The long-term objective of this research theme seeks to identify the most potent components of particulate matter (PM) and to develop strategies for reducing its health impacts. This project focuses on combustion- derived PM (cdPM), and its research is to link molecular pathways in lung cells that are associated with adverse cellular responses to cdPM and adverse human health effects with (a) specific and environmentally relevant cdPM physicochemical properties and (b) changes in these properties as a result of atmospheric transformationsandconditioning.Theinnovationisbasedontheabilityto(a)reliablysynthesizecdPMunder tightlycontrolledconditionstoobtainspecificproperties,(b)tomimickeyatmospherictransformations,and(c) collect cdPM in a manner that will preserve the properties of interest during exposure of target cells. This approachwillminimizeconfoundingfactorsandenhancethereproducibilityoftheresults,anditwillallowthe projecttoexplorehowthesedistinctphysicochemicalpropertieslinkto:cellularuptake;?toxicity;?inflammatory responses;?CYPenzymeregulation;?andactivationofTRPionchannels.Althoughthesearerelativelystandard measures, these measures are good indicators of in vivo models and human health effects.
The Specific Aimsi nclude:(1)thecompletionofacomprehensivecareerdevelopmentplanthatbuildsknowledgethrough hands-onexperienceandformaltraining;?(2)thesynthesisofcdPMgeneratedunderconditionsthatmimickey atmospheric transformations, resulting in real-world differences in shape, size, and composition;? and (3) the linkingofcdPMphysicochemicalpropertiestopathologicallyimportantoutcomesinprimaryandimmortalized lung cells with in vivo and human-health relevance. Much cdPM exposure is through particle inhalation and interactions with the lung. These research objectives complement the proposal?s comprehensive career development plan that promotes an independent research career for PI, Dr. Kelly. The proposed project focuses on cdPM because it is a significant contributor to atmospheric PM levels, and cdPM emission regulations focus on PM mass concentration. However, changes in cdPM physicochemical properties associatedwithnewfuelsandnewenginetechnologiestendtobeconsideredonlyafterthesechangeshave alreadybeenimplemented,leadingtounintendedconsequences.Thisapplicationoffersanopportunityfora researcher trained in combustion, cdPM generation/characterization to gain skills in biological sciences enabling a more comprehensive and systematic approach to understanding the effects of cdPM physical propertiesonhealthandbiologicaloutcomes.Completionoftheproposedprojectwillprovideconclusivenew findings about how cdPM size, shape, and composition modify biological processes that may be pivotal in linkingairpollutiontocommonlyobservedadverseoutcomesinrespiratorytissue.Thisinformationisessential for developing improved metrics that link the PM?s health effects to health outcomes and for developing exposuremitigationstrategiestailoredtothemostpotentcharacteristicsofPM.

Public Health Relevance

Thisproject?sobjectiveistocompleteanintegratedresearchandcareerdevelopmentplantotransitionthePI toanindependentinvestigator.Theresearchobjectivewillleadtoimprovedmetricsforlinkingparticulatematter (PM)propertiestohealthoutcomesandfordevelopingexposure-mitigationstrategiestailoredtothemostpotent characteristicsofPM.TheprojectfocusesoncombustionPMandseekstoanswerhowcombustionPM?ssize, shape, and composition modify biological processes that may be pivotal in linking air pollution to commonly observedadverseoutcomesinrespiratorytissue.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
1K25ES027504-01
Application #
9224407
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Nadadur, Srikanth
Project Start
2017-01-01
Project End
2021-12-31
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Organized Research Units
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Jaramillo, Isabel C; Sturrock, Anne; Ghiassi, Hossein et al. (2017) Effects of fuel components and combustion particle physicochemical properties on toxicological responses of lung cells. J Environ Sci Health A Tox Hazard Subst Environ Eng :1-12