Neel Shah
LightNews LightNews
banner
nshahlab.bsky.social
Neel Shah
@nshahlab.bsky.social
670 followers 550 following 70 posts
Assistant Professor at Columbia Chemistry. PI of a chemical biology lab full of awesome people. Internal conflicts: Chemist or biologist? Kinase or phosphatase?

Lab website: https://shahlab.wixsite.com/home
ORCiD: 0000-0002-1186-0626
Posts Replies Media Videos
nshahlab.bsky.social
First time back in the Bay Area since I left Berkeley 7 years ago. Met some old friends after a long time and had an awesome visit at UCSF. Didn’t realize I missed this place!
Picture of the bay bridge at night.
November 22, 2025 at 5:24 PM
Reposted by Neel Shah
chembiobryan.bsky.social
Check out our newest work! This is a story on how to get selectivity in binders - both isoform and site selectivity. Read the paper or enjoy this brief Skytorial of what we did!

www.biorxiv.org/content/10.1...

1/n
PANCS-spec-Binders: A system for rapidly discovering isoform- or epitope-specific binders
Proteins that bind to a target protein of interest, termed "binders," are essential components of biological research reagents and therapeutics. Target proteins present multiple binding surfaces with ...
www.biorxiv.org
November 19, 2025 at 6:10 PM
Reposted by Neel Shah
biorxivpreprint.bsky.social
FlAsH-ID: A short peptide tag for live cell photoproximity labeling https://www.biorxiv.org/content/10.1101/2025.10.24.684417v1
October 25, 2025 at 3:18 AM
Reposted by Neel Shah
harriswang.bsky.social
📢 Our Dept. of Systems Biology at Columbia University has an open tenure-track Assistant Professor position in the broad area of quantitative biology. Come join our awesome department in NYC! Please circulate.
apply.interfolio.com/177622
Suggested deadline: 12/15/2025.
@columbiasysbio.bsky.social
November 15, 2025 at 4:02 AM
nshahlab.bsky.social
Our paper entitled, "The pathogenic E139D mutation stabilizes a non-canonical active state of the multi-domain phosphatase SHP2" is out in its final form at Protein Science. Big congrats to former grad students Anne and Jason, and former undergrad Anya!

onlinelibrary.wiley.com/doi/10.1002/...
November 13, 2025 at 8:09 PM
Reposted by Neel Shah
hansonmark.bsky.social
We wrote the Strain on scientific publishing to highlight the problems of time & trust. With a fantastic group of co-authors, we present The Drain of Scientific Publishing:

