Neel Shah

The Gonzalez Lab at Columbia University is seeking a scientific leader!

Join us in a Research Scientist position, driving single-molecule, structural, and biochemical studies of translation, translational control, and other RNA-based processes.

Apply: apply.interfolio.com/176949

Janelia is hiring! "Invent new imaging methods, molecular tools, or protein chemistry approaches"

www.janelia.org/content/lead...

2025 ISB Virtual Microbiome Symposium - Institute for Systems Biology (ISB) The gut’s microbial ecosystem produces diverse metabolites that actively shape neural, immune, and endocrine function. Join leading researchers on December 12 as they share new discoveries into these ...

Please join us on Dec 12th for the 2025 @isbscience.org Virtual Microbiome Symposium, focused on "Gut Microbial Metabolites and Their Impact on Host Systems".

Co-organized by @gibbological.bsky.social

Registration is free & we have a fantastic line-up of experts!

isbscience.org/events/2025-...

@isbscience.org's Dr. Mary Brunkow gave a "practice talk" for her Nobel Lecture, and it was riveting! Mapping the Foxp3 locus was an arduous task in the late 90s, and this recognition is a fitting tribute. Thrilled for you, Mary! Your humility and grace are a wonderful example for all of us.

Enhanced S-Palmitoylated Protein Detection by Mild Nonionic Detergent in Proteomic Workflow Loss of hydrophobic peptides and proteins remains a significant challenge in bottom-up proteomics, resulting in under-representation of membrane and membrane-associated proteins that are critical for ...

You have a problem with identifying hydrophobic proteins in proteomic experiments? So did Hyojung Kim in my lab and the entire protein palmitoylation field. Because -

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Enhanced S-Palmitoylated Protein Detection by Mild Nonionic Detergent in Proteomic Workflow | pubs.acs.org/doi/full/10....

Picture of the bay bridge at night.

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!

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 ...

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...

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FlAsH-ID: A short peptide tag for live cell photoproximity labeling https://www.biorxiv.org/content/10.1101/2025.10.24.684417v1

📢 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

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/...

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.

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:

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Drain: arxiv.org/abs/2511.04820
Strain: direct.mit.edu/qss/article/...
Oligopoly: direct.mit.edu/qss/article/...

Bronsted-basic small molecules activate GTP hydrolysis in Ras Q61 mutants https://www.biorxiv.org/content/10.1101/2025.11.04.686643v1

Congrats, Jeanine! @amacherlab.bsky.social

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...

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...

Congrats, Eunhee and the whole team. This is really cool!

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

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

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 ...

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.

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/...

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...

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

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/...

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...

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)

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...

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/...

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

Scholarly Communication Is a Research Problem. This Means You. Scholarly Communication Is a Research Problem.

New Blog Post:
Scholarly Communication Is a Research Problem. This Means You.

pracheeac.substack.com/p/scholarly-...

Excited to dig into this! Congrats to the whole team!

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.

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...

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

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. :)