential roles in these processes by activating terminal maturation genes, while simultaneously repressing alternate lineage and stem cell genes. Yet, how these factors selectively activate some genes while repressing others remains unclear. Importantly, normal hematopoietic transcription factors are also frequently mutated in human leukemias and pre-leukemic conditions. Therefore, further understanding their regulatory mechanisms should provide novel insights into the molecular pathogenesis of these cancers and potentially lead to new therapeutic strategies.

Current emphasis in my lab is on GATA, RUNX and ETS family transcription factors and their association with epigenetic regulators and cell-signaling molecules. We are currently taking a number of approaches to these studies, including: (1) a proteomic strategy involving the isolation and characterization of their associated multiprotein complexes. 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 knockout and knockin techniques; (2) ChIP-seq to identify genome-wide chromatin occupancy sites of these factors and their associated proteins; (3) RNA-seq analysis to examine gene expression changes associated with chromatin occupancy events; (4) gel filtration chromatography and mass spectrometry to identify key post-translational modifications involved in assembly of the transcription factor multiprotein complexes; (5) manipulation of induced pluripotent (iPS) cells from patients with hematopoietic disorders to test mechanistic hypotheses ; and (6) linkage analysis and whole exome sequencing to identify novel genes involved in families with leukemia predisposition.

Key recent findings include identification of physical and functional interactions between GATA and RUNX factors with Polycomb Repressive Complexes; elucidation of a novel regulatory axis for RUNX1 involving src-mediated tyrosine phosphorylation and Shp2 mediated tyrosine dephosphorylation; 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 contribute to a unique form of leukemia found in newborns with Down syndrome.





Last Update: 6/24/2014



Publications

For a complete listing of publications click here.

 


 

Huang H, Yu M, Akie TE, Moran TB, Woo AJ, Tu N, Waldon Z, Lin YY, Steen H, Cantor AB. 2009. Differentiation-dependent Interactions between RUNX-1 and FLI-1 During Megakaryocyte Development, Mol. Cell. Bio. 29:4103-15. PMCID: PMC2715817.

Yu M, Riva L, Xie H, Schindler Y, Moran TB, Cheng Y, Yu D, Hardison R, Weiss MJ, Orkin SH, Bernstein BE, Fraenkel E,
Cantor AB. 2009. Novel Insights into GATA-1 Mediated Gene Activation versus Repression via Genome-wide Chromatin Occupancy Analysis. Molecular Cell, 36: 682-695. [NIHMS:163436] PMCID: 19941827; PMC2800995.

Bai, X, Kim J, Yang Z, Jurynec MJ, Akie TE, Lee J, LeBlanc J, Sessa A, Hong J, DiBiase A, Zhou Y, Grunwald DJ, Lin S,
Cantor AB, Orkin SH, Zon LI. 2010.TIF1γ controls erythroid cell fate by regulating transcription elongation. Cell 142:133-143. PMID: 20603019; PMCID: PMC3072682.

Kim J, Woo AJ, Chu J, Snow J, Fujiwara Y, Kim CG,
Cantor AB; Orkin SH. 2010. Separable core pluripotency, polycomb, and Myc network modules in embryonic stem cells and cancer. Cell, 143:184-6. PMID: 20946988; PMCID: PMC3018841.

Yu M, Mazor T, Huang H, Huang H-T, Kathrein KL, Woo AJ, Chouinard CR, Labadorf A, Akie TE, Moran TB, Xie H, Zacharek S, Taniuchi I, Roeder RG, Kim CF, Zon LI, Fraenkel E,
Cantor AB. 2012. Direct Recruitment of Polycomb Repressive Complex 1 to Chromatin by Core
Binding Transcription Factors.
Molecular Cell, 45:330-343. [NIHMS 349597]. PMIC:22325351; PMC ID: PMC3278717.

Huang H, Woo AJ, Waldon Z, Schindler Y, Moran TB, Zhu HH, Feng G-S, Steen H,
Cantor AB. 2012. A Src Family Kinase-Shp2 Axis Controls RUNX1 Activity in Megakaryocyte and T Lymphocyte Differentiation. Genes Dev 26: 1587-1601.

Woo AJ, Wieland K, Huang H, Akie TE, Piers T, Kim J,
Cantor AB. 2013. Developmental Differences in Interferon Signaling Affect GATA1s Induced Megakaryocyte Hyperproliferation, J Clin Invest. 123:3292-3304.



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