a 🧵 1/n

Drain: arxiv.org/abs/2511.04820
Strain: direct.mit.edu/qss/article/...
Oligopoly: direct.mit.edu/qss/article/...
A table showing profit margins of major publishers. A snippet of text related to this table is below. 1. The four-fold drain 1.1 Money Currently, academic publishing is dominated by profit-oriented, multinational companies for whom scientific knowledge is a commodity to be sold back to the academic community who created it. The dominant four are Elsevier, Springer Nature, Wiley and Taylor & Francis, which collectively generated over US$7.1 billion in revenue from journal publishing in 2024 alone, and over US$12 billion in profits between 2019 and 2024 (Table 1A). Their profit margins have always been over 30% in the last five years, and for the largest publisher (Elsevier) always over 37%. Against many comparators, across many sectors, scientific publishing is one of the most consistently profitable industries (Table S1). These financial arrangements make a substantial difference to science budgets. In 2024, 46% of Elsevier revenues and 53% of Taylor & Francis revenues were generated in North America, meaning that North American researchers were charged over US$2.27 billion by just two for-profit publishers. The Canadian research councils and the US National Science Foundation were allocated US$9.3 billion in that year. A figure detailing the drain on researcher time. 1. The four-fold drain 1.2 Time The number of papers published each year is growing faster than the scientific workforce, with the number of papers per researcher almost doubling between 1996 and 2022 (Figure 1A). This reflects the fact that publishers’ commercial desire to publish (sell) more material has aligned well with the competitive prestige culture in which publications help secure jobs, grants, promotions, and awards. To the extent that this growth is driven by a pressure for profit, rather than scholarly imperatives, it distorts the way researchers spend their time. The publishing system depends on unpaid reviewer labour, estimated to be over 130 million unpaid hours annually in 2020 alone (9). Researchers have complained about the demands of peer-review for decades, but the scale of the problem is now worse, with editors reporting widespread difficulties recruiting reviewers. The growth in publications involves not only the authors’ time, but that of academic editors and reviewers who are dealing with so many review demands. Even more seriously, the imperative to produce ever more articles reshapes the nature of scientific inquiry. Evidence across multiple fields shows that more papers result in ‘ossification’, not new ideas (10). It may seem paradoxical that more papers can slow progress until one considers how it affects researchers’ time. While rewards remain tied to volume, prestige, and impact of publications, researchers will be nudged away from riskier, local, interdisciplinary, and long-term work. The result is a treadmill of constant activity with limited progress whereas core scholarly practices – such as reading, reflecting and engaging with others’ contributions – is de-prioritized. What looks like productivity often masks intellectual exhaustion built on a demoralizing, narrowing scientific vision. A table of profit margins across industries. The section of text related to this table is below: 1. The four-fold drain 1.1 Money Currently, academic publishing is dominated by profit-oriented, multinational companies for whom scientific knowledge is a commodity to be sold back to the academic community who created it. The dominant four are Elsevier, Springer Nature, Wiley and Taylor & Francis, which collectively generated over US$7.1 billion in revenue from journal publishing in 2024 alone, and over US$12 billion in profits between 2019 and 2024 (Table 1A). Their profit margins have always been over 30% in the last five years, and for the largest publisher (Elsevier) always over 37%. Against many comparators, across many sectors, scientific publishing is one of the most consistently profitable industries (Table S1). These financial arrangements make a substantial difference to science budgets. In 2024, 46% of Elsevier revenues and 53% of Taylor & Francis revenues were generated in North America, meaning that North American researchers were charged over US$2.27 billion by just two for-profit publishers. The Canadian research councils and the US National Science Foundation were allocated US$9.3 billion in that year. The costs of inaction are plain: wasted public funds, lost researcher time, compromised scientific integrity and eroded public trust. Today, the system rewards commercial publishers first, and science second. Without bold action from the funders we risk continuing to pour resources into a system that prioritizes profit over the advancement of scientific knowledge.
November 11, 2025 at 11:52 AM
Reposted by Neel Shah
biorxivpreprint.bsky.social
Bronsted-basic small molecules activate GTP hydrolysis in Ras Q61 mutants https://www.biorxiv.org/content/10.1101/2025.11.04.686643v1
November 6, 2025 at 6:48 PM
nshahlab.bsky.social
Congrats, Jeanine! @amacherlab.bsky.social
dreyfusfoundation.bsky.social The Camille and Henry Dreyfus Foundation @dreyfusfoundation.bsky.social · 19d
Congratulations to Dr. Jeanine Amacher at Western Washington University for being named a 2025 Henry Dreyfus Teacher-Scholar! #DreyfusAwards
November 6, 2025 at 5:08 PM
Reposted by Neel Shah
stephanhacker2.bsky.social
How can we study target engagement and selectivity of covalent inhibitors? Which electrophilic probes are best suited to study a certain amino acid?

Our study on "Profiling the proteome-wide selectivity of diverse electrophiles" is published in Nature Chemistry.(1/7)

www.nature.com/articles/s41...
Profiling the proteome-wide selectivity of diverse electrophiles - Nature Chemistry
Covalent inhibitors are powerful entities in drug discovery. Now the amino acid selectivity and reactivity of a diverse electrophile library have been assessed proteome-wide using an unbiased workflow...
www.nature.com
October 30, 2025 at 10:27 AM
nshahlab.bsky.social
Congrats, Eunhee and the whole team. This is really cool!
eunheechoilab.bsky.social Eunhee Choi @eunheechoilab.bsky.social · 27d
Excited to share our new publication in Nature Communications! 🧬
We explored how evolution shaped the structure–function relationship of the insulin receptor (IR) family using a simplified model — the fruit fly. 🪰
rdcu.be/eM7zG
October 30, 2025 at 1:00 AM
Reposted by Neel Shah
immunologypodcast.com
New work from the lab of Dr. Wan-Lin Lo at @utah.edu demonstrates that age-dependent Zap70 expression regulates negative selection and thymic #Treg cell development.

