Martin Borch Jensen Profile picture
Jul 1, 2020 8 tweets 8 min read Read on X
Time to catch up on some #Senescence papers, starting with beautiful work by @corina_amor_MD, Judith Freucht & @JosefLeibold. They used #CART #CellTherapy to clear #Senescent cells, and you'll never guess what happened next! nature.com/articles/s4158…
Just kidding, you guessed it: disease model mice got better. Props to the authors for A) inducing #Senescence in 3 different ways, B) using 2 models of #NASH/liver #Fibrosis, and C) validating their senescence observations in human samples of #Cancer and #Atherosclerosis.
The linchpin of the paper was identifying a specific membrane marker on #Senescent cells, uPAR. They used bulk #Transcriptomics to identify candidates, then narrowed down with #Proteomic data. Go #Omics!
They didn't explore whether uPAR is causative for the #Senescent phenotype.
What's the context for this #CellTherapy?
As a core #AgingPathway, #Senescence is implicated in >1 #DiseasesOfAging, most of them untreatable. #Senolytics have 3 options: 1st drug for a big unmet need / a drug that could treat multiple diseases / treat #Aging to PREVENT disease.
Companies like @UnityBiotech are racing #SmallMolecule #Senolytics to market, aiming at goal 1 and maybe 2. But early compounds could have side effects precluding systemic treatment.
#CellTherapy has cost/scaling concerns, but could feasibly be imagined to achieve goals 2 and 3.
Either way, you would want a #Senolytic with a short-ish half-time, and redose. #Senescent cells are already known to function in regeneration, and other functions may still be discovered. And this applies equally for specific targets like uPAR, which may not be fully specific.
Main caveat for the paper is that it's all done in young animals. This is a POC paper and I don't fault the authors, but everything will be harder in realistic, aged models (let alone humans). And that's where you most need the therapy to work.
E.g. one experiment needed immunodeficient mice bc "normal mice cleared all #Senescent cells naturally". So will the #CellTherapy still work with an #Aged, dysfunctional immune system? For #DiseasesOfAging, it's both difficult and critical to make drugs work in that environment.

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More from @MartinBJensen

Mar 31
I'm struggling to wrap my head around the new Weissman lab myHSC depletion paper:
The first authors don't seem to be on twitter but hoping I can crowdsource a fun discussion. @dbgoodman @ImmunoFever @Jeff_Mold @Satpathology @CalebLareau...nature.com/articles/s4158…
The premise of the paper is that immune function declines with age in part because a haematopoetic stem cell (HSC) population skewed towards myeloid lineage increases in prevalence, and that targeting this population with antibodies can restore function. Cool idea!
❓1⃣: How well defined are myHSCs?
Here myHSC seems to be defined as CD150 high, based mainly on Beerman 2010 .
But looking at Figure 3, CD150 expression is a continuous distribution. Is this a clear cell population with somewhat understood behavior? pnas.org/doi/full/10.10…
Image
Read 11 tweets
Jul 5, 2022
If you want to build a career in biotech, should you get a PhD after college or join a company directly (as a Research Associate/RA, usually)?
There's no single answer, but I have the conversation often enough that I thought I'd share some pros/cons... (1/n)
First, see this thread about different types of biopharma companies. For reasons I'll get into, I think early stage (probably founder led) biotech is your best bet unless you still want to do PhD later.
(PS if you want to be a professor, it's 💯 PhD) 2/n
PhD will give you more options.
Some companies (incl. @GordianBio) will help you grow from RA to Scientist role (and beyond). But many, esp larger, companies have a glass ceiling if you don't have a PhD. Even if you pick one w/o glass ceiling, you'll be worse off it if fails. 3/n
Read 13 tweets
Jul 3, 2022
All these points resonate, for early stage biotech at least. @erlichya touches on this, but I think worth separating "industry" into different clusters that will feel quite different to someone coming from academia (still oversimplified, of course):
Pharma (eg Pfizer) vs biotech:
You wear fewer hats, see less of the company but company as a whole spans wider range of expertise, fewer changes in direction, often higher income but no chance of getting rich. Both have job insecurity: pharma doesn't go die but programs do.
Clinical vs R&D stage biotech:
Clinical may still have R&D but it's no longer the biggest driver of success vs failure. Assay validation/rigor > assay development/invention. Clinical can feel more like pharma, but with more urgency/stakes: one program = life or death of co.
Read 7 tweets
Jan 24, 2022
#SciTwitter After a lot of research and asking around, I'm making the lab equipment recommendations 🧵 I wish I'd had 2 months ago. RT/share with a #newPI or startup 🔬⚗️🛒
Note, much of the equipment hasn't arrived yet, will add comments after actual use.
-80 #freezer
Two clear winners: PHC (@panasonic) and Stirling Ultracold. Both low energy, quiet, reliable. We went with PHC because I know those to last many years, and slightly cheaper.
Thanks @MarcoJost_ @letUbeU @aryelipman #MBCBiolabs
-20 #freezer
Less clear, many viable options. We ended up getting a split of PHC MDF -30 (recommended as quieter) and much cheaper Corepoint Scientific/@VWR, will see which we prefer. Thermo hasn't failed #MBCbiolabs, but $$$ and several people said poor customer support.
Read 14 tweets
Jan 5, 2022
Something is changing about how scientific research is funded.

@Jasonmmast @endpts covers a growing set of science funding experiments: endpts.com/inside-the-mul…
These include high-throughput grants (e.g. #Fast, #Impetus), new institutes (@ArcadiaScience, @AltosLabs, @arcinstitute... I guess A is for new beginnings?), and new structures like 'nonprofit startups' (@Convergent_FROs) & @newscienceorg.
As with all experiments, I expect that some of these will disappear and that others will be a central part of science in ten years.
But them happening at all is enough to renew a conversation about how science is funded and conducted.
Read 9 tweets
Dec 27, 2021
💸 98 Longevity Impetus Grants were awarded in 2021, thanks to generous donations from @juanbenet @jamesfickel @VitalikButerin @JedMcCaleb @KarlPfleger @FEhrsam and 1 anonymous donor.
I'll summarize outcomes in this thread, awardees listed in prior one:
🦸🏽 While I've been doing most of the tweeting, the Longevity Apprentices @LNuzhna @kush__sharma @edmarferreira & Tara Mei are the real heroes for running the operations.
This has been a great Apprenticeship project, merging action and exposure to research
martinborchjensen.com/apprenticeship
🚅 The review + awards process was fairly smooth, thanks in part to @kush__sharma's custom reviewer UI. Several reviewers told us unprompted that it was their best review experience ever; the UI took 2 wks to make, so there's low hanging fruit for other agencies in that area.
Read 13 tweets

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