About the Blau Laboratory

 

We study the mechanisms that control stem cell fate and nuclear reprogramming

 

Approaches used in the Blau laboratory capitalize on four unique approaches to decipher the regulation of cell plasticity:
- Elucidating and mimicking tricks used by newts,
- Using bioengineering to modulate naturally existing stem cells in tissues like muscle,
- Determining the mechanisms of nuclear reprogramming by cell fusion,
- Studying and treating the cardiac and muscle defects in a novel mouse model that mimics Duchenne Muscular Dystrophy.
Mechanistic insights gained from these studies are translated into strategies to regenerate human tissues.


Technologies: Developed and/or employed by the Blau laboratory range from bioluminescence non-invasive imaging, mouse nodels of disease, RNAseq, ChIP seq, bioengineered substrates, nuclear reprogramming in heterokaryons, induced pluripotent cells (iPS), flow cyotmetry - CyTOF, to novel cell tracking algorithms.

 

HISTORICAL PERSPECTIVE

Helen Blau’s research is focused on the regulation of cell fate. In the 1980s her lab challenged and changed the dogma that the mammalian differentiated state was"terminal", i.e., fixed and irreversible. The Blau lab fused cells of two different species in different ratios to form stable non-dividing syncytia (heterokaryons). These experiments demonstrated that by altering the balance of cytoplasmic proteins, programs of gene expression could be changed. For example, the genes characteristic of a muscle cell could be activated in a human liver cell. This body of work was remarkable, as it showed that genes silenced in the course of differentiation and development in humans,could be readily reawakened and expressed. Moreover, these major changes in gene expression occurred in the absence of cell division and DNA replication. These findings surprised the scientific community by showing that in mammals the typically stable state of a differentiated cell (liver does not normally beget muscle) is governed by mechanisms that are continuously active and governed by the balance of proteins present in the cytoplasm at any given time. These discoveries extended the findings and fundamental principles of gene regulation described for the Operon in prokaryotes by Jacob and Monod to higher eukaryotes. Moreover, they now provide the foundation for the diverse approaches to nuclear reprogramming that are the crux of the burgeoning field of stem cell biology and regenerative medicine.

Reviewed in Blau, Trends in Genetics, 1989; Blau and Baltimore, J. Cell Biol. 1991; Blau, Ann. Rev. Biochem.1992; Yamanaka and Blau,Nature, 2010.

Now the Blau laboratory is employing a number of diverse approaches to perturb the balance of regulators and generate new cell sources for use in regenerative medicine.