Alex Federation
@afederation.bsky.social
Co-founder, CEO of Talus Bio.
Drugging "undruggable" transcription factors with proteomics #chembio.
Scientist, mountain runner, new dad.
https://readout.substack.com
Drugging "undruggable" transcription factors with proteomics #chembio.
Scientist, mountain runner, new dad.
https://readout.substack.com
I just ran the first n=1 dynamic regulome experiment. On myself.
A 72-hour fast where we tracked all 4,000+ components of the genome regulatory 'software' to see how they respond
And over 30% changed, most never mentioned in fasting literature
Why does this matter?
A 72-hour fast where we tracked all 4,000+ components of the genome regulatory 'software' to see how they respond
And over 30% changed, most never mentioned in fasting literature
Why does this matter?
July 10, 2025 at 12:14 PM
I just ran the first n=1 dynamic regulome experiment. On myself.
A 72-hour fast where we tracked all 4,000+ components of the genome regulatory 'software' to see how they respond
And over 30% changed, most never mentioned in fasting literature
Why does this matter?
A 72-hour fast where we tracked all 4,000+ components of the genome regulatory 'software' to see how they respond
And over 30% changed, most never mentioned in fasting literature
Why does this matter?
Reposted by Alex Federation
The EUBIC-MS Developers Meeting 2025 in Brixen is off to a great start with keynotes by Pavel Sinitcyn, Katerina Nastou, and @willfondrie.com.
#EuBIC2025
#EuBIC2025
February 3, 2025 at 12:59 PM
The EUBIC-MS Developers Meeting 2025 in Brixen is off to a great start with keynotes by Pavel Sinitcyn, Katerina Nastou, and @willfondrie.com.
#EuBIC2025
#EuBIC2025
Reposted by Alex Federation
It’s been a tough few weeks. My 10yo daughter was diagnosed with a very rare, aggressive cancer called interdigitating dendritic cell sarcoma (IDCS). I’m reaching out to identify clinicians/patients who have encountered pediatric IDCS or other (non-LCH) dendritic or histiocytic sarcomas cases.
February 8, 2025 at 9:21 PM
It’s been a tough few weeks. My 10yo daughter was diagnosed with a very rare, aggressive cancer called interdigitating dendritic cell sarcoma (IDCS). I’m reaching out to identify clinicians/patients who have encountered pediatric IDCS or other (non-LCH) dendritic or histiocytic sarcomas cases.
Some diseases are too rare to be VC-fundable. Without grant funding, these patients get nothing—that’s unacceptable.
NIH grants fund our work on a rare cancer with no approved treatments. Every year, we pay out of pocket for a third-party audit to prove there’s no waste, no fraud—just science.
NIH grants fund our work on a rare cancer with no approved treatments. Every year, we pay out of pocket for a third-party audit to prove there’s no waste, no fraud—just science.
February 8, 2025 at 1:42 PM
Some diseases are too rare to be VC-fundable. Without grant funding, these patients get nothing—that’s unacceptable.
NIH grants fund our work on a rare cancer with no approved treatments. Every year, we pay out of pocket for a third-party audit to prove there’s no waste, no fraud—just science.
NIH grants fund our work on a rare cancer with no approved treatments. Every year, we pay out of pocket for a third-party audit to prove there’s no waste, no fraud—just science.
Does anyone know if the savings will be re-invested into more grants?
Or is this just slashing the overall budget of the NIH?
Or is this just slashing the overall budget of the NIH?
Flat 15% indirect costs across all grants (notes this will work because only 3 places - MIT, UMich, UAB - ever REFUSED a grant for lower than expected previous indirects). Impacts of this cut will presumably destroy research - current indirects are ~50%+
grants.nih.gov/grants/guide...
grants.nih.gov/grants/guide...
NOT-OD-25-068: Supplemental Guidance to the 2024 NIH Grants Policy Statement: Indirect Cost Rates
NIH Funding Opportunities and Notices in the NIH Guide for Grants and Contracts: Supplemental Guidance to the 2024 NIH Grants Policy Statement: Indirect Cost Rates NOT-OD-25-068. OD
grants.nih.gov
February 7, 2025 at 11:59 PM
Does anyone know if the savings will be re-invested into more grants?
Or is this just slashing the overall budget of the NIH?
Or is this just slashing the overall budget of the NIH?
Love to see more teams getting into the multidimensional drug screening game with DIA proteomics.
380 kinases in one assay -
pubs.acs.org/doi/10.1021/...
380 kinases in one assay -
pubs.acs.org/doi/10.1021/...
