Mike Lee
@theleelab.bsky.social
A laboratory of Systems Pharmacology at UMass Medical School. We study cancer therapies, and aim to understand how they activate cell death and how to make this work better.
https://www.umassmed.edu/Lee-Lab
https://www.umassmed.edu/Lee-Lab
A nice Q&A with Nick Harper about the discovery of PDAR, and his road to becoming a scientist @umasschan.bsky.social
www.umassmed.edu/dsb/dsb-comm...
www.umassmed.edu/dsb/dsb-comm...
August 22, 2025 at 1:40 PM
A nice Q&A with Nick Harper about the discovery of PDAR, and his road to becoming a scientist @umasschan.bsky.social
www.umassmed.edu/dsb/dsb-comm...
www.umassmed.edu/dsb/dsb-comm...
We call this pathway the Pol II Degradation-dependent Apoptotic Response (PDAR).
Our study highlights 3 major surprises about PDAR:
2/n 🧪
Our study highlights 3 major surprises about PDAR:
2/n 🧪
August 15, 2025 at 6:37 PM
We call this pathway the Pol II Degradation-dependent Apoptotic Response (PDAR).
Our study highlights 3 major surprises about PDAR:
2/n 🧪
Our study highlights 3 major surprises about PDAR:
2/n 🧪
Things have been challenging over these last few months, but we also had a lot to celebrate...
Tiana and Mika joining the lab 🎉,
Kelly passing her QE 🎉,
Gavin publishing a paper and submitting another 🎉,
Megan publishing a paper 🎉,
Nick getting excellent reviews 🎉
...so we did a paint nite.
Tiana and Mika joining the lab 🎉,
Kelly passing her QE 🎉,
Gavin publishing a paper and submitting another 🎉,
Megan publishing a paper 🎉,
Nick getting excellent reviews 🎉
...so we did a paint nite.
June 23, 2025 at 3:18 PM
Things have been challenging over these last few months, but we also had a lot to celebrate...
Tiana and Mika joining the lab 🎉,
Kelly passing her QE 🎉,
Gavin publishing a paper and submitting another 🎉,
Megan publishing a paper 🎉,
Nick getting excellent reviews 🎉
...so we did a paint nite.
Tiana and Mika joining the lab 🎉,
Kelly passing her QE 🎉,
Gavin publishing a paper and submitting another 🎉,
Megan publishing a paper 🎉,
Nick getting excellent reviews 🎉
...so we did a paint nite.
The answer is about analytical resolution!!! The way we measure drug responses makes drug-induced growth rates and death rates very clear. More conventional approaches just can't see these distinctions clearly, masking this crazy phenotype. (8/end)
December 13, 2024 at 2:29 PM
The answer is about analytical resolution!!! The way we measure drug responses makes drug-induced growth rates and death rates very clear. More conventional approaches just can't see these distinctions clearly, masking this crazy phenotype. (8/end)
We identified many clinically used drugs that owe their lethality to a PDAR-dependent cell death. Many of these are not conventionally thought of as transcriptional inhibitors! (6/n)
December 13, 2024 at 2:27 PM
We identified many clinically used drugs that owe their lethality to a PDAR-dependent cell death. Many of these are not conventionally thought of as transcriptional inhibitors! (6/n)
We did a genetic screen to identify regulators of this death response... We call this response PDAR: The Pol II Degradation-dependent Apoptotic Response. (5/n)
December 13, 2024 at 2:26 PM
We did a genetic screen to identify regulators of this death response... We call this response PDAR: The Pol II Degradation-dependent Apoptotic Response. (5/n)
It's challenging to uncouple Pol II expression and Pol II activity (Pol II activity creates Pol II expression, & vice versa) but we managed! We did many things, but the most notable is that we suppressed lethality caused by loss of Pol II by giving cells a non-functional form of Pol II! (4/n)
December 13, 2024 at 2:23 PM
It's challenging to uncouple Pol II expression and Pol II activity (Pol II activity creates Pol II expression, & vice versa) but we managed! We did many things, but the most notable is that we suppressed lethality caused by loss of Pol II by giving cells a non-functional form of Pol II! (4/n)
We spent a lot of time trying to rationalize this through the decay rates of certain transcripts/proteins, but it just never worked. The big 'ah-ha' was when we noticed that variation in death kinetics (across drugs) was perfectly coupled to variation in the loss of the inactive form of Pol II (3/n)
December 13, 2024 at 2:21 PM
We spent a lot of time trying to rationalize this through the decay rates of certain transcripts/proteins, but it just never worked. The big 'ah-ha' was when we noticed that variation in death kinetics (across drugs) was perfectly coupled to variation in the loss of the inactive form of Pol II (3/n)
we first noticed that death following loss of Pol II is exclusively apoptotic. This is surprising, considering that there are many other ways for cells to "waste away" in the absence of gene expression... in spite of this, cells that can't do apoptosis just sit there. pretty happily in fact (2/n)
December 13, 2024 at 2:20 PM
we first noticed that death following loss of Pol II is exclusively apoptotic. This is surprising, considering that there are many other ways for cells to "waste away" in the absence of gene expression... in spite of this, cells that can't do apoptosis just sit there. pretty happily in fact (2/n)