Kyle Cottrell
@kylecottrell.bsky.social
Father | Assistant Professor @PurdueBiochem (RNA editing and regulation) | Postdoc & PhD @WUSTL | MS & BS @MissouriState | #firstgen #NewPI #NIHMOSAIC K99/R00 (posts and comments are my own and do not reflect my employer)
Almost made it to Thanksgiving.
November 23, 2025 at 10:32 PM
Almost made it to Thanksgiving.
Important aster update!
September 26, 2025 at 3:21 AM
Important aster update!
Patience was rewarded. Wonderfully set and no soggy bottom.
September 8, 2025 at 3:30 PM
Patience was rewarded. Wonderfully set and no soggy bottom.
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.
September 6, 2025 at 11:46 PM
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.
The fall bloomers are starting to make an appearance! Skip the mums, plant asters!
August 29, 2025 at 12:13 AM
The fall bloomers are starting to make an appearance! Skip the mums, plant asters!
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.
August 25, 2025 at 1:22 AM
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.
Our tomatillos finally started producing!
August 17, 2025 at 6:18 PM
Our tomatillos finally started producing!
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
August 13, 2025 at 4:35 PM
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
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
August 13, 2025 at 4:35 PM
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
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
August 13, 2025 at 4:35 PM
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
A moment of beauty in the garden provides a brief distraction from the slow death of science in this country.
July 25, 2025 at 9:22 PM
A moment of beauty in the garden provides a brief distraction from the slow death of science in this country.
This isn't even close to the historical norm.
July 23, 2025 at 10:34 PM
This isn't even close to the historical norm.
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!
June 1, 2025 at 11:32 PM
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!
Purdue Biochemistry and @cancer-inst-purdue.bsky.social at #RNA25
May 29, 2025 at 10:07 PM
Purdue Biochemistry and @cancer-inst-purdue.bsky.social at #RNA25
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
May 29, 2025 at 5:14 PM
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
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
May 29, 2025 at 5:14 PM
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
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
May 29, 2025 at 5:14 PM
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
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
May 29, 2025 at 5:14 PM
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
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
May 29, 2025 at 5:14 PM
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
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
May 29, 2025 at 5:14 PM
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
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
May 29, 2025 at 5:14 PM
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
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
May 29, 2025 at 5:14 PM
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
The Cottrell Lab (minus the undergrads) is on our way to RNA25!
May 27, 2025 at 1:24 PM
The Cottrell Lab (minus the undergrads) is on our way to RNA25!
If you plant it, they will come.
May 18, 2025 at 5:15 PM
If you plant it, they will come.