Study🗒️: https://go.nature.com/4o9oqWn
Episode 🔊: https://bit.ly/3LlRCeo
October 24, 2025 at 4:52 PM
Reposted by Neel Shah
elhamazizi.bsky.social
Please share🔉 We’re #hiring #AI #Engineers
@columbiaseas.bsky.social @cancerdynamics.bsky.social
🚀Join us to build foundation models that learn & reason about cancer systems, integrating #LLMs #causalAI and multi-modal #genomics. Shape the next-generation of cancer therapies! tinyurl.com/5n7wp8ck
October 24, 2025 at 2:37 PM
Reposted by Neel Shah
chrisgparker.bsky.social
Happy to share the final version of this work out in ACS CS. Inspired by ‘binding-focused’ chemoproteomic methods, we developed a ‘function-focused’ strategy to agnostically identify degradable proteins.
This was a big team effort led by
@inesforrest.bsky.social
and in collaboration with AbbVie.
Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules
Targeted protein degradation (TPD) is an emergent therapeutic strategy with the potential to circumvent challenges associated with targets unamenable to conventional pharmacological inhibition. Among ...
pubs.acs.org
October 21, 2025 at 3:55 PM
Reposted by Neel Shah
lindorfflarsen.bsky.social
We (@sobuelow.bsky.social) developed AF-CALVADOS to integrate AlphaFold and CALVADOS to simulate flexible multidomain proteins at scale

See preprint for:
— Ensembles of >12000 full-length human proteins
— Analysis of IDRs in >1500 TFs

📜 doi.org/10.1101/2025...
💾 github.com/KULL-Centre/...
Figure showing the AF-CALVADOS restraining and simulation protocol based on AF2 structure, PAE and pLDDT
October 20, 2025 at 11:26 AM
Reposted by Neel Shah
cmholab.bsky.social
Learn how our hunt for the native structure of top antimalarial target PfATP4🧂led to the discovery of PfABP, an unknown essential binding partner, out now! @natcomms.nature.com 👉 rdcu.be/eLRlH 🦠🔬❄️

A team effort led by @mehsehret.bsky.social & Anurag Shukla @akhilvaidya.bsky.social! #cryoEM #malaria
Endogenous structure of antimalarial target PfATP4 reveals an apicomplexan-specific P-type ATPase modulator
Nature Communications - Here, the authors present the 3.7 Å cryoEM structure of native sodium efflux pump PfATP4 from Plasmodium falciparum, revealing a bound protein that they term...
rdcu.be
October 20, 2025 at 12:55 PM
nshahlab.bsky.social
Happy to share that our paper with Harmen Bussemaker’s group entitled “Accurate affinity models for SH2 domains from peptide binding assays and free-energy regression” is out in its final form at Protein Science!

onlinelibrary.wiley.com/doi/10.1002/...
October 16, 2025 at 12:40 AM
Reposted by Neel Shah
glukozica.bsky.social
Skeetorial on our BRAF preprint!
tinyurl.com/asymmBRAF
The RAS->RAF->MEK->ERK cascade carries mutations in most human cancers. Interestingly, although we have three RAF paralogues (A, B and C), it is the BRAF that is predominantly mutated in cancer patients. (1/10)
Mechanism of MEK1 phosphorylation by the N-terminal acidic motif-mediated asymmetric BRAF dimer
The RAF/MEK/ERK signaling cascade regulates cell proliferation and differentiation and is frequently dysregulated in cancer. Approximately 90% of RAF-mutant cancers harbour mutations in B-type of Rapi...
tinyurl.com
October 14, 2025 at 8:17 AM
Reposted by Neel Shah
eunayoo.bsky.social
Our work on developing a fluorescent probe to measure granzyme B activity in anti-tumor immunity is finally out! pubs.acs.org/doi/10.1021/...
Granzyme B-Targeting Quenched Activity-Based Probes for Assessing Tumor Response to Immunotherapy
Molecular imaging of immune activation holds tremendous potential for the development of novel immunotherapies. In particular, chemical probes capable of detecting immune responses before changes in t...
pubs.acs.org
October 8, 2025 at 11:44 PM
Reposted by Neel Shah
chemkritzer.bsky.social
Come be my colleague! Tufts Chemistry is hiring a tenure-track Assistant Professor working on materials with energy applications. We have a fantastic, supportive environment for you to start your research career. Send questions to me or @chemysl.bsky.social

