Vanderbilt University scientists are cheering this year’s Nobel Prize in Medicine for recognizing the discovery that mature cells can be “reprogrammed” into other cell types — a finding which they said has electrified their work.
The work by new Nobel Laureates Sir John Gurdon and Shinya Yamanaka and “others who were not recognized … literally transformed our view of the very nature of cells,” said Mark Magnuson, M.D., director of the Vanderbilt Center for Stem Cell Biology.
“We can no longer look at mature cells as being immutable and fixed,” Magnuson said. Rather, the ability to convert them into “pluripotent” stem cells and then into completely different cell types has “immense” implications for the fields of tissue regeneration and personalized medicine, he said.
Magnuson, professor of Molecular Physiology and Biophysics, Cell and Developmental Biology and Medicine, holds an endowed Louise B. McGavock Chair. He directs a research project aimed at making new pancreatic beta cells from other cell types as a potential treatment for diabetes.
Magnuson’s view is echoed by Christopher V.E. Wright, D.Phil., whose graduate and postdoctoral work at Oxford University and UCLA was mentored by Gurdon’s former research fellows. “I am extremely proud and constantly aware that Gurdon is my scientific grandfather,” said Wright, who directs the Vanderbilt Program in Developmental Biology.
Gurdon and Yamanaka’s discoveries helped moved science to “within real grasp of … being able to use pharmacological interventions to come up with cellular replacement therapies, and also to gain a more complete control and dominance over cancer in its multiple incarnations,” he said.
Wright, also a Louise B. McGavock Chair and professor of Cell and Developmental Biology, is studying development of the pancreas. “A deeper understanding may provide surprising therapeutic angles by defining conditions that allow the controllable reprogramming of endodermal or pancreatic cell populations,” he and his colleagues reported this summer.
For Charles Hong, M.D., Ph.D., Yamanaka’s work in particular “gives us the realistic possibility that human heart cells can be readily made, studied in detail and perhaps even put to use to treat patients dying of heart disease.”
“All this is still at its infancy, but there has been tremendous progress since 2006,” said Hong, whose lab has developed the capability to engineer sheets of heart cells from patients’ skin cells. See Hong’s lab-grown heart tissue in action:
Kevin Ess, M.D., Ph.D., and his colleagues are using reprogrammed human skin cells to study multiple neurological disorders including tuberous sclerosis complex (TSC), one of the most common genetic causes of seizures and autism in children.
By generating human neurons from patient-derived stem cells, they expect to find clues to the development of TSC and, in a larger sense, understand more fully the molecular mechanisms that guide brain development.
Aaron Bowman, Ph.D., and his colleagues are generating human brain cells that are an exact genetic match to cells from patients with Parkinson’s or Huntington’s disease.
In this way, “we can … study whether these cells have increased sensitivity to metals or pesticides found in the environment,” Bowman said. “We can explore what protective measures or treatment strategies may work best for each individual patient, by testing cells made from (their) stem cells.”
Magnuson, Wright, Hong, Ess and Bowman’s research is supported by the following grants from the National Institutes of Health: 5U01DK089523; 5U01DK089570; 5R01HL104040 1R01NS078289; and 5R01ES016931. Ess is also supported by the Doris Duke Charitable Foundation. Bowman is also supported by the Peterson Foundation for Parkinsons and by the Parkinson Support Group of East Tennessee.
