Unique structural and ligand-binding properties of the Staphylococcus aureus serine hydrolase FphE | PNAS Staphylococcus aureus is a human pathogen capable of forming biofilms that complicate treatment and facilitate chronic infections. A family of S. a...

Our latest work on the somewhat enigmatic serine hydrolase FphE from S. aureus is out. This work provides interesting structural and ligand binding insights that help to explain its biological functions. With @mfellnerlab.bsky.social - University of Otago.

www.pnas.org/doi/10.1073/pnas.2532683123

Our latest work on fluorescent probes for imaging infections in vivo is out. Check it out!

www.biorxiv.org/content/10.6...

Looking forward to the biannual #CBP2025 conference @ohsunews.bsky.social starting this week! incredible line up of speakers, including keynotes @mbogyo.bsky.social, @christhechang.bsky.social, and Nancy Carrasco.

www.ohsu.edu/school-of-me...

A pipeline for proteome-wide analysis of electrophile selectivity - Nature Chemistry In the growing field of chemical proteomics, there is a need for general methods to map the reactivity profiles of covalent probes in complex proteomes. Now, a completely unbiased proteomic workflow h...

Our new Nature Chemistry paper is also accompanied by an insightful News and Views article by @jeyunjo.bsky.social and @mbogyo.bsky.social.
Check it out here: www.nature.com/articles/s41...
Thank you very much for the kind comments on our work!

Our latest work developing AND-gate probes to image inflammation is out. Great work from Shiyu Chen and collaboration with the group at Merck.

pubs.acs.org/articlesonre...

A Bacteroides fragilis protease activates host PAR2 to induce intestinal pain and inflammation Lakemeyer and colleagues analyze the secretome of gut bacteria to identify factors that target host PAR2. They find that the Bacteroides fragilis protease Bfp1 cleaves and activates PAR2, disrupting i...

After a long journey and much hard work from many talented scientists, our paper is finally out. Take a look if you are interested in proteases and host microbe interactions in the gut. www.cell.com/cell-host-mi...

Home | MIRC Advancements in Osteoarthritis: From Discovery to Treatment

Thrilled to be speaking at the McCaig International Research Conference on #Osteoarthritis, March 11–13, 2026 in Kananaskis, Alberta 🇨🇦.
Trainee abstract submissions open until Oct 31, 2025!

mccaig.ucalgary.ca/event/intern...

#McCaig2026 #BoneAndJointHealth

A Two-Step Synthesis of Covalent Genetically-Encoded Libraries of Peptide-Derived Macrocycles (cGELs) enables use of electrophiles with diverse reactivity Genetically-encoded libraries of peptide-derived macrocycles containing electrophile "warheads" (cGELs) can be used to identify potent and selective covalent ligands for protein targets. Such cGELs ar...

Great collaboration with @derda_lab @RatmirDerda just posted to bioRxiv. Check out how to best incorporate electrophiles into cyclic peptides to generate covalent inhibitors. www.biorxiv.org/content/10.1...

Having a great time as a senior visiting faculty at Nanyang Technological University in Singapore hosted by Professor Kanyi Pu. Great people and great science.

Macrocyclic Phage Display for Identification of Selective Protease Substrates Traditional methods for identifying selective protease substrates have primarily relied on synthetic libraries of linear peptides, which offer limited sequence and structural diversity. Here, we present an approach that leverages phage display technology to screen large libraries of chemically modified cyclic peptides, enabling the identification of highly selective substrates for a protease of interest. Our method uses a reactive chemical linker to cyclize peptides on the phage surface, while simultaneously incorporating an affinity tag and a fluorescent reporter. The affinity tag enables capture of the phage library and subsequent release of phages expressing optimal substrates upon incubation with a protease of interest. The addition of a turn-on fluorescent reporter allows direct quantification of cleavage efficiency throughout each selection round. The resulting identified substrates can then be chemically synthesized, optimized and validated using recombinant enzymes and cells. We demonstrate the utility of this approach using Fibroblast Activation Protein α (FAPα) and the related proline-specific protease, dipeptidyl peptidase-4 (DPP4), as targets. Phage selection and subsequent optimization identified substrates with selectivity for each target that have the potential to serve as valuable tools for applications in basic biology and fluorescence image-guided surgery (FIGS). Overall, our strategy provides a rapid and unbiased platform for effectively discovering highly selective, non-natural protease substrates, overcoming key limitations of existing methods.

Macrocyclic Phage Display for Identification of Selective Protease Substrates | Journal of the American Chemical Society pubs.acs.org/doi/full/10....

Our paper outlining a new method for identifying selective protease substrates by phage display is finally out. Nice work from @mbarniolx.bsky.social. pubs.acs.org/doi/full/10....

A caspase-1-cathepsin AND-gate probe for selective imaging of inflammasome activation Caspase-1 is a key mediator of the inflammasome pathway, which is associated with several inflammatory disorders including obesity, diabetes mellitus (DM), cardiovascular diseases (CVDs), cancers and ...

Our latest work developing AND-gate probes for imaging caspase-1 mediated inflammation is out. Very productive collaboration with Merck & Co. in South San Francisco. #chembio. www.biorxiv.org/content/10.1...

This work shows that it is possible to find highly potent and selective covalent inhibitors of an enzyme target directly from small fragment libraries containing diverse electrophiles. These new tools can be used to study the function of these bacterial hydrolases which are important for virulence.

Identification of covalent inhibitors of Staphylococcus aureus serine hydrolases important for virulence and biofilm formation - Nature Communications Staphylococcus aureus is a leading cause of bacteria-associated mortality worldwide. New tools are needed to both image and treat this pathogen. We previously identified a group of S. aureus serine hy...

