iiinova — where your digital self keeps evolving

Kyle Cottrell @kylecottrell.bsky.social · 24/05/2026

Switch to natives and you get beautiful blooms and pollinators.

Kyle Cottrell @kylecottrell.bsky.social · 16/05/2026

This week the lab said goodbye to three undergraduate researchers. Estelle was the first person to join the lab. Renee and Madison joined not long after. Each have made important contributions leading to authorships. They are now off to dental, medical and graduate school! We will miss them greatly.

Renee, Madison and Estelle with their carved pumpkins.

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Kyle Cottrell @kylecottrell.bsky.social · 25/12/2025

Per tradition, the house has been built. Decorations tomorrow!

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Kyle Cottrell @kylecottrell.bsky.social · 27/11/2025

New addition this year was homemade cranberry sauce. Don't know why I waited this long to do that on.

Thanksgiving dinner, turkey, sweet potatoes, mashed potatoes, stuffing, cranberry sauce, rolls, gravy

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Kyle Cottrell @kylecottrell.bsky.social · 08/09/2025

Patience was rewarded. Wonderfully set and no soggy bottom.

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Kyle Cottrell @kylecottrell.bsky.social · 07/09/2025

What to do while you wait for the apple pie to cool? Eat the mini pie you made with the extra pastry, of course. This hack brought to you by my grandma.

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Kyle Cottrell @kylecottrell.bsky.social · 29/08/2025

The fall bloomers are starting to make an appearance! Skip the mums, plant asters!

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Kyle Cottrell @kylecottrell.bsky.social · 25/08/2025

Anyone in the West Lafayette area have an explanation for why they closed the right lane of River Road here? It's closed for maybe 200 ft. I think that they did this either to intentionally make traffic worse or to further aggravate the businesses that didn't sell their land.

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Kyle Cottrell @kylecottrell.bsky.social · 17/08/2025

Our tomatillos finally started producing!

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Kyle Cottrell @kylecottrell.bsky.social · 13/08/2025

Finally, we evaluated A-to-I editing both in cells treated with ZYS-1 or in vitro. We assessed three different A-to-I edit sites in four cell lines. With only one exception, ZYS-1 treatment did not reduce A-to-I editing in cells. We observed the same in vitro with purified ADAR1 and 5-HT2C RNA. 6/n

Analysis of A-to-I editing for a site within BPNT1 in cells treated with ZYS-1 or untreated.

Analysis of A-to-I editing in an in vitro editing assay treated with ZYS-1 or untreated.

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Kyle Cottrell @kylecottrell.bsky.social · 13/08/2025

We next asked if ZYS-1 could phenocopy ADAR1 depletion. Depletion of ADAR1 in ADAR1-dependent cell lines by knockout or knockdown causes activation of PKR and induction of interferon stimulated genes. ZYS-1 treatment generally did neither in the cell lines that we evaluated. 5/n

Immunoblots for P-PKR, PKR, ADAR1 and loading controls in two ADAR1-dependent cell lines with or without ZYS-1 treatment.

qPCR analysis of interferon stimulated gene expression.

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Kyle Cottrell @kylecottrell.bsky.social · 13/08/2025

We found that ZYS-1 killed ADAR1-dependent (those that die upon ADAR1 depletion) and ADAR1-independent cells with very similar EC50s. ZYS-1 also killed ADAR1 knockout cells as well as WT cells. 4/n

Dose response curve for the effect of ZYS-1 on cell viability.

Immunoblot confirming ADAR1 knockout. Dose response curve for the effect of ZYS-1 on cell viability in WT and ADAR1-KO cells.

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Kyle Cottrell @kylecottrell.bsky.social · 25/07/2025

A moment of beauty in the garden provides a brief distraction from the slow death of science in this country.

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Kyle Cottrell @kylecottrell.bsky.social · 23/07/2025

This isn't even close to the historical norm.

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Kyle Cottrell @kylecottrell.bsky.social · 02/06/2025

I treated the lab to a trip to the San Diego Zoo to celebrate our first preprint and for the members attending their first conference, surviving #RNA25. While the zoo is famous for the pandas, the koalas were my favorite!

Cottrell Lab in front of a panda sign at San Diego Zoo.

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Kyle Cottrell @kylecottrell.bsky.social · 29/05/2025

So, we found that PACT suppresses PKR activation through dsRNA binding and dimerization, and is partially redundant with ADAR1 in some cells. Why is this important? PACT is essential in many TNBC cell lines. It is overexpressed in TNBC and so is PKR (which is a good marker for PACT-dependency). 12/n

Graph of PACT dependency score in BRCA subtypes

Correlation between PACT dependency score and PKR protein abundance

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Kyle Cottrell @kylecottrell.bsky.social · 29/05/2025

Interestingly (for the ADAR1 aficionados at least) we found that overexpression of both ADAR1 isoforms partially rescued PKR activation and cell death. This is something we really want to study further. 11/n

Multiple figures showing that overexpression of ADAR1 isoforms partially rescued PACT depletion phenotypes.