Automated High-Throughput Affinity Capture-Mass Spectrometry Platform with Data-Independent Acquisition
Affinity capture (AC) combined with mass spectrometry (MS)-based proteomics is highly utilized throughout the drug discovery pipeline to determine small-molecule target selectivity and engagement. How...
pubs.acs.org
January 28, 2025 at 1:58 PM
Love to see more teams getting into the multidimensional drug screening game with DIA proteomics.
380 kinases in one assay -
pubs.acs.org/doi/10.1021/...
380 kinases in one assay -
pubs.acs.org/doi/10.1021/...
Reposted by Alex Federation
Getting a bit tight in the hallways #teamMassSpec #proteomics
January 27, 2025 at 9:56 PM
Getting a bit tight in the hallways #teamMassSpec #proteomics
That seems... like a reasonable number? I'm surprised it's not higher, especially since a postdoc will usually double their salary going into industry
www.nature.com/articles/d41...
www.nature.com/articles/d41...
More than 40% of postdocs leave academia, study reveals
Publishing highly cited papers helps postdoctoral researchers to land a faculty job.
www.nature.com
January 27, 2025 at 3:46 PM
That seems... like a reasonable number? I'm surprised it's not higher, especially since a postdoc will usually double their salary going into industry
www.nature.com/articles/d41...
www.nature.com/articles/d41...
Cancer might be the most creative biologist - it's evolutionary "job" is to stress test every biological mechanism in our cells are see if promoted survival/fitness
Apparently tumors can tunnel into lymphocytes and dump their mutated mitochondria?
What a wild world
Apparently tumors can tunnel into lymphocytes and dump their mutated mitochondria?
What a wild world
🧬 How Cancer Poisons the Immune System
New research uncovers how tumours transfer their mitochondria to immune cells, disrupting their function and weakening the body’s defences.
Could understanding this process lead to better cancer treatments?
🔗 www.nature.com/articles/s41...
🧪 #SciComm
New research uncovers how tumours transfer their mitochondria to immune cells, disrupting their function and weakening the body’s defences.
Could understanding this process lead to better cancer treatments?
🔗 www.nature.com/articles/s41...
🧪 #SciComm
Immune evasion through mitochondrial transfer in the tumour microenvironment - Nature
Mitochondria with mutations in their DNA from cancer cells can be transferred to T cells in the tumour microenvironment, which leads to T cell dysfunction and impaired antitumour immunity.
www.nature.com
January 26, 2025 at 3:53 PM
Cancer might be the most creative biologist - it's evolutionary "job" is to stress test every biological mechanism in our cells are see if promoted survival/fitness
Apparently tumors can tunnel into lymphocytes and dump their mutated mitochondria?
What a wild world
Apparently tumors can tunnel into lymphocytes and dump their mutated mitochondria?
What a wild world
This is the perspective I was waiting for after seeing all the new transcription factor footprinting papers 👇
There has been a couple of manuscripts released regarding transcription factor footprinting - or digital genomic footprinting (DGF) as we call it. I would like to put some of the claims, results and conclusions in context, since I have worked and published on this for ~15 years. 1/n
January 25, 2025 at 11:18 PM
This is the perspective I was waiting for after seeing all the new transcription factor footprinting papers 👇
Nice discussion here - we're doing our part building the first proteomics search engine that can handle the scale needed for drug discovery
www.nautilus.bio/blog/transla...
www.nautilus.bio/blog/transla...
Translating Proteomics Episode 15: Combating the Reproducibility Crisis in Computational Proteomics
Discover new ways to improve the reproducibility of proteomic and multiomic analyses.
www.nautilus.bio
January 23, 2025 at 6:17 PM
Nice discussion here - we're doing our part building the first proteomics search engine that can handle the scale needed for drug discovery
www.nautilus.bio/blog/transla...
www.nautilus.bio/blog/transla...
I'm not sure how I missed this, but apparently there's a flash of light when the egg gets fertilized!?
Pretty wild
www.nature.com/articles/sre...
Pretty wild
www.nature.com/articles/sre...
The zinc spark is an inorganic signature of human egg activation - Scientific Reports
Scientific Reports - The zinc spark is an inorganic signature of human egg activation
www.nature.com
January 12, 2025 at 7:33 PM
I'm not sure how I missed this, but apparently there's a flash of light when the egg gets fertilized!?
Pretty wild
www.nature.com/articles/sre...
Pretty wild
www.nature.com/articles/sre...
Reposted by Alex Federation
Re-upping this reply thread from last night. Drugs don't come from nowhere, folks. And we're not ripping off the NIH, either.
