I also had never seen this format until our preprint was reviewed. Seems to be mostly preprint-focused. Anyways, thanks for sharing the biorxiv link 😊

Thanks, Tom!

Thank you Alissa! Moving, starting up the lab, and getting this submitted felt like an extreme sport 😅 Very grateful to have a supportive community at NIH and the always inspiring early career TB research crew to look up to (like you 😉)

P.S. SO bummed I couldn't be at KS to catch up!

But microbial factors could be at play. Especially since we know Mtb resides in the caseum and prompts macrophage necrosis. We are hoping some of our organoid work will help us decouple the chicken-and-egg relationship between hypoxia and bacterial burden.

This is a great question. To try to get at it, we are currently evaluating granulomas from an earlier timepoint of infection. These grans have much higher CFU but less hypoxia. The main thrust of hypoxia appears to be caseation and it may be exacerbated by the degree of neutrophil influx...

Thank you! We are excited to finally be able to share it with everyone.

Thanks for tuning in! Please feel free to reach out with any feedback or questions on our preprint. (20/20)

The senior authors on this paper (especially my PhD advisor, Mike Angelo) have been the most incredible mentors to me and the wind behind my sails as I transitioned from Stanford to the NIH to start my own group. Despite...everything 🙃...I am excited for the cool science we are cooking up! (19/20)

In Nov 2023 I started my lab at the NIH (the Spatial Immunology Unit) as an Independent Research Scholar. We are combining spatial mapping of tissues with functional assays in organoid models to define the principles of immune programming during infection and inflammation with a focus on TB. (18/20)

A HUGE thank you my co-author, Alea Delmastro, who began as my undergrad mentee in 2018, adapted MIBI for NHP tissues (no small feat), and then became my co-lead on this study. Here we are celebrating after we stained the study cohort during the pandemic (a culmination of 3 years of work). (17/20)

I would like to thank the extremely creative, talented, and hard-working individuals who worked on this study. This team spans 8 institutions and much of this work was done in the depths of the pandemic. I am so grateful for their brilliance, collaboration, and friendship. (16/20)

Check out the full preprint for more details, our perspective on what this means for clinical management of TB, and parallels between hypoxia in TB granulomas and other settings of inflammation. (15/20) www.biorxiv.org/content/10.1...

Moral of the story? Granuloma hypoxia is associated with pathologic immune cell states, dysfunctional cellular organization of the granuloma, and a near-complete blockade of lymphocyte infiltration that would be required for a successful host response. (14/20)

Lastly, we confirmed that the same phenomenon of immunometabolic zonation is present in human pulmonary TB, underscoring the translational relevance of our findings. (13/20)

We also applied QUICHE (from the talented Jolene Ranek in the Angelo lab) to map the spatial networks of low- versus high-bacterial burden granulomas. With this analysis we found that hypoxia-associated spatial niches were over-represented in high-bacterial burden granulomas. (12/20)