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Tag Archives: Dr. Mick Bhatia

Friday Science Review: February 25, 2011

Fusion Construct Promotes Erythropoietic Development from Human Embryonic Stem Cells

McMaster University ♦ The Ottawa Hospital ♦ British Columbia Cancer Agency

Published in Stem Cells, Feb. 15, 2011

The homeobox (Hox) genes encode a group of highly conserved transcription factors that have been known to regulate hematopoietic differentiation. As a result of their involvement in hematopoietic proliferation and lineage commitment, Hox genes have also been implicated in leukemogenesis. Researchers from Dr. Mick Bhatia’s lab have created a fusion construct that alters the hematopoietic differentiation program of human embryonic stem cells (hESCs). They chose the homeobox gene HOXA10, and partnered this with NUP98, a gene that is often found fused to Hox genes in human leukemias. After introduction of the fusion construct into undifferentiated hESCs or early-stage blood progenitors there was a marked increase in the level of erythroid progenitors founds in culture. Introduction of the construct to later-stage cells already committed to the hematopoietic lineage had no effect on the yield of erythropoietic cells. Apparently, unlike some of the fusion constructs observed in leukemias, the combination of HOXA10 and NUP98 does not lead to malignant expansion. Given the interest Dr. Bhatia and his group have in the production of blood cells, it is foreseeable that this fusion construct could be used in future differentiation protocols to bias the differentiation of hESCs towards the erythropoietic lineage.

Ubiquitination Factor E4B, A Novel Target for Brain Cancer

University of Alberta ♦ Published in Nature Medicine, Feb. 13, 2011

The tumour supressor gene TP53 and its protein product p53 are at the root of many cancers. TP53 is inactivated in 50% of human tumours. The resulting deficiency in p53 allows fledgling cancer cells to circumvent apoptotic programs and proliferate wildly. Deficiency in p53 protein may result from a mutation in the TP53 gene, or as is more frequently the case, inactivation of the p53 protein. Inactivation is often the result of ubiquitination. A specific class of enzymes in the body has the ability to add ubiquitin to proteins which marks them for degradation by other protein machinery. However, the molecular mechanisms behind inactivation of p53 in the brain remain largely understood.  Dr. Roger Leng and his team at the University of Alberta have identified a novel mechanism of inactivation in brain tumours: a ubiquitination factor (UBE4B) that directly interacts with the p53 protein destabilizing it and marking it for destruction. The factor was found to interact with an enzyme (Hdm2) that is also involved in ubiquitination. Silencing UBE4B in xenotransplanted tumours led to impaired tumour growth while over-expression of the factor was associated with amplification of its gene suggestive of a positive feedback mechanism. This discovery elucidates a potential target for treating medulloblastoma and ependymoma, two brain cancer types that exhibit inactivation of the p53 protein.

Stem Cell Breakthrough: Direct Conversion of Human Skin to Blood

A breakthrough in Canadian stem cell research this week, published in Nature, as researchers led by Dr. Mick Bhatia of the Stem Cell and Cancer Research Institute at McMaster University have devised methods to differentiate human skin cells into blood cells. In many differentiation protocols researchers are forced to first reprogram cells to a pluripotent intermediate before differentiating these primitive cells into the desired cell type. The protocol developed by Dr. Bhatia utilizes a ‘trans-differentiation’ process where skin cells are turned directly into blood cells without the need for reprogramming to a primordial state. As a result, the differentiation process is not only simpler, but safer from a therapeutic standpoint. Read more of this post


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