interview: during my visit to CNIC, we discussed some of the lab's work and why it matters, as well as some broader points, like why I find it exciting that we are wrong all of the time. read more here ->
www.cnic.es/en/noticias/...
We are thankful for the support that allowed us to pursue this important but understudied (& underfunded) area, especially the NIH New Innovator Award (DP2). Also @mskcancercenter.bsky.social @wcm-imp.bsky.social @ahascience.bsky.social @hhmi-science.bsky.social @weillcornell.bsky.social
Although I was originally skeptical that there would be a meaningful effect of MPs on phagocytosis, it is now clear to me I was wrong & that additional, rigorous studies of the cellular and physiological consequences of these environmental pollutants (exposome) are needed. /16
Our fertility data raise important biological & epidemiological questions. We speculate that the cause of male infertility is multifactorial & likely includes both MP-related variables, such as time, type, & route of exposure to MPs, as well as MP-independent variables. /15
Collectively, our data demonstrate that MP accumulation disrupts both efferocytosis & inflammatory phagocytosis & suggests that ineffective efferocytosis may underlie some of the human pathologies thought to be caused by chronic MP exposure. /14
Excitingly, engineering macrophages with Glo1 significantly rescued MP-mediated efferocytosis impairments both in vitro and in vivo! /13
We next had the crazy idea that, maybe, we could give macrophages the ability to combat MGO accumulation by a process my colleague Kayvan Keshari coined 'metabolic engineering'. It turns out, there is an enzyme (called Glo1) that detoxifies MGO in cells. /12
Strikingly, we found increased “MGOylation” (MGO binding) of proteins, including the enzyme G6PD. G6PD is required for efficient degradation of engulfed dead cells. /11
We sought to learn how MPs are causing these defects. The results were striking: The presence of MPs in macrophages engulfing dead cells accumulated the metabolite methylglyoxal (MGO). MGO forms Advanced Glycation End Products, associated w/ many chronic diseases @seckennedy.govpeeps.us /10
Scarily, these effects were not limited to efferocytosis, as MPs also suppressed bacterial, fungal, & antibody-mediated phagocytosis in vitro as well as the phagocytic uptake and killing of A. fumigatus (a fungal infection model) in the lungs of mice in vivo. /9
Using multiple mouse models, we found MP exposure disrupted efferocytosis in the lung, liver, and testis in vivo, negatively affecting each tissue. In the case of the testes, this caused decreased fertility in male mice /8
Specifically, we found that both mouse & human macrophages exposed to MPs internalize fewer dead cells & have significantly delayed digestion of engulfed dead cells in vitro (e.g. alveolar macrophages shown in the image above). /7
Previous studies have shown that your body's macrophages can eat MPs. However, if & how these MPs affect efferocytosis is unknown. Here, we report the alarming finding that exposure to MPs significantly impairs efferocytosis in multiple mice tissues & by human macrophages. /6
One of these essential tasks, the phagocytosis of dead cells (we call it 'efferocytosis'), is the process by which our phagocytes literally engulf your body's dead cells, something that happens as often as 3 million times per second! You can imagine why this matters. /5
These MPs, commonly ingested or inhaled via environmental exposure, first encounter professional phagocytes, such as macrophages (the body's 'big eaters'), that live in all tissues of the body and perform essential tasks. /4
Plastics are a ubiquitous part of everyday life, but growing evidence suggests that the microparticles from plastic degradation, microplastics (MPs), pose a significant threat to human health. /3
Before beginning, this is the first paper from our lab under the new @hhsgov.govmirrors.com @seckennedy.govpeeps.us guidelines for open access. The link to the immediately free version is here: www.sciencedirect.com/science/arti... /2
Those who know me, know I’m not someone who changes his preferences & behaviors lightly. As Ron Swanson said, “I regret nothing. The end.” Well, let me tell you about our new study, out from The Perry Lab @mskcancercenter.bsky.social in @cp-immunity.bsky.social, which is the exception. /1
Perry Lab has published 4 high-profile papers (w/ 5th accepted) in 6 yrs since lab opened yet still can't seem to catch a break/benefit of the doubt at NIH study sections. High-risk research has turned out to be a double-edged sword. I'm now questioning my choices.
It does raise the question of why the thymus hate? There should be a campaign to stop the thymus hate!
I think my lab works on immunometabolism 🤔🤷♂️🤣
Yuval Levin: Have an Argument.
Disengagement—not disagreement—is the real failure of our politics.
www.thefp.com/p/yuval-levi...
If you can't say that political violence, especially murdering someone in cold blood because you disagree with them, is not only morally wrong but anathema to a free country, then I would encourage you to immediately log off and take time for self-reflection.
Cool! Have you built in a way to integrate published phenotypes?
I was interviewed by Nick Jahomes on the Mind & Matter podcast about our study in @nature.com. Nick does a great job asking questions & explaining nitty gritty. Please take time to listen to the episode & if you like it, consider supporting Nick's efforts. mindandmatter.substack.com/p/fructose-m...
Here's what I assume the study is in re: acetaminophen. It's a statistical analysis of a few dozen studies, to be clear, where the majority (especially the high quality ones) show a positive association. Reputable investigators. ehjournal.biomedcentral.com/articles/10....
What's the concern? They awarded it this most recent cycle. www.research.gov/grfp/Login.do
@wcm-imp.bsky.social @weillcornell.bsky.social @mskcancercenter.bsky.social
Congratulations to Ana @anaccodo.bsky.social in my lab and the other awardees. It is a really great acknowledgement of excellent trainees doing cool science.
Makes me miss the talented people back home in AK. Was just back at Forest Fair, another reminder of how great it is there.
