pitarresilab.bsky.social
Jason R. Pitarresi PhD
Father. Assistant Professor @UMassChan Medical School.
Studying pancreatic cancer, cellular plasticity/metastasis, and tumor-host interactions.
www.PitarresiLab.com
44 posts
613 followers
797 following
Prolific Poster
Conversation Starter
comment in response to
post
Immensely grateful to all collaborators from the Guertin, @marcus-ruscetti.bsky.social, @game-of-chroms.bsky.social, Zhu, Kremer, Czech, Guilherme, and Hollingsworth labs. you all have made this journey an amazing one.🙏
comment in response to
post
Most importantly, this paper only came together because of the fantastic community of collaborators we have built over the years.
Really proud of my team led by @nikitab.bsky.social with critical support from Yamini Ogoti, @jessicapeura.bsky.social, and @calvinjohnsonio.bsky.social
...🧵
comment in response to
post
To wrap this story up, we treated KPCY animals with a monoclonal neutralizing antibody against PTHrP (🙏 Richard Kremer), which was able to block wasting and restore DNL. We are hoping this will be a new therapeutic option for patients suffering from cancer cachexia in the near future
...🧵
comment in response to
post
This is where we relied on our adipose tissue expert collaborators (Dave Guertin, Mike Czech, Adilson Guilherme labs), who helped us delete Fasn, a key enzyme in the DNL pathway, in adipocytes. When we injected a non-cachectic cell line into these mice, we found that it became cachectic!
...🧵
comment in response to
post
To figure out how PTHrP mediates adipose tissue wasting, we performed RNA-seq on cachectic iWAT and found the usual players being upregulated (TNF, IL6, etc.), but were surprised to also see a dramatic downregulation of de novo lipogenesis (DNL) in the adipose of cachectic mice
...🧵
comment in response to
post
We knew that adipocytes have high levels of the PTHrP receptor, PTH1R. We deleted Pth1r in adipose and injected our highly cachectic PTHrP-OE cell line. This not only blocked adipose tissue wasting, but also muscle wasting, suggesting that adipose wasting may fuel muscle wasting in this model
...🧵
comment in response to
post
We weren’t sure if PTHrP alone was driving this, so we injected WT animals with recombinant PTHrP and, to our surprise, they started to lose their adipose tissue. This is where things started to get really interesting
…🧵
comment in response to
post
Next, we wanted to establish that PTHrP is sufficient for wasting, so we overexpressed Pthlh in a non-cachectic KPC line with low endogenous Pthlh. This effectively converted the non-cachectic cell line into a cachectic one, which dramatically reduced overall survival
...🧵
comment in response to
post
We saw big differences in adipose and muscle wasting phenotypes in Pthlh-deleted KPCY mice and noted that cachectic PDAC patients had higher tumor cell PTHrP expression in their primary tumors
...🧵
comment in response to
post
It is known clinically that PDAC patients with high PTHrP serum are more cachectic, so we dug a little deeper and found that Pthlh-deleted KPCY mice were resistant to PDAC-associated weight loss. So, it looks like PTHrP is necessary for cachectic wasting in KPC mice
...🧵
comment in response to
post
It started a few years ago when we had this exciting data showing that Pthlh (the gene encoding PTHrP) deletion in KPCY mice dramatically extended survival. We attributed this to a decrease in metastasis in a prior paper, but upon closer examination, we found they were also less cachectic
...🧵
comment in response to
post
No name or signature. Based on others responding above, it looks like this is a stock response going out
comment in response to
post
Re-expression of the EMT transcription factor, Snail, was sufficient to restore metastatic competency in MCU-null tumor cells.
This work highlights the potential for targeting mitochondrial Ca2+ signaling in pancreatic cancer therapy.
comment in response to
post
In this work, we show that deletion of the mitochondrial calcium uniporter, MCU (which enables mitochondrial Ca2+ uptake), reduces metastatic capability in PDAC by blocking epithelial to mesenchymal transition (EMT), which is thought to contribute to metastasis.
comment in response to
post
It was a truly collaborative effort lead by Jillian Weissenrieder, who is currently on the job market and moving to the Seattle area soon! Excited to see what she will do in the near future!!
Reach out to @skyeweisse.bsky.social if you know of any opening (academia or industry)
comment in response to
post
Will post more details when in comes online, but here's the original biorxiv for now:
www.biorxiv.org/content/10.1...
comment in response to
post
I have confirmation from several sources now that all T32s, many F30s and F31s, and most or all Center awards (P30, P50) have been terminated at Columbia.
This is quite damaging to research and to individuals.
This is pure terrorism and cannot be legal. But litigation will take time...
comment in response to
post
Thank you! Others have also recommended similar cores and services in my DMs, so now I have lots of options!
comment in response to
post
It's mostly just tightening up our response letter and finalizing some discussion at this point. All of the experiments are done and turned out 👍👍