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Kyle Cottrell @kylecottrell.bsky.social · 29/05/2025

We tested this by depleting both PACT and ADAR1 - which caused robust activation of PKR. Indicating that PACT and ADAR1 function redundantly (in some cells) to inhibit PKR. To further evaluate this, we asked if overexpression of ADAR1 isoforms could rescue the phenotypes of PACT depletion. 10/n

Immunoblot indicating activation of PKR in PACT and ADAR1 depleted cells

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Kyle Cottrell @kylecottrell.bsky.social · 29/05/2025

We used a series of knockout-rescue experiments to evaluate how PACT prevents PKR activation. These experiments revealed that dsRNA binding and dimerization of PACT is required to suppress PKR activation. The dimerization requirement is important - keep reading. 8/n

Multiple panels showing that dsRNA binding is required for inhibition of PKR by PACT.

Multiple panels showing that dimerization is required for inhibition of PKR by PACT

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Kyle Cottrell @kylecottrell.bsky.social · 29/05/2025

We did, however, observe activation of two pathways known to be activated by PKR: the integrated stress response (ISR) and NF-kB. Through a double-KO experiment we found that activation of both pathways (and cell death) in PACT-KO cells was dependent on PKR. 7/n

Dot plot of GSEA results for RNA-seq from PACT depleted or control cells

Multiple panels showing that PKR is required for PACT depletion phenotypes

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Kyle Cottrell @kylecottrell.bsky.social · 29/05/2025

Instead, we found the exact opposite. When we depleted PACT in PACT-dependent cells we observed robust activation of PKR and cell death. The same phenotypes were not observed in PACT-independent cell lines. Markers for activation of other dsRNA sensors were unchanged. 6/n

Immunoblots indicating PKR activation in PACT depleted cells

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Kyle Cottrell @kylecottrell.bsky.social · 29/05/2025

PACT is a dsRNA binding protein (dsRBP), that like ADAR1 binds with dsRNA via dsRNA binding domains (dsRBD) - and has no enzymatic domains. PACT was originally identified as an activator of PKR, but we found no evidence that PACT overexpression caused PKR activation. 5/n

Immunoblot indicating that PACT overexpressing doesn't cause PKR activation.

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Kyle Cottrell @kylecottrell.bsky.social · 29/05/2025

This project started by analysis of public DepMap data. As a postdoc studying ADAR1, I noticed that cellular sensitivity to ADAR1 loss (ADAR1-dependency) correlates with PACT-dependency. I didn't have the time or resources to study this further then, but that changed when I started my own lab. 2/n

Volcano plot of Pearson correlation statistics for pairwise comparisons of gene dependency scores with ADAR1 dependency score

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Kyle Cottrell @kylecottrell.bsky.social · 27/05/2025

The Cottrell Lab (minus the undergrads) is on our way to RNA25!

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Kyle Cottrell @kylecottrell.bsky.social · 18/05/2025

If you plant it, they will come.

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Kyle Cottrell @kylecottrell.bsky.social · 11/05/2025

Mother's Day Strawberry Shortcakes and flowers from our garden.

Bouquet of cut flowers, lilac, iris bluebells

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Kyle Cottrell @kylecottrell.bsky.social · 01/05/2025

The dynasty continues. Our third straight IM championship!

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Kyle Cottrell @kylecottrell.bsky.social · 31/03/2025

The Cottrell lab is in Indy for Pink Out the Statehouse. @cancer-inst-purdue.bsky.social www.hoosierbcadvocates.com/registration...

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Kyle Cottrell @kylecottrell.bsky.social · 30/11/2024

Last baked good for a while. Thanksgiving leftover pie. Bottom layer of stuffing (to absorb moisture and because it is fantastic), top is turkey, onion, celery, carrots, edamame, a little half&half, homemade turkey stock. All wrapped in a homemade crust and topped with turkey gravy. 11/10

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Kyle Cottrell @kylecottrell.bsky.social · 29/11/2024

I should probably eat a vegetable later.

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Kyle Cottrell @kylecottrell.bsky.social · 29/11/2024

We decided on pretzels for the Great British Baking Show finale! The pretzel dogs are still in the oven, along with soon to be cinnamon sugar bites.

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Kyle Cottrell @kylecottrell.bsky.social · 28/11/2024

Turkey is fine, and so is stuffing and sweet potatoes. But let's be honest, the real star of Thanksgiving dinner is the homemade roll!

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Kyle Cottrell @kylecottrell.bsky.social · 27/11/2024

It's the day before Thanksgiving, which means pumpkin pie baking. Turned out pretty well!

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Kyle Cottrell @kylecottrell.bsky.social · 14/11/2024

Tomorrow, we are wrapping up our module on antibiotics. Which means I get to explain the mechanism of action of puromycin! Seriously, if you don't know how puro works you should look it up.

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Kyle Cottrell @kylecottrell.bsky.social · 28/09/2023

Last day of the first rotation tomorrow. Reason enough to make peanut brittle for the lab.

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Kyle Cottrell @kylecottrell.bsky.social · 18/09/2023

Gotta love a nice, crisp, unambiguous western blot.

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