Lightnews — Scholar-powered news

Reposted by Kyle Cottrell

Purdue RNA Club @purduernaclub.bsky.social · 2d

RNA Club returns on Friday with Iman Mevaa from the @kasinskilab.bsky.social presenting a talk titled Targeted Delivery of Tumor-Suppressive miR-34a for Osteosarcoma Treatment.

We will meet in ABE B061 at 3:30 on October 10.

3 2

Kyle Cottrell @kylecottrell.bsky.social · 3d

My first trip out of the Purdue Airport went... well, it didn't. I ended up on the shuttle to ORD anyway. It could be great to fly out of LAF, but there probably needs to be more volume to make it reliable.

1

Kyle Cottrell @kylecottrell.bsky.social · 13d

Important aster update!

2

Kyle Cottrell @kylecottrell.bsky.social · 14d

How are we supposed to advise undergraduates interested in applying to graduate school soon? They are scared that their options will be limited. They don't know if it is better to rush to get in or wait until things maybe get better. They don't have as many options for post-bacc programs. It's rough

Kyle Cottrell @kylecottrell.bsky.social · 20d

Here is the post thread describing the work. bsky.app/profile/kyle...

Kyle Cottrell @kylecottrell.bsky.social · Aug 13

Here is the post thread I promised: We have been interested in ADAR1 as a therapeutic target for triple-negative breast cancer for a while. That project was supported by the NIH before Trump terminated it, but that is another story. While ADAR1 is a promising target - there aren't any inhibitors 1/n

Kyle Cottrell @kylecottrell.bsky.social · Aug 9

Our second preprint is out today! Post thread to come later.

1

Kyle Cottrell @kylecottrell.bsky.social · 20d

This preprint was accepted @rnajournal.bsky.social! It is now online ahead of print! @cancer-inst-purdue.bsky.social @purduernaclub.bsky.social rnajournal.cshlp.org/content/earl...

1 2 6

Kyle Cottrell @kylecottrell.bsky.social · Sep 8

Patience was rewarded. Wonderfully set and no soggy bottom.

Kyle Cottrell @kylecottrell.bsky.social · Sep 6

The mini pie in this case is technically a galette - with strawberry jam.

1

Kyle Cottrell @kylecottrell.bsky.social · Sep 6

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.

1 4

Kyle Cottrell @kylecottrell.bsky.social · Aug 29

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

2

Reposted by Kyle Cottrell

Purdue RNA Club @purduernaclub.bsky.social · Aug 26

Welcome to the bsky account for the Purdue RNA Club! Our meeting dates for Fall 2025 are September 12, October 10, November 14, and December 5.

1 4 7

Kyle Cottrell @kylecottrell.bsky.social · Aug 25

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.

Kyle Cottrell @kylecottrell.bsky.social · Aug 18

I might need to dial back the jalapeños for the next batch. 🔥🔥

Kyle Cottrell @kylecottrell.bsky.social · Aug 17

Our tomatillos finally started producing!

1

Kyle Cottrell @kylecottrell.bsky.social · Aug 17

Our tomatillos finally started producing!

3

Kyle Cottrell @kylecottrell.bsky.social · Aug 14

This is my first research article as sole corresponding author and the first research article from the Cottrell lab. I'm very happy that it ended up at RNA. This is my first time publishing in RNA and this was by far my best review experience to date. Huge thanks to editor and reviewers!

3

Kyle Cottrell @kylecottrell.bsky.social · Aug 14

This manuscript was accepted @rnajournal.bsky.social and is online ahead of publication now! Congratulations to first author Addison Young and all the co-authors (for several this is their first publication). @cancer-inst-purdue.bsky.social 1/2 rnajournal.cshlp.org/content/earl...

1 1 6

Kyle Cottrell @kylecottrell.bsky.social · Aug 13

The other authors on this preprint are both undergraduates in the lab. Estelle Gardner performed the in vitro A-to-I editing assay, and is responsible for getting this assay up and running in the lab. Renee Chua helped with the A-to-I editing analyses. 8/8

Kyle Cottrell @kylecottrell.bsky.social · Aug 13

In the end, our data do not support ZYS-1 as an ADAR1 inhibitor. Our findings are also consistent with those reported in another preprint www.biorxiv.org/content/10.1.... This is the first, first author manuscript preprint from graduate student Cassandra Smoak - who joined the lab this spring 7/n

Re: Concerns Regarding the Validation of ZYS-1 as a Bona Fide ADAR1 Inhibitor

Wang et al. in Nature Cancer report ZYS-1 as an ADAR1 inhibitor and present biochemical and cellular evidence to support ZYS-1’s direct interaction with and inhibition of ADAR1, including enzymatic as...

www.biorxiv.org

1 1

Kyle Cottrell @kylecottrell.bsky.social · Aug 13

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.

1

Kyle Cottrell @kylecottrell.bsky.social · Aug 13

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.

1 1

Kyle Cottrell @kylecottrell.bsky.social · Aug 13

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.

1

Kyle Cottrell @kylecottrell.bsky.social · Aug 13

Recently, ZYS-1 was reported to inhibit ADAR1 www.nature.com/articles/s43.... Given our past experience evaluating putative ADAR1 inhibitors, we decided to put ZYS-1 through a series of tests. First, we asked if ZYS-1 is more cytotoxic to ADAR1-dependent vs ADAR1-independent cells. 3/n

Targeting ADAR1 with a small molecule for the treatment of prostate cancer - Nature Cancer

Yang and colleagues present a small-molecule inhibitor for ADAR1 and show that its use is therapeutically beneficial in the context of prostate cancer.

www.nature.com

1

Kyle Cottrell @kylecottrell.bsky.social · Aug 13

ADAR1 carries out A-to-I editing of RNA. Its substrate is dsRNA. Previous groups have reported adenosine analogues as a ADAR1 inhibitors, but we have found those not to be selective inhibitors of ADAR1 aacrjournals.org/cancerrescom... 2/n

www.nature.com

1

Kyle Cottrell @kylecottrell.bsky.social · Aug 13

Here is the post thread I promised: We have been interested in ADAR1 as a therapeutic target for triple-negative breast cancer for a while. That project was supported by the NIH before Trump terminated it, but that is another story. While ADAR1 is a promising target - there aren't any inhibitors 1/n

Kyle Cottrell @kylecottrell.bsky.social · Aug 9

Our second preprint is out today! Post thread to come later.

bioRxivpreprint @biorxivpreprint.bsky.social · Aug 9

ZYS-1 is not an ADAR1 inhibitor https://www.biorxiv.org/content/10.1101/2025.08.08.669362v1

1 1

Kyle Cottrell @kylecottrell.bsky.social · Aug 9

Our second preprint is out today! Post thread to come later.

bioRxivpreprint @biorxivpreprint.bsky.social · Aug 9

ZYS-1 is not an ADAR1 inhibitor https://www.biorxiv.org/content/10.1101/2025.08.08.669362v1

1 4