Eddie Rashan

I received this award as a second year student, and it was transformative and a big part of the reason I persisted. They are making things harder just for no reason.

I remember the days when we recognized that STEM fields were a worthy national investment 🤦🏾‍♀️

Wildfire smoke induces GM3 ganglioside lipid accumulation and transcriptomic shifts in mouse lung tissue: A smoke signal story Wildfire smoke is a growing concern due to continually rising exposures and links to numerous adverse health effects. Lipids are essential regulators …

If you’re looking for some exciting reading to take into the weekend with you, please check out Haley’s first, 1st-author paper published in Science of the Total Environment this week! You won’t want to miss these wildfire smoke induced lipid changes!🔥💨 www.sciencedirect.com/science/arti...

A pleasure to write this short review on lipid droplets for
@jcb.org together with Will Prinz and amazing artist Emma Reynolds!

We discuss 5 pervasive questions surrounding these remarkable little lipid organelles.

doi.org/10.1083/jcb....

Organelle-Targeted Laurdans Measure Heterogeneity in Subcellular Membranes and Their Responses to Saturated Lipid Stress Organelles feature characteristic lipid compositions that lead to differences in membrane properties. In cells, membrane ordering and fluidity are commonly measured using the solvatochromic dye Laurdan, whose fluorescence is sensitive to lipid packing. As a general lipophilic dye, Laurdan stains all hydrophobic environments in cells; therefore, it is challenging to characterize membrane properties in specific organelles or assess their responses to pharmacological treatments in intact cells. Here, we describe the synthesis and application of Laurdan-derived probes that read out the membrane packing of individual cellular organelles. The set of organelle-targeted Laurdans (OTL) localizes to the ER, mitochondria, lysosomes, and Golgi compartments with high specificity while retaining the spectral resolution needed to detect biological changes in membrane ordering. We show that ratiometric imaging with OTLs can resolve membrane heterogeneity within organelles as well as changes in lipid packing resulting from inhibition of trafficking or bioenergetic processes. We apply these probes to characterize organelle-specific responses to saturated lipid stress. While the ER and lysosomal membrane fluidity is sensitive to exogenous saturated fatty acids, that of mitochondrial membranes is protected. We then use differences in ER membrane fluidity to sort populations of cells based on their fatty acid diet, highlighting the ability of organelle-localized solvatochromic probes to distinguish between cells based on their metabolic state. These results expand the repertoire of targeted membrane probes and demonstrate their application in interrogating lipid dysregulation.

The 4 chemically targeted Laurdan derivatives (for mitochondria, ER, lyso/endosomes, and the Golgi) that we published last year are now available (at a pretty reasonable price) from Avanti Polar Lipids (cat #880194, 880197, 880193, 880196). These have been very popular! pubs.acs.org/doi/full/10....

Quantitative imaging of lipid transport in mammalian cells - Nature Directional, non-vesicular lipid transport is responsible for fast, species-selective lipid sorting into organelle membranes.

Quite a week for #lipidtime: phenomenal study using bifunctional lipid probes to quantify intracellular lipid transport from @nadlerlab.bsky.social and colleagues is now out @nature.com! www.nature.com/articles/s41...

Grrrr. We don't call protein phosphorylation or acteylation epiproteomics. So let's not call RNA modification epitranscriptomics. In fact, realisitically, epigenetics has so many definitions, some of them non-overlapping, that this whole epi-XXXX (genetics/genomics whatever) is just not helping us.

The source of dietary fat influences anti-tumour immunity in obese mice - Nature Metabolism This study shows that animal-based high-fat diets accelerate tumour growth and impair anti-tumour response to melanoma in obese mice, whereas plant-based high-fat diets do not.

This was a labor of love requiring lots of teamwork over years, repeating in 3 locations! Thanks to all the lab over the years, giving their time generously to this team project, & our wonderful collaborators. The source of fat matters for anti-tumor immunity 🐄🐖🧈🌴🫒🥥
www.nature.com/articles/s42...

Conservation and divergence of metabolic phenotypes between patient tumours and matched xenografts - Nature Metabolism Rao and Cai et al. perform a detailed metabolic comparison between primary tumours from patients and their matching xenografts, which identify conserved as well as divergent metabolic patterns.

1/Patient-derived xenografts (PDXs) are used in preclinical testing of cancer therapies, including metabolic therapies. We determined which metabolic properties are retained, and which are lost, when melanomas from patients are implanted and passaged as PDXs in mice.
www.nature.com/articles/s42...

Super excited to share new review on metabolic stress and adaptations in pancreatic cancer to these stresses from @cssheehan.bsky.social
jci.org/articles/vie... 1/6

What’s Your Story? 2025 Contest Winners The Scientist is excited to announce the winners of our 2025 science writing contest!

Super excited for Niemi lab grad student Hannah Pletcher, who placed second in the recent "What's Your Story" Sci-comm writing contest put on by The Scientist! Read more about the contest, as well as Hannah's winning entry, here: www.the-scientist.com/what-s-your-...
#ProudPI

ACAD10 and ACAD11 enable mammalian 4-hydroxy acid lipid catabolism - Nature Structural & Molecular Biology Rashan, Bartlett and colleagues show that mammalian 4-hydroxy fatty acids are primarily catabolized by ACAD10 and ACAD11 (atypical mitochondrial and peroxisomal acyl-CoA dehydrogenases, respectively) ...

