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NYSCF-Druckenmiler Fellow, Dr. Daylon James, had his research on endothelial differentiation and expansion published in Nature Biotechnology on January 17th. In this interview, Dr. James talks about his new work and his life as a stem cell researcher.
Did any experiences in your childhood shape your interest in science and medicine?
One of the first books I read as a kid was “Dawn”, by Octavia Butler.
It was a fantastic imagining of a future in which an alien race could
splice genes on the fly and modify their fitness to new environments
within a generation. The descriptions of these aliens “feeling” the
genome and cutting and pasting sequence was so vivid, it still gives me
a shiver. After reading that book (I was ten), I responded to the
periodic “what do you want to be when you grow up?” with “genetic
engineer.”
How did you end up becoming a scientist? Did you always want to be a researcher?
I think I, like many young people, imagined what I would be in the
finished form, with little attention to the training it would take to
fill that mold. I have long wanted to be a scientist, and the becoming
has involved many defining experiences that are shared among
post-doctoral researchers. But long before I got the degree, “wanting
to become a scientist” was supplanted by “wanting to solve the
problem.” An ironic twist of “wanting” anything is that we rarely lack
for further reaches. I think the reward of a career in stem cell
biology is the satisfaction of addressing so great a problem as human
disease with such an elegant and wide-ranging approach as cell-based
therapy. Although I could not have imagined the reality of my career as
a child, I believe that I always wanted then to enjoy my work as I do
now.
What disease are you specifically working on and how did you choose that disease?
My focus is the creation of endothelial cells (cells that make up blood
vessels) for treatment of vascular disease. Cardiovascular disease is
the leading cause of death in the developed world, and diabetes has
become an unfortunate byproduct of modern lifestyle, posing a severe
health threat. These are ultimately diseases of the vascular system,
and providing an inexhaustible source of endothelial cells could
provide of means of restoring blood supply to dead or dying tissues
that coincide with disease. More fundamentally, blood flow is a
pre-requisite for generation of viable three-dimensional tissue, and as
such, endothelial cells may be an essential adjuvant to therapeutic
grafts of organ specific cells.
How many hours per week do you spend at the lab? Can you describe how
you spend your time professionally? How is your time distributed over
research, teaching, committee work, lecturing or presenting, and
traveling?
An unexpected benefit of working with embryonic stem cells is that it
has been perfect training for becoming a father (my son was born this
past fall). I have often remarked that taking care of my cells is like
having a baby: you have to attend to them everyday and you can’t just
take weekends off. Incidentally, I have recently come to understand
that my analogy drastically underestimated the challenges of
parenthood. Nevertheless, stem cell research demands considerable time
and routine, but more than those things, good science demands focused
attention. The hours spent in the lab are modest (50-60/week), but the
time spent “at work” is more, for it is my privilege and pleasure to
take my work everywhere I go, even if it is only in mind.
What qualities do you think distinguish scientists from other professions (lawyers, doctors, academics, etc)?
I would say imagination, but I think that the most forward thinking in
any profession are endowed with a rich imagination, and I have known
scientists who seemed completely devoid of it. Indeed, it has become
increasingly difficult to find the archetypal stereotype of the
research scientist. I think this is a positive development, as it
reflects a shift in our cultural perception of scientists from solitary
figures with esoteric knowledge, to central players in defining,
communicating and solving the problems that face our people and our
world.
What is your new paper about?
There are many fundamental obstacles confronting the effective clinical
trial of vascular therapies in humans. First, we need a source of
pluripotent stem cells that is safe and matched to the patients’ immune
system. With advances in induced pluripotent technology (some made by
our own NYSCF Fellows), we have made rapid progress toward overcoming
these obstacles. In parallel to these studies, we , and endothelial
cells generated from hESCs, to date, have not been suited for clinical
application. In our study, we have defined conditions for
differentiation and expansion of plentiful endothelial cells that are
appropriate for therapeutic use. To do this, we created a hESC
“reporter” line, in which cells expressed a fluorescent molecule once
they differentiated to endothelial identity. Using this reporter, we
were able to monitor the emergence of endothelial cells in live
cultures, and screen for small bioactive molecules that increased their
yield. By these methods, we isolated a compound that robustly increased
the amount of endothelial cells and defined this compound’s mechanism
of action.
Why is your work in the paper important and why is it exciting? What impact will this have on the field of stem cell research?
In recent years, progress toward therapeutic dividends of embryonic
stem cell research has made tremendous strides. A major breakthrough
has been the routine generation of patient matched pluripotent stem
cells, which has allowed modeling of human genetic diseases in vitro.
The hope is that patient specific stem cells can also provide
cell-based therapies, but much work remains before the yield, purity
and functionality of specific hESC derived cells meets a safe and
effective threshold. Our work has established a standard methodology
for generating functional endothelial cells from hESCs using conditions
that are suited to clinical application. These cells can now be
routinely and economically produced on scales that make pre-clinical
assessment of their efficacy practical in large animal models of
vascular disease.
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