PhD Proposal: Joel Tyson

Joel Tyson, PhD Student

Advisor: 

Elucidating the effects of particulate matter transition metals on lung cells using cell culture assays

Abstract:

There is a growing consensus that particulate matter (PM) exposure from air pollution causes oxidative stress in the body, leading to a plethora of negative health effects. Transition metals, commonly found in particulate matter, have been shown to be major contributors to this toxicity, but current assays of oxidative stress provide unreliable measurements due to nonuniform artifacts caused by the precipitation of transition metals in assay matrices. For example, the most widely used acellular study of PM oxidative potential, the dithiothreitol assay, uses phosphate-based matrices that are known to cause altered precipitation of transition metals including Fe, Cu and Mn in their various, common oxidation states. 

This work aims to provide a robust analysis of the roles of soluble and insoluble Fe, Cu and Mn transition metals in causing damage to lung cells using cell culture assays and analyze the effects and fate of the metals in physiological solutions. Using monolayer cultures of lung cells, I will measure DNA damage, cytotoxicity, cell membrane integrity, intracellular radical species, and inflammatory cytokines. I will use dynamic light scattering and inductively coupled plasma mass spectrometry measurements of precipitate formation in cell culture media with and without fetal bovine serum, cell culture supernatant and simulated lung fluid to determine the fate of the metals in the cellular milieu. In addition, I will add a common class of organic species found in PM, polycyclic aromatic hydrocarbons, to the metal solutions to test for any synergistic effects in toxicity with any of the metal species. I will also perform functional assays using air-liquid interface cultures which better mimic lung physiology. The results of the physiological assays will be assessed for transcriptional differences. 

Agenda:

• 8:45 am: Meeting room will open  
• 9:00 am: 45 min presentation will be open to the public with Q&A.
• Followed by a closed session with the committee and PhD Student.