The U.S. Department of Defense has awarded UNMC $1 million to conduct research targeted toward lessening the harmful effects of chemical warfare agents.
The money will be used to expand the capabilities of the Protein Structure Core Facility in the Eppley Cancer Research Institute at UNMC through the purchase of an ultra-sensitive ion trap mass spectrometer. Oksana Lockridge, Ph.D., associate professor at the Eppley Institute, is the principal investigator in the research study.
The funding will be provided through the fiscal year 2003 Department of Defense budget. “As a member of the Senate Armed Services Committee, Sen. Ben Nelson was very helpful in procuring this funding,” said Thomas Rosenquist, Ph.D., vice chancellor for research. “We appreciate the work that our congressional delegation members and their staffs perform in helping UNMC obtain critical funding to advance our strategic priorities.”
As part of the Protein Structure Core Facility at the Eppley Institute, the mass spectrometer will be available for analysis of samples submitted by other scientists on the UNMC campus, Dr. Lockridge said. She will use the device to try to determine what proteins are modified when people are exposed to nerve agents used in chemical warfare and then develop biomarkers that would indicate exposure to these agents. She will be studying between 30 to 40 proteins in her study.
Support from the Department of Defense
This marks the second time Dr. Lockridge has received funding from the U.S. Department of Defense. Earlier this year, she received a four-year, $1.7 million grant to try to develop an efficient way to protect humans against the toxic effects of nerve agents used in chemical warfare. Nerve agents interfere with the functioning of the nervous system and are chemicals related to certain pesticides.
Chemical warfare and a genetically engineered mouse
Chemical warfare was used in the 1995 Tokyo subway terrorist attacks, when members of a cult placed sarin gas on subway trains, killing 12 and injuring more than 5,500. Nerve agents such as sarin, VX and tabun are inexpensive and easy to manufacture and have been used as weapons of terrorism and defense mechanisms for third world countries.
A unique, genetically engineered mouse has been developed at UNMC, Dr. Lockridge said. This mouse has led to the discovery of previously unexpected protein targets for chemical nerve agents. When this mouse was tested for sensitivity to the nerve agent, VX, it showed signs of toxicity at doses that proved the presence of previously unknown protein targets.
The chemical and biological nature of these targets is not yet known.
The mass spectrometer will aid Dr. Lockridge in identifying new protein targets, and the information learned should be beneficial in better protecting people from the toxic effects of chemical warfare agents.
Breathing 10 milligrams — the weight of a grain of rice — of VX, the deadliest nerve agent, can kill in 15 minutes. Symptoms of nerve agent exposure include reduced vision, diarrhea, vomiting, paralysis and respiratory failure. Ultimately, individuals experience convulsions and go into a coma.
Research relevant to farmers
Because of the similarity in makeup of chemical warfare agents and pesticides, Dr. Lockridge’s research also is relevant to Nebraska farmers. About 80,000 cases of pesticide poisoning are reported annually in the United States. Common pesticides such as roach and ant killers are in the same class of chemicals as the chemical nerve agents.
Expertise in developing biomarkers
“This funding helps reaffirm UNMC’s expertise in developing biomarkers that indicate exposure to certain pesticides, as well as in the gene and protein therapy used against chemical warfare agents,” Dr. Rosenquist said. “It is further indication of how strong UNMC has become in its bioterrorism programs.”
“Biomarkers for low dose exposure are needed because people often do not know the cause of their ill health,” Dr. Lockridge said. “For example, veterans with Gulf War illness don’t know whether their symptoms are caused by something they came in contact with in the Persian Gulf or whether they are suffering from some sort of normal illness. Likewise, farmers who have Parkinson’s disease are uncertain if exposure to pesticides might have caused their disease.
“The mass spectrometer will aid in identifying new targets and subsequently in the diagnosis of exposure. Once the proteins involved in these illnesses are identified, it may be possible to treat the diseases with gene or protein therapy.”
The total cost for the mass spectrometer is about $1.8 million, so UNMC will bear the remaining $800,000 in costs associated with this project, Dr. Lockridge said.