While the US science ship is shaking, on a brighter note: two new preprints from the lab. In the first, we identify a long sought, enzyme of eicosanoid metabolism, 5-HEDH, which regulates inflammatory lipid synthesis and breakdown as a function of tissue redox state. www.biorxiv.org/content/10.1... - ThreadSky

niethammerlab.bsky.social • 19 days ago

While the US science ship is shaking, on a brighter note: two new preprints from the lab. In the first, we identify a long sought, enzyme of eicosanoid metabolism, 5-HEDH, which regulates inflammatory lipid synthesis and breakdown as a function of tissue redox state.
https://www.biorxiv.org/content/10.1101/2025.02.05.636725v1

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niethammerlab.bsky.social•19 days ago

5-HEDH controls 5-KETE (5-oxoETE) production. 5-KETE is a powerful leukocyte chemoattractant from fish to primates. Here we identify a novel function for this poorly studied lipid pathway in protecting the mucosal linings of the gut from oxidative damage.
https://www.biorxiv.org/content/10.1101/2025.02.05.636712v1

niethammerlab.bsky.social•19 days ago

5-HEDH marks a novel, "metabolic"mode of redox sensing: not via reversible thiol oxidation, but by measuring the cytosolic NADP+/NADPH ratio. Thereby, it directly links inflammation to NADPH consumption by NADPH oxidases or antioxidant defense circuits. 5-HEDH remained elusive for the past 30 years.

niethammerlab.bsky.social•19 days ago

The red box marks the KEGG ID that we now fill with a gene name. I was searching for 15 years for the molecular mechanism through which H2O2 exerts chemotaxis (Niethammer et al., 2009). With Yanan's discovery, this long & facinating journey comes to a happy end 🍾.

niethammerlab.bsky.social•18 days ago

Miklos then serendipitously discovered a surprising, non-immunological role for 5-KETE signaling (see 2nd preprint): It protects the gut mucosa against oxidative DNA lesions, apoptosis, leakage (see below images) and infection through inducing anti-mutagenic enzymes called "Nudix hydrolases" 🥂.

niethammerlab.bsky.social•18 days ago

Miklos is currently testing if 5-KETE, through the mucoprotective mechanism he discovered, acts as a paracrine tumor suppressor. Interestingly, the 5-KETE receptor (OXER1) is inactivated by hotspot frameshift mutations in various mucosal tumors from patients (see below).

niethammerlab.bsky.social•18 days ago

If the pathway is really so important, why have so few researchers studied its physiological functions before? Answer: OXER1, like many other biomedically important genes, is not conserved in our main preclinical animal model, the mouse. But zebrafish have it!
https://www.eurekalert.org/news-releases/976352

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