apply.interfolio.com/175284
October 6, 2025 at 12:02 PM
Reposted by Neel Shah
pracheeac.bsky.social
New Blog Post:
Scholarly Communication Is a Research Problem. This Means You.

pracheeac.substack.com/p/scholarly-...
Scholarly Communication Is a Research Problem. This Means You.
Scholarly Communication Is a Research Problem.
pracheeac.substack.com
October 4, 2025 at 4:11 PM
Reposted by Neel Shah
jasonzxzhang.bsky.social
Excited to share our latest work in expanding AI-based protein design into targeting PTMs! I’m particularly excited in this work as there is so much we don’t know about PTMs despite their central role in signaling and hopefully we can start to decode their rules and functions.
kinasekid.bsky.social Magnus Bauer @kinasekid.bsky.social · Sep 30
Phosphorylation on tyrosines control key pathways in immunity, cancer, and metabolism. For the first time, we can now design proteins that specifically recognize individual phosphotyrosines, even in disordered regions. (1/8)

Preprint: www.biorxiv.org/content/10.1...
September 30, 2025 at 11:42 PM
Reposted by Neel Shah
kinasekid.bsky.social
Phosphorylation on tyrosines control key pathways in immunity, cancer, and metabolism. For the first time, we can now design proteins that specifically recognize individual phosphotyrosines, even in disordered regions. (1/8)

Preprint: www.biorxiv.org/content/10.1...
September 30, 2025 at 9:55 PM
Reposted by Neel Shah
jlmcfalinefigueroa.bsky.social
We’re hiring!📣

Exciting opportunity at the Irving Institute for Cancer Dynamics and School of Engineering and Applied Science at Columbia: Associate Research Scientist. Lead pooled CRISPR + Perturb-seq screens to close AI-identified knowledge gaps. Apply apply.interfolio.com/172825
Apply - Interfolio {{$ctrl.$state.data.pageTitle}} - Apply - Interfolio
apply.interfolio.com
September 29, 2025 at 10:32 PM
Reposted by Neel Shah
glukozica.bsky.social
First work on kinases from my lab! Working on this project, I often remembered the late Cyrus Chothia who said that if the data doesn’t fit a beautiful model, maybe it’s not the model, maybe you just need more data. :)
biorxiv-biochem.bsky.social bioRxiv Biochemistry @biorxiv-biochem.bsky.social · Sep 27
Mechanism of MEK1 phosphorylation by the N-terminal acidic motif mediated asymmetric BRAF dimer https://www.biorxiv.org/content/10.1101/2025.09.26.678760v1
September 28, 2025 at 10:33 AM
Reposted by Neel Shah
sonjalorenzlab.bsky.social
Allosteric activation of a ubiquitin ligase by an internal kinase domain! Congratulations to our team member Thornton Fokkens for this fascinating discovery in a neglected disease area with strong therapeutic need. Many thanks to all our great collaborators!
www.sciencedirect.com/science/arti...
A Leishmania virulence factor harnesses an allosteric kinase switch to regulate its ubiquitin ligase activity
Stringent control of ubiquitylation is a central requirement of signaling specificity in eukaryotes. Here, we discover a domain module integrating pro…
www.sciencedirect.com
September 24, 2025 at 3:30 PM