Robert Blelloch, M.D., Ph.D.
	Epigenetics, Stem Cells, and Cancer
	Email: BlellochR@stemcell.ucsf.edu Websites:
Selected Publications | Complete Publications

Stem cells exist both in the developing embryo and in many organs of the adult. Differentiation of stem cells is tightly regulated so that as they become increasingly specialized, they lose the potential to revert or transform into other cell types. This regulation is very important both to maintain organ function and to avoid the possibility of uncontrolled cell growth, the basis of cancer. Very little is known about the mechanisms that control and lock-in cell differentiation. We now know that under exceptional circumstances, it is possible to reverse a fully differentiated adult cell into early embryonic stem cell. This amazing feat is the result of somatic cell nuclear transfer where a differentiated nucleus is transferred into an female egg. The egg is then able to reprogram the differentiated nucleus into an embryonic nucleus that is then able to direct development of an entirely new organism.

Our laboratory is interested in determining the molecular mechanisms that regulate stem cell differentiation and de-differentiation and how these mechanisms become deregulated in cancer. In particular, we are interested in epigenetic mechanisms that globally regulate cell fate choice by controlling large swaths of the transcriptome and proteome. These mechanisms include DNA methylation, histone modifications, and the emerging field of non-coding RNAs. Using somatic cell nuclear transfer, we have shown critical roles for these mechanisms in maintaining both normal differentiated as well as abnormal tumorigenic cell fates. Furthermore, using mouse genetics, we have recently shown an essential role for a subclass of non-coding RNAs, microRNAs, in stem cell differentiation.

We continue to pursue these exciting findings in both the mouse and human systems. We are using genetic and biochemical methods to evaluate the role of epigenetics in embryonic and somatic stem cells and cancer. (1) We are studying the role of methylation and cellular context in tumor development. (2) We are following up our microRNA findings by identifying specific microRNA regulated pathways required for stem cell self-renewal and early differentiation. (3) We are identifying and evaluating the role of other classes of non-coding RNAs in stem cell function. (4) We are determining mechanistic links between the various types of epigenetic modifications. Together this work should lead to a deeper understanding of the role of epigenetics in development and disease.

Selected Publications

Wang Y, Medvid R, Melton C, Jaenisch R, Blelloch R. DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet. 2007: 39: 380-5. Epub 2007 Jan 28.

Blelloch, R., Wang, Z., Meissner, A., Pollard, S., Smith, A., and Jaenisch, R. Reprogramming efficiency following somatic cell nuclear transfer is influenced by the differentiation and methylation state of the donor nucleus. Stem Cells 2006: 24: 2007-2013.

Blelloch R.* , Hochedlinger K.*, Yamado Y., Brennan C., Mintz B., Chin L., Jaenisch R. Nuclear Cloning of Embryonal Carcinoma Cells. PNAS 2004: 101: 13985-90**.

Hochedlinger K.*, Blelloch R .*, Brennan C., Yamado Y., Kim, M., Chin L., Jaenisch R. Reprogramming of a Melanoma Genome by Nuclear Transplantation. Genes and Development 2004: 18: 1875-1885**.

*Authors Contributed Equally
** Papers highlighted in Science (Editor's Choice) and Nature Medicine

Information last updated April 2007