AND IT'S DONE! A 🧵 on our recent article now out in @natsmb.nature.com! Co-led with @abbybartlett.bsky.social, Pagliarini Lab, @judisimcox.bsky.social, we find ACAD10/11 are NOT like other acyl-CoA dehydrogenases and instead catabolize atypical lipids called 4-hydroxy acids 🤯 doi.org/10.1038/s415...

Thank you, CJ! Hope you and your lab are well.

Yes!! WOOHOO!

Very excited to see this work with @edreesrashan.bsky.social published in @natsmb.nature.com ! #metabolism #AmazingACADs 🤩

It was a privilege to work on a project that allow us to span multiple disciplines and reveal new fundamental biology. Thank you to our funding support, incl. from the NIH, @hhmi.org , and institutional support @washumedicine.bsky.social @uwbiochem.bsky.social @morgridgeinstitute.bsky.social

We hope our findings will spur future studies to clarify how these enzymes and the regulation of 4-HAs underlie human health and disease. There is much to learn about how 4-HAs contribute to whole body metabolic flexibility and their tissue- and organelle-specific functions!

Lastly, we wanted to determine how dysfunctional 4-HA catabolism affects physiology and generated ACAD11 KO mice. Disruption of ACAD11 in vivo leads to accumulation in plasma 4-HAs, higher susceptibility to diet-induced fat gain, and dysfunctional adipogenesis. 🧐

If they have similar activities, are ACAD10/11 redundant in cells? Our metabolomics results suggest they are not! ACAD10 is in mitochondrial and ACAD11 is peroxisomal, and we propose that their differential localization enables cells to catabolize a wider range of 4-hydroxy acids.

Second, 4-phosphoacyl-CoA serves as a substrate for the ACAD domains, which convert it into 2-enoyl-CoA using a “redox-neutral” FAD-dependent mechanism. ACAD10/11 are unable to oxidize saturated acyl-CoAs and use a specialized motif to recognize 4-phosphoacyl-CoA.🤯🤯

How do they pull off the job? First, they use N-terminal kinase domains that specifically recognize and phosphorylate 4-hydroxyacyl-CoA. This phosphorylation is crucial for priming the elimination of the “FAO-incompatible” 4-hydroxyl group.

Using rigorous biochemistry/cryo-EM, we demonstrate that ACAD10/11 convert 4-hydroxyacyl-CoAs into 2-enoyl-CoA intermediates that can enter the FAO pathway. They both conduct a multi-step reaction that centers around a key (and 🧊very cool🧊) PHOSPHORYLATED acyl-CoA intermediate.

Motivated to understand the biology of 4-hydroxy acids (4-HAs) in mammals, we sought to discover and study the enzymes responsible for their metabolism. It was a 3AM bacterial homology analysis that led us to think of ACAD10 and ACAD11 as likely candidates for this pathway (see Figure 1)

Fatty acid B-oxidation (FAO) is the primary pathway by which fatty acids are catabolized. However, some fatty acids are modified and need to be fixed to become “FAO-compatible”. One such class is 4-hydroxy acids, which are present in diet and living systems including humans.

ACAD10 and ACAD11 enable mammalian 4-hydroxy acid lipid catabolism - Nature Structural & Molecular Biology Rashan, Bartlett and colleagues show that mammalian 4-hydroxy fatty acids are primarily catabolized by ACAD10 and ACAD11 (atypical mitochondrial and peroxisomal acyl-CoA dehydrogenases, respectively) ...

AND IT'S DONE! A 🧵 on our recent article now out in @natsmb.nature.com! Co-led with @abbybartlett.bsky.social, Pagliarini Lab, @judisimcox.bsky.social, we find ACAD10/11 are NOT like other acyl-CoA dehydrogenases and instead catabolize atypical lipids called 4-hydroxy acids 🤯 doi.org/10.1038/s415...

Paraoxonase-like APMAP maintains endoplasmic-reticulum-associated lipid and lipoprotein homeostasis Here, Paul et al. show that APMAP is an ER-localized paraoxonase-like enzyme that suppresses lipid oxidation and redox stress at the ER network. APMAP loss leads to ER stress, redox disruption, phosph...

Proud present our latest work led by Blessy Paul, now in Developmental Cell @cellpress.bsky.social.

Here, we characterize an ER-localized antioxidant enzyme in humans and Drosophila that acts as a lipid quality control factor to suppress ER lipid oxidation.

www.cell.com/developmenta...

Opinion | Science Suffers With Trump’s Funding Freeze America’s scientific enterprise demands reliable stewardship, not destabilizing political intervention.

My father-in-law, Jack Strominger, and I wrote a letter to the @wsj.com editor about the current threats to science due to Trump's funding freeze. Please repost! www.wsj.com/opinion/scie...

a person is holding a red object in their hand . ALT: a person is holding a red object in their hand .

ATTENTION

I am hearing from several sources that "NIH" sent out termination notices for most or all "diversity" awards yesterday to coincide with the new Notice.

If you were affected by this and are willing to share, please DM me or reach me on Signal (jeremymberg.78)

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Niemi lab and @washubbsb.bsky.social graduate student Youmian Yan gave a fantastic presentation on her work at the @asbmb.bsky.social meeting in Chicago! #ProudPI (photo credit to @kerikozul.bsky.social)

I'm excited to present my work on the deorphanization of atypical lipid catabolic enzymes at #ASBMB25 on Monday April 14th. Please come to W179 to hear my flash-talk at 9:30AM and hang out with me at poster #350! #lipidtime

If you're at #ASBMB25, head over to Eddie's poster to hear about his cool work on lipid catabolic enzymes!