Travis Knuckles, Ph.D.
	Research Assistant Professor of Physiology and Pharmacology Graduate Training: North Carolina State University Fellowship: Lovelace Respiratory Research Institute
	Office: 3078A-HSN Lab: 3138-HSN PO Box 9229 Morgantown, WV 26506	Email: tknuckles@hsc.wvu.edu Phone: 304-293-1007 Fax: 304-293-5513

Research Interests:

Figure 1:SEM images of collected particles.  A) A representative image of particles collected from an active surface mine.  B) Nanoparticles (nano-TiO2) collected on a filter during an inhalation exposure.

Figure 2: Autoperfused flow chamber.  A) Leukocyte adherence under control conditions.  B) Treatment with PMA dramatically enhances blood leukocyte adherence.

Figure 3: A typical rat SNA and blood pressure trace from telemetry.  A) SNA measurements during sham exposure.  B) SNA is increased during nanoparticle exposure.

Air pollution exposure is an international crisis that affects all communities and people of all walks of life.  Furthermore, efforts to reduce air pollution levels have not kept pace with industrial and urban growth.  Air pollution is made up of a large body of diverse solids, liquids, and gases suspended in air.  Of those, particulate matter (PM) is deemed one of most important in terms of the cardiovascular health effects.  Moreover, the health effects of PM can be delineated by size, as smaller particles (<0.1 μm) are generally considered to be more toxic.  As with many toxicants, the health effects of PM are greater in sensitive populations, such as the young, elderly, or individuals with pre-existing conditions.  However, the specific mechanisms by which PM affects the cardiovascular system remain unclear.  Our laboratory is currently investigating several aspects of cardiovascular health consequences following pulmonary particle exposure.  We employ several techniques to determine cardiovascular effects of PM including:  intravital microscopy, isolated microvessels, autoperfused flow chambers, and radiotelemetry.  Using these techniques we have focused our efforts on ambient particles from active surface mines (Figure 1A), and engineered nanomaterials (e.g. TiO2 [Figure 1B]).  Our overarching goal is to mechanistically link inhalation exposure to remote tissue effects. Specific projects are outlined below.

1.  Previous work in our laboratory has demonstrated an alteration in vascular wall nitric oxide (NO) following PM exposure.  These previous studies have shown that following PM exposure NO is oxidized by reactive oxygen species (ROS) prior to utilization by the vascular smooth cells.  However, what was not known was how the arteriolar network was still responsive to certain agonists.  Our current work has demonstrated that in the absence of NO arterioles rely more on prostacyclin (PGI2) as a vasodilator.  Furthermore, it appears that the exposure to PM increases sensitivity to other cyclooxygenase products like thromboxane A2.  Future research will focus on solidifying the mechanistic links between PM exposure and microvascular toxicity.

2.  We have previously demonstrated that pulmonary particle exposure enhances leukocyte rolling and adherence in post-capillary venules.  In vivo enhanced leukocyte adherence and rolling is associated with progression of vascular diseases such as atherosclerosis as well as increased infarct size in acute myocardial infarction.  However, it is not known what specific adhesion molecules are induced following PM exposure nor is it known the effect PM has on leukocyte adherence and rolling.  Our laboratory has developed an autoperfused flow chamber to identify specific adhesion molecules that may be altered following PM exposure.  Figure 2 shows labeled blood leukocytes under control conditions (Panel A) or stimulated with PMA (Panel B) adhering to a glass chamber under flow conditions. 

3.  Our laboratory has recently shown indirectly that PM alters sympathetic influence on the microvasculature.  In order to further investigate this, we developed a telemetry model to identify specific changes following particle exposure in sympathetic nerve activity (SNA).  Using a radiotelemetry device we are able to capture in real time SNA before, during and after exposure to particles.  Figure 3 depicts a typical integrated SNA trace with blood pressure under sham (Panel A) and PM (Panel B) exposure conditions. 

Selected Publications: