Understanding individual susceptibility to environmental toxicants
By Carol Kelly
The genetic blueprint that makes each of us unique also influences our susceptibility to environmental toxicants. Deciphering the complexities of this interaction is what motivates Aaron Bowman, Ph.D., an assistant professor in the Department of Neurology at Vanderbilt University. During his Keystone Science Lecture Seminar Series presentation Nov. 14 at NIEHS, Bowman described how his lab uses induced pluripotent stem cells (iPSCs) to take a personalized approach to investigating environmental health and neurodegenerative disease risk.
“We are actively seeking to understand how individuals at risk for certain neurodegenerative diseases, such as Parkinson's disease and Huntington's disease, may exhibit altered susceptibility to metals in the environment,” said Bowman.
His lab is pioneering a patient-specific approach to test differential neurotoxicity and gene-environment interactions, using differentiated neural progenitors and neurons from patient-specific iPSCs.
A type of undifferentiated cell, iPSC is a useful tool for modeling diseases. These cells are generated by injecting specific gene control agents into an adult cell, which can then be taken back to its early developmental, or stem cell, form. Although difficult to create, iPSCs do not provoke the ethical considerations associated with using human embryonic stem cells. In recognition of this breakthrough technology, the method’s inventor, Shinya Yamanaka, M.D., Ph.D., won the 2012 Nobel Prize in Physiology or Medicine.
“Working with human iPSCs is costly in both dollars and time, but the technology potential makes it worthwhile,” said Bowman. “My lab has been applying iPSC technology to neurotoxicity research for more than three years. We have established protocols to generate iPSC lines and differentiate them down neural forebrain and midbrain lineages.”
Bowman’s lab is investigating the influence of manganese exposure in Huntington’s disease and Parkinson’s disease. He and his colleagues hope to define mechanisms of neuronal dysfunction and learn the basis of selective neuropathology, by characterizing the molecular function of disease genes and their interaction with environmental toxicants under both normal and pathological conditions.
Bowman is a ONES Awardee
Bowman won an NIEHS Outstanding New Environmental Scientist (ONES) award in 2008 for examining the mechanisms behind the interaction between manganese and Huntington's disease. The support from NIEHS enabled him to develop an approach to use patient-derived stem cell models to better understand the connections between genetic and environmental risk factors.
“My interest in the role of environmental factors in disease began with a discovery of a unique interaction between exposure to the metal manganese and the gene associated with Huntington's disease,” said Bowman. “In the discovery of an unexpected environmental risk factor, I became intrigued by connections between disease and our environment.”
He received his Ph.D. in biomedical sciences in 2000 from the University of California, San Diego, and did his postdoctoral fellowship training at Princeton University and Baylor College of Medicine.
(Carol Kelly is a research and communication specialist with MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)