M. William Lensch, PhD

M. William Lensch, PhD

Harvard University Department of Stem Cell and Regenerative Biology
M. William Lensch, PhD

I want to know where blood comes from. Biologically, the blood (hematopoietic) system is fantastically intricate. The complexity of how it's regulated and responds to environmental stresses is on par with any other tissue or organ. All the parts of the body work together in a delicately balanced system of life. However, blood is among a select few parts of the body with additional, symbolic meaning. It is blood that is seen to carry our passions. It is blood that is used to identify our descendants (eg. our bloodline). It is blood that marks those among us with whom we enter into sacred kinship (eg. blood brothers). Literature contains abundant references to blood as a vehicle for understanding deeper human significance. As Sitwell said, "Blood is that fragile scarlet tree we carry with us." Works like Macbeth, The Blank Page (Karen von Blixen), and of course Dracula are just a few examples of how human kind sees blood as something more than cells and plasma pulsing through our vessels. Blood's metaphorical nature alone is worthy of study.

That said, blood is clearly more than poetically significant. People have studied the blood, both healthy and otherwise, for centuries. From Paracelsus' comments on splenomegally in the 1500's to the famous clotting disease of the Romanovs in Russia (and other royal households), what blood does, and how it does it, is of great scientific and medical interest. My background is in genetics and my particular research tries to understand what genes are involved in blood cell production, how that happens at the earliest stages when the first blood cell is made from its non-blood precursor, and how the entire process goes astray in disease. I do this work using human pluripotent stem cells of many types.

The specific use of pluripotent stem cells is key to my work for at least two reasons: (1) I am interested in understanding the pathophysiology of human genetic diseases of the blood and (2) pluripotent stem cells are capable of making any type of cell in our bodies, but have yet to do it; they are a blank slate. Adult blood stem cells are eventually made in nature from a cell like a pluripotent stem cell and I want to understand how that works. The incredible developmental plasticity of pluripotent stem cells makes them perfect platforms for studying how one cell (the fertilized egg) is able to divide and make all of the hundreds of different types of cells in our bodies. This is the central question of developmental biology.

Also, I have a growing interest in germ cell-related tumors including teratomas, teratocarcinomas, and similar masses as these naturally-occuring entities originate from pluripotent cells. Study of similar masses capable of generation in vitro using human pluripotent stem cells will no doubt improve our understanding of these tumors in vivo. Additionally, defining ways to best identify and eradicate tumor-forming cells will be an important milestone as regenerative medicine using materials engineered from human pluripotent stem cells advance towards clinical use.

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