The Department of Chemistry at North Carolina State University!
@ncstatechem.bsky.social

Wow, you have a lot of students!!!

Cookie goals!!!

Your “Structure of an R01” was the best grant writing guide I had as a new (and unconnected) Assistant Professor. I have used it in classes I teach and shared it with many Jr colleagues. Thank you for demystifying the system for many of us and helping to make the process more accessible to all.

Congratulations Ken!!!!

Thank you so much Riccardo!

Thank you so much Dori!!! 🥰

Finally, we show why most work with Seahorse should be done at low concentrations and early time points. Meaning, working below the cytotoxicity IC50 values, and after only short incubations (1-2 hrs). Otherwise, you get misleading data.
We suggest best practices for researchers to avoid pitfalls.

Glycolysis increases the acidity of the tumor microenvironment (TME), and this is generally believed to be immunosuppressive. Thus, PDT may reduce the immunosuppressive TME, encouraging combination of PDT with immunotherapies.

This could provide a strong rationale for PDT fractionation, as PDT requires O2, and there will be MORE O2 available when OXPHOS is inhibited. It might be possible to get more treatment bang for the photon buck with fractionated PDT treatments.

This is great news is you want to use photocages and not alter metabolic processes!
And it has real implications for PDT:
PDT induced metabolic reprograming, with OXPHOS and glycolysis shut down by the PDT photosensitizes. This indicates that PDT and might synergize with metabolic disruptors.

Many groups are using the Seahorse Metabolic Analysis to study compounds. We investigated the impact of light-activated molecules on oxidative phosphorylation and glycolysis. We found that Ru(II) PDT photosensitizes have a significant impact on metabolism. Ru(II) photocages do not.

These include working below the cytotoxicity IC50 values, and after only short incubations (1-2 hrs). Otherwise, what is observed may be a downstream effect of other biological processes.

What are the implications?
PDT may be effective for metabolic reprograming and might synergize with metabolic disruptors. This could also have implications for combination PDT with immunotherapies.
PACT agents can be used as photocages without disrupting metabolism.
We also suggest best practices.

We found two thing:
1) PDT agents shut down both OXPHOS and glycolysis, and induce senescence. PACT agents do not.
2) It is essential to do time and concentration dependent studies, and most work should be done at low concentrations and early time points. Otherwise, you get misleading data.

Love this!!!

Yay, thank you Catherine, this is great!!!
Now we just need to get more of the community to migrate over here!