I think you're describing science, IMO. Everything is atop a foundation of basic research. An example: at a previous company, I worked on a series of small-molecule inhibitors of Hormone-Sensitive Lipase, a possible target for Type II diabetes and related conditions. (1/10)
January 6, 2025 at 2:36 PM
Re-upping this reply thread from last night. Drugs don't come from nowhere, folks. And we're not ripping off the NIH, either.
Lots of really cool molecules here. The menin inhibitors are super important. No new transcription factor inhibitors, sadly. On to 2025 🚀
Very interesting to see the 50 new drugs that made it to FDA approval in 2024 in one place. A lot of really exciting small molecule chemistry with interesting functional groups, deuterations and covalent warheads. #chemsky #chembio
www.linkedin.com/posts/chrisd...
www.linkedin.com/posts/chrisd...
Chris De Savi on LinkedIn: #medicine #pharmaceuticals #healthcare | 90 comments
FDA Novel Drug Approvals 2024 #medicine
That is a wrap for 2024! And another year of relentless drug discovery!
There you have it, drug-hunting aficionados,… | 90 comments on LinkedIn
www.linkedin.com
January 3, 2025 at 2:54 PM
Lots of really cool molecules here. The menin inhibitors are super important. No new transcription factor inhibitors, sadly. On to 2025 🚀
Reposted by Alex Federation
January 2, 2025 at 3:45 AM
Don't think I've ever read something this moving about gene regulation before
For those of us who are not professional biologists, it can be daunting to hear about transcription factors, signaling pathways and non-coding RNA. But this poignant piece from @philipcball.bsky.social opened my eyes to how deep and essential these ideas truly are. nautil.us/how-life-rea...
How Life Really Works
Just as I uncovered a new way to understand life, I got news about my own.
nautil.us
December 28, 2024 at 8:00 PM
Don't think I've ever read something this moving about gene regulation before
Wow. Very impressive work with in vivo dTAG looking at KRAS G12V.
Lots more to learn with this technology, this is only the start. Congratulations Behnam and team!
Lots more to learn with this technology, this is only the start. Congratulations Behnam and team!
🧪 Ready, set, degrade!
So proud to share our work in the @jclinical-invest.bsky.social, establishing a versatile approach for creating transgenic dTAG mice to degrade oncoproteins. We showcase that KRAS G12V degradation triggers antitumor immunity in lung cancer.
Link: www.jci.org/articles/vie...
So proud to share our work in the @jclinical-invest.bsky.social, establishing a versatile approach for creating transgenic dTAG mice to degrade oncoproteins. We showcase that KRAS G12V degradation triggers antitumor immunity in lung cancer.
Link: www.jci.org/articles/vie...
December 27, 2024 at 9:25 PM
Wow. Very impressive work with in vivo dTAG looking at KRAS G12V.
Lots more to learn with this technology, this is only the start. Congratulations Behnam and team!
Lots more to learn with this technology, this is only the start. Congratulations Behnam and team!
Reposted by Alex Federation
People sometimes make fun of science that sounds stupid and random.
Meanwhile, a study of lizard saliva turned into a peptide medication, which was turned into a diabetes medication, which was turned into a GLP1 weight loss drug, that just became the first therapy every approved for … sleep apnea
Meanwhile, a study of lizard saliva turned into a peptide medication, which was turned into a diabetes medication, which was turned into a GLP1 weight loss drug, that just became the first therapy every approved for … sleep apnea
Breaking News: The FDA approved use of the weight loss drug Zepbound for a common form of sleep apnea. It is the first drug authorized to treat the disorder.
F.D.A. Approves Weight-Loss Drug to Treat Sleep Apnea
Zepbound is the first prescription drug approved specifically to treat the common condition.
www.nytimes.com
December 21, 2024 at 12:41 AM
People sometimes make fun of science that sounds stupid and random.
Meanwhile, a study of lizard saliva turned into a peptide medication, which was turned into a diabetes medication, which was turned into a GLP1 weight loss drug, that just became the first therapy every approved for … sleep apnea
Meanwhile, a study of lizard saliva turned into a peptide medication, which was turned into a diabetes medication, which was turned into a GLP1 weight loss drug, that just became the first therapy every approved for … sleep apnea
Spatial proteomics wins method of the year!
Our team at @talusbio.bsky.social isn't using IF-based spatial proteomics, TF-Scan does provide a surrogate of protein localization within the nucleus, with enough throughput to be useful for drug discovery.
www.nature.com/articles/s41...
