Thomas Kislinger

Pan-cancer N-glycoproteomic atlas of patient-derived xenografts uncovers FAT2 as an actionable surface target Govindarajan et al. leverage N-glycoproteomics and PDX models to decode the in vivo cancer cell surfaceome and establish Glyco PDXplorer—a target discovery platform. The identification and validation of FAT2 as a previously undescribed, actionable antigen demonstrates the utility of Glyco PDXplorer for uncovering therapeutic vulnerabilities.

Online now: Pan-cancer N-glycoproteomic atlas of patient-derived xenografts uncovers FAT2 as an actionable surface target

Raising a novel antibody, we demonstrate that FAT2 expression is associated with patient outcome. Reformatting to a CAR-T demonstrated anti-tumor activity in pre-clinical models.

We develop a PDX-based N-glycoproteomics strategy to discover cancer-enriched cell surface targets and identify FAT2 as a novel, largely unexplored squamous cell marker that is essential for cellular growth and survival.

Checkout our new paper published in @cp-cellrepmed.bsky.social

www.cell.com/cell-reports...

Fantastic work by Meinusha Govindarajan and Salvador Mejia-Guerrero with lots of help from our many collaborators and colleagues. #glycotime

Interested in surface proteomics for drug discovery?? Come to our @hupo-org.bsky.social Workshop on Sunday, Nov 9 at HUPO in Toronto! Excited to host with Amanda Lorentzain and learn from @berndwollscheid.bsky.social, Susan Klaeger and Thomas Kislinger!

CNPN2025 will be held on November 8th to kick off HUPO2025!

We have the honor to introduce our keynote speaker and fantastic invited speaker 🥳
@kislingerthomas.bsky.social and @philipplange.bsky.social

For more info about the program: cnpn.ca/cnpn2025/

#precisionmedicine #biomarkerdiscovery

Pan-cancer N-glycoproteomic atlas of patient-derived xenografts uncovers FAT2 as a therapeutic target for head and neck cancers Cell surface proteins offer significant cancer therapeutic potential attributable to their accessible membrane localization and central role in cellular signaling. Despite this, their promise remains ...

And in case you missed it, here is her second, equally impressive second preprint.
www.biorxiv.org/content/10.1...

Surface proteomics reveals arginine metabolism as a vulnerability in high grade serous ovarian cancer The significant lethality of high-grade serous ovarian cancer (HGSC) is driven by the lack of long- term efficacy of current treatments, underscoring the need for developing additional therapeutics. C...

Latest preprint from the lab. Great work as always by Meinusha. This is the last chapter for her PhD.
www.biorxiv.org/content/10.1...

Ancestry-Dependent Immunologic and Prognostic Effects Characterize the Prostate Cancer Urinary Proteome - PubMed Urine is an attractive biomarker analyte for non-invasive longitudinal monitoring of health and disease, particularly for diseases of the genitourinary tract, like prostate and bladder cancer. The com...

pubmed.ncbi.nlm.nih.gov/40894632/

Interestingly, the urinary proteome of Black patients harboured more features of aggressive cancers than those of grade- and PSA-matched White patients. These observations highlight the importance of controlling for ancestry-associated differences in biomarker development.

This cohort was stratified by ancestry – thought to be a risk-factor for aggressive disease. We found surprisingly large differences and dysregulation of immune pathways.

After nearly 15 years of urine proteomics of prostate cancer patients, this is our most comprehensive work to date. We generated spectral libraries from hundreds of samples to rapidly analyze 329 post-DRE urines.

Ancestry-Dependent Immunologic and Prognostic Effects Characterize the Prostate Cancer Urinary Proteome Urine is an attractive biomarker analyte for non-invasive longitudinal monitoring of health and disease, particularly for diseases of the genitourinary tract, like prostate and bladder cancer. The com...

Checkout our latest pre-print
www.biorxiv.org/content/10.1...

Phenotypic screens for SIRPA expression reveal RAB21 as a general regulator of macrophage surface identity Through CRISPR screening, Granda Farias et al. find results consistent with cis CD47-SIRPA interactions relying on QPCTL and that RAB21/Rab21 inactivation reduces macrophage model surface SIRPA/Sirpa ...

Phenotypic screens for SIRPA expression reveal RAB21 as a general regulator of macrophage surface identity: Cell Reports www.cell.com/cell-reports...

Identification of non-canonical peptides with moPepGen - Nature Biotechnology moPepGen enables the detection of peptides across species, proteases and technologies.

‪checkout our latest paper in @natbiotech.nature.com . We developed a graph-based algorithm that comprehensively generates non-canonical peptides in linear time. www.nature.com/articles/s41...

Identification of non-canonical peptides with moPepGen - Nature Biotechnology moPepGen enables the detection of peptides across species, proteases and technologies.

Identification of non-canonical peptides with moPepGen - @uclahealth.org @uoftmedicine.bsky.social @kislingerthomas.bsky.social go.nature.com/3HYJyyz

Cerebrospinal fluid protein biomarkers are associated with response to multiagent intraventricular chemotherapy in patients with CNS lymphoma - PubMed The study identified CSF-based proteomic biomarkers, particularly LCP1, that can classify MAIVC response and indicate tumor burden in CNSL patients.

New collaborative work from PhD student Aastha. Using proteomics for CSF-based biomarker discovery

pubmed.ncbi.nlm.nih.gov/40321620/

CSF protein biomarkers are associated with response to multi-agent intraventricular chemotherapy in patients with CNS lymphoma AbstractBackground. Central nervous system lymphoma (CNSL), is a rare subtype of non-Hodgkin lymphoma, primarily affecting the brain and spinal cord. Most

academic.oup.com/noa/advance-...

Recent implementations of data-independent acquisition for cancer biomarker discovery in biological fluids - PubMed Various studies showed the potential of DIA-MS in identifying putative cancer biomarkers in a high-throughput manner. However, the lack of proper study design and standardization of methods across pla...

New review from our team.

pubmed.ncbi.nlm.nih.gov/40227112/

I am everywhere and nowhere 👻

Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes - Nature Communications ‘Engraftment of patient-derived xenografts in samples from head and neck squamous cell carcinoma is variable. Here, the authors use transcriptomic and proteomic profiling to correlate engraftment of P...

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

Last paper for 2024. Nice work by PDF Matt Waas on proteomics of HNSCC tissues to identify novel biomarkers within the N0 population. Great collaboration with Laurie Ailles
and support from many colleagues Princess Margaret Cancer Centre

Definitely also expressed in skin.

It gets upregulated in squamous carcinomas and is required for growth and survival

There is expression in the cerebellum for sure.
Might be through that route
Not sure how it gets into milk. Maybe low level expression in some mammary epithelial populations. I will look at our own CSF, urine and normal mammary populations tomorrow.

Actually most datasets correlate reasonable well for Fat2. Since I have worked on this protein for the last 8 years

Let us know your thoughts

Pan-cancer N-glycoproteomic atlas of patient derived xenografts uncovers FAT2 as a therapeutic target for head and neck cancers https://www.biorxiv.org/content/10.1101/2024.12.11.627962v1

Pan-cancer N-glycoproteomic atlas of patient derived xenografts uncovers FAT2 as a therapeutic target for head and neck cancers https://www.biorxiv.org/content/10.1101/2024.12.11.627962v1