The academic lab is a screwball cross-section of personalities. There is everyone from the omnipotent lab manager and the timorous undergraduate to the idealistic graduate student and the grizzled post-doc or any other combination thereof.

With each personality comes a different level of lab experience in terms of time spent in the lab. Because people don’t enter the lab as a unit, the time together for most people is short. And during their short time together, everyone is looking to move forward in their career stage. 

The singular constant in this cabal is the principal investigator (PI) who will be there for everyone’s time in the lab, from start to finish. The PI sets the culture for the lab—how people interact and how people become scientists. How then does a PI build comradery among this rag-tag group? How can the team work together to advance the lab but at the same time advance everyone’s perspective career goals?

This article was originally published in the January 2023 issue of The Physiologist Magazine. 

The link to the full article can be found here.

Thromboembolic events secondary to rupture or erosion of advanced atherosclerotic lesions are the underlying cause of most heart attacks or stroke and are the leading cause of death in the United States and worldwide. Whereas there is general agreement that atherosclerosis is a chronic inflammatory disease, multiple large clinical trials of drugs that globally inhibit inflammation have failed to get FDA approval due to them having modest or no beneficial effects on the incidence of a fatal or non-fatal heart attack or stroke, and an increase in lethal infection because patients are immuno-compromised.

We postulate that a major reason for the failure of global anti-inflammatory agents is because they inhibit not only detrimental chronic pro-inflammatory responses that exacerbate atherosclerosis, but also evolutionarily conserved beneficial acute inflammatory processes necessary for resistance to infection, resolution of inflammation, and tissue injury-repair processes important for enhancing the stability of atherosclerotic lesions and reducing the chance of rupture or erosion. Studies in this proposal will use novel mouse models and analysis methods to determine if selective inhibition of interleukin-6 (IL-6) trans signaling, which is believed to be a key mediator of the transition from acute (beneficial) to chronic (detrimental) inflammation, promotes formation of more stable atherosclerotic lesions and a reduced probability of lesion rupture or erosion but without impaired immuno-competence. If so, results would be of major significance in that they would suggest that human clinical trials should focus on testing selective IL-6 trans inhibitors not global inhibitors of IL-6 responses as is currently the case with a recently initiated large Phase 3 clinical trial.

Sepsis accounts for more hospital deaths per year than any other condition in the United States, and the disease is currently devoid of any targeted pharmacological intervention. Critical to understanding how inflammation affects vascular barrier function is that endothelial cells throughout the circulatory system are not homogenous. Inflammation specifically affects vascular permeability through effects on the venous endothelium. Thus, a mechanistic view of how venous endothelial barrier function is regulated is essential.  Our current understanding of vascular barrier function does not account for endothelial heterogeneity and the unique cell adhesion and signaling pathways specific to each endothelial cell type. Purinergic signaling has been identified as a key regulator of endothelial permeability; however the cellular pathway allowing for simultaneous regulation of the purine response and tight junctions has not been explored in detail. Our work will focus on the role of the purine-release channel Pannexin 1 in venous endothelium and potentially new pharmacological interventions for treating sepsis.