Our team at @talusbio.bsky.social isn't using IF-based spatial proteomics, TF-Scan does provide a surrogate of protein localization within the nucleus, with enough throughput to be useful for drug discovery.
www.nature.com/articles/s41...
Method of the Year 2024: spatial proteomics - Nature Methods
Approaches for profiling the spatial proteome in tissues are the basis of atlas-scale projects that are delivering on their promise for understanding biological complexity in health and disease.
www.nature.com
December 12, 2024 at 2:11 AM
Spatial proteomics wins method of the year!
Our team at @talusbio.bsky.social isn't using IF-based spatial proteomics, TF-Scan does provide a surrogate of protein localization within the nucleus, with enough throughput to be useful for drug discovery.
www.nature.com/articles/s41...
Our team at @talusbio.bsky.social isn't using IF-based spatial proteomics, TF-Scan does provide a surrogate of protein localization within the nucleus, with enough throughput to be useful for drug discovery.
www.nature.com/articles/s41...
Reposted by Alex Federation
One of the reasons I joined @talusbio.bsky.social was @afederation.bsky.social and @lkpino.bsky.social's commitment to open science 👏
One of the first posts on our new company blog is a repost from my own blog on #OSS in #proteomics.
Check it out here:
blog.talus.bio/p/the-case-f...
One of the first posts on our new company blog is a repost from my own blog on #OSS in #proteomics.
Check it out here:
blog.talus.bio/p/the-case-f...
The Case for Open-Source Scientific Software
Papers without code are just advertisements.
blog.talus.bio
December 11, 2024 at 6:10 PM
One of the reasons I joined @talusbio.bsky.social was @afederation.bsky.social and @lkpino.bsky.social's commitment to open science 👏
One of the first posts on our new company blog is a repost from my own blog on #OSS in #proteomics.
Check it out here:
blog.talus.bio/p/the-case-f...
One of the first posts on our new company blog is a repost from my own blog on #OSS in #proteomics.
Check it out here:
blog.talus.bio/p/the-case-f...
Reposted by Alex Federation
I'm processing some DIA data using #DIANN and looking at the data using the Viewer (excellent addition!), many peptides don't look impressive (to say the least). Is it possible to be more stringent in assigning frags to precursors? #proteomics
December 8, 2024 at 11:10 AM
I'm processing some DIA data using #DIANN and looking at the data using the Viewer (excellent addition!), many peptides don't look impressive (to say the least). Is it possible to be more stringent in assigning frags to precursors? #proteomics
Really cool pipeline, excited to play around with this (someday)
I've been working to make designing regulatory DNA that exhibits desired characteristics easier for everyone. With the following series of tools, you can go from a blank slate to designed edits in ~30 minutes using only a V100. That includes file downloading and model training.
December 10, 2024 at 10:37 PM
Really cool pipeline, excited to play around with this (someday)
Where would genomics be if the BAM/SAM file format was proprietary and Bamtools/Bowtie was closed source and prohibitively expensive? That's where the proteomics field is right now. Talus Bio's @willfondrie.com and a group of industry+academia leaders share -
This was a ton of fun to write with @ypriverol.bsky.social and all of the other authors 👏
Our goal was to share a vision of #OSS #proteomics for us to build toward, and propose some ways to get there 🚀
I’m blown away by how many folks contributed and how much it evolved beyond just my voice 🙌
Our goal was to share a vision of #OSS #proteomics for us to build toward, and propose some ways to get there 🚀
I’m blown away by how many folks contributed and how much it evolved beyond just my voice 🙌
Recently, We saw a discussion on the role of open-source in proteomics. Here, experienced developers & researchers maintaining OS tools for years shared this comment to guide newcomers in the field about OS and its role in the field. 💻 #Proteomics #OpenSource chemrxiv.org/engage/chemr...
December 9, 2024 at 5:48 PM
Where would genomics be if the BAM/SAM file format was proprietary and Bamtools/Bowtie was closed source and prohibitively expensive? That's where the proteomics field is right now. Talus Bio's @willfondrie.com and a group of industry+academia leaders share -
Reposted by Alex Federation
You may have seen a recent pre-print [1] from Jain et al. with strongly worded claims against the experimental results in our DiffDock paper [2]. We initially declined to respond as we saw that this preprint contained falsehoods, misleading comparisons, seemingly deliberate omissions, ...1/n
December 8, 2024 at 9:37 PM
You may have seen a recent pre-print [1] from Jain et al. with strongly worded claims against the experimental results in our DiffDock paper [2]. We initially declined to respond as we saw that this preprint contained falsehoods, misleading comparisons, seemingly deliberate omissions, ...1/n