Our work identifying new covalent inhibitors of Staphylococcus aureus serine hydrolyses from fragment libraries is out! great work from @tulsiupadhyay.bsky.social and our many collaborators, including @christianslentz.bsky.social, @mfellnerlab.bsky.social. #chembio
link.springer.com/article/10.1...

The phase IIb results from the multi center trail of our cathepsin probe (VGT-309/abenacianine) are out. The probe met its endpoints and resulted in significant clinical events in 45% of patients. Great work by Vergent Biosciences and Dr. Sunil Singhal (UPenn).

www.vergentbio.com/press-releas...

Fishing for covalent peptides Nature Chemical Biology - Electrophilic phage display has emerged as a powerful platform for discovering high-affinity or covalent peptide ligands. A new study reveals that this platform enables...

Check out the nice News and Views article about our work from lead author @sijiewang.bsky.social using phage display to find covalent inhibitors of protein-protein interactions. #ChemBio
www.nature.com/articles/s41...

Flyer for the 2025 Next Generation Faculty Symposium (including QR code in top right corner). This symposium highlights the work of exceptional early-career scientists in the broad field of quantitative biological and biomedical sciences, with a track record of excellence in research, leadership, mentorship, and community engagement. These early career scientists are preparing to launch a faculty search. Applications are due May 30th, 2025.

Hello Community!
Are you a postdoc/grad student preparing to launch a faculty search? Do you have a track record of excellence in research, leadership, mentorship & community engagement? Apply to the 2025 Next Generation Faculty Symposium: www.berkeleystanfordnextgensymposium.com! Pls repost! (1/3)

Chemical strategies for targeting lipid pathways in bacterial pathogens Microbial pathogens continue to plague human health and develop resistance to our current frontline treatments. Over the last few decades, there has b…

If you are interested in lipids in bacteria, check out this awesome new review written by my talented student Alyssa Carter, super postdoc Emily Woods and me. #chembio
www.sciencedirect.com/science/arti...

Great visit to Melbourne Uni to give a talk and visit with my former PhD student Laura Edgington-Mitchell and her lab.

Had a great time at #ABPP2025! Great to see so many former lab members and their students and postdocs. Awesome venue and program. Looking forward to ABPP2027 in Leiden and then Ben Cravatt and I will try to bring it to California!

Visualization of calpain-1 activation during cell death and its role in GSDMD cleavage using chemical probes Horbach et al. developed chemical tools to study calpain-1 activation during pyroptosis. Using mass cytometry and IQF substrates, the authors show that calpain-1 correlates with GSDMD and caspase-1 in immune cells. They also demonstrate that calpain-1 cleaves GSDMD at a putative QRTF/Q, potentially supporting pyroptosis process.

Online now! #chembiol

Engineered commensals for targeted nose-to-brain drug delivery Shen et al. investigate the use of Lactobacillus plantarum, a commensal bacterial strain, as a chassis for targeting the olfactory mucosa to facilitate precise nose-to-brain delivery of therapeutic mo...

Engineered commensals for targeted nose-to-brain drug delivery www.cell.com/cell/fulltex...

Great keynote of @mbogyo.bsky.social to kick off the second day of #ABPP2025 Impressive progress on probes for image guided surgery and for detection of Staphylococcus aureus.

See you soon!

Great work. Nice to see it out here.

NIH Grants Fueled $95 Billion In FY 2024 Economic Activity, Finds New Report National Institutes of Health grants generated almost $95 billion in economic activity nationwide in FY 2024 according to a new report by United for Medical Research.

NIH is the best investment there is.

www.forbes.com/sites/michae...

Prohormone cleavage prediction uncovers a non-incretin anti-obesity peptide - Nature Computational drug discovery is used to identify a 12-mer peptide derived from BRINP2 with potent anti-obesity effects that are independent of leptin, glucagon-like peptide 1 receptor and melanocortin...

Exciting discovery by Svensson lab and collaborators @stanfordmedicine.bsky.social, computational discovery of 2500 new bioactive peptides, including 12-mer named BRP that reduces food intake leading to weight loss w/o nausea in mice!

www.nature.com/articles/s41...

Comprehensive identification of β-lactam antibiotic polypharmacology in Mycobacterium tuberculosis Infections with Mycobacterium tuberculosis (Mtb) cause tuberculosis (TB), which requires at least six months of treatment with multiple antibiotics. There is emergent interest in using β-lactam antibi...

What are the targets of beta-lactam antibiotics in Mycobacterium tuberculosis? Find out here...
www.biorxiv.org/content/10.1...

Dr. Collins noted that when he was recruited to the institutes, and through many of the years that followed, “investment in medical research was seen as a high priority and a nonpolitical bipartisan effort — saving countless lives, relieving human suffering and contributing substantially to the U.S. economy.” “N.I.H. is the largest supporter of biomedical research in the world,” he wrote. “It is the main piston of a biomedical discovery engine that is the envy of the globe. Yet it is not a household name. It should be.” He went on: “When you hear about patients surviving stage 4 cancer because of immunotherapy, that was based on N.I.H. research over many decades. When you hear about sickle-cell disease being cured because of CRISPR gene editing, that was built on many years of research supported by N.I.H.”

Francis Collins led the mapping of the human genome, and chose to do big scientific to benefit the public. He is a a former NIH Director.
He just resigned his position in government. His resignation letter:
www.nytimes.com/2025/03/01/u...

#chembio