Environmental Factor, March 2009, National Institute of Environmental Health Sciences
ONES Awardee Speaks at NIEHS
By Eddy Ball
In a lecture on February 6, NIEHS grantee Sven-Eric Jordt, Ph.D., discussed the latest developments in his basic research on the mechanisms of transient receptor potential (TRP) channels. He also offered insight into potential applications of his findings in protecting people from tear gas and other warfare and industrial agents and, possibly, in preventing or treating symptoms of asthma and allergies.
His talk, titled "Sensory TRP Channels in Respiratory Reflex Control and Inflammation," was a part of the NIEHS Laboratory of Respiratory Biology (LRB) Lecture Series and was hosted by Principal Investigator Stephanie London, M.D.
A professor in the Department of Pharmacology at the Yale University School of Medicine (http://info.med.yale.edu/pharm/faculty/index.php?bioID=39) , Jordt is a member of the first group of Outstanding New Environmental Scientists (ONES) awardees. He also enjoys the distinction of being the first NIEHS extramural grantee (see story) to receive one of the prestigious Presidential Early Career Awards for Scientists and Engineers (PECASE). In his opening remarks, Jordt expressed his appreciation for the "phenomenal support I have received from NIEHS."
As Jordt explained, TRP channel receptors are part of an early warning system of sensory neurons during injury and chronic painful conditions that trigger tears, sneezing, neurogenic inflammation, pain and respiratory constriction in the upper airways upon exposure to noxious agents, temperature and environmental toxicants with irritant activities. In his early work with TRPs, Jordt discovered one - transient receptor potential ankyrin 1 (TRPA1) - that proved to be especially promising for preventive and therapeutic applications.
Through a process of elimination in a series of systematic experiments that included wild type and knockout mice, Jordt discovered that TRPA1 was essential for mammalian hypersensitivity reactions to a wide range of irritants. These included mustard oil, chlorine and acrolein, an oxidized hydrocarbon present in cigarette smoke, exhaust fumes and smoke from other sources.
As his work progressed, Jordt was able to add to the list of noxious industrial and warfare-agent compounds that are TRPA1 agonists. He found that several other major threats to respiratory health also activate TRPA1, including chlorine, tear gases, and isocyanates, such as the methyl isocyanate released during the industrial accident in Bhopal, India that caused more than 3000 immediate deaths and thousands more afterwards.
In a study (https://www.ncbi.nlm.nih.gov/pubmed/19036859?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum) using a TRPA1 antagonist, HC-030031, Jordt and his colleages showed that they were able to prevent the acute sensory irritation caused by exposures to isocyanates and tear gases. They speculated further that "TRPA1 antagonists may also be useful for post-exposure treatment, reducing sensory irritation and, potentially, preventing adverse long-term health effects elicited by neurogenic inflammatory mechanisms."
Jordt's tear gas research is part of the trans-NIH CounterACT (Countermeasures Against Chemical Threats) Research Network (https://www.ninds.nih.gov/research/counterterrorism/counterACT_home.htm) , an initiative led by the National Institute of Neurological Disorders and Stroke (NINDS) involving grants from NIEHS and seven other institutes. His lab has received additional support from the American Asthma Foundation, Health Effects Institute and Connecticut Department of Health.
Jordt's talk at NIEHS was the second he gave during his visit last month to the Raleigh-Durham-Chapel Hill area. On February 5, he made a presentation as part of the Ion Channel Research Unit Seminar Series at Duke University in Durham.