Sam Barnett Dubensky

Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits Gene regulatory networks encode the fundamental logic of cellular functions, but systematic network mapping remains challenging, especially in cell states relevant to human biology and disease. Here, ...

Together with @ronghuizhu.bsky.social, we are thrilled to present our new perturb-seq study of 22M primary CD4+ T cells, across donors and timepoints – the result of a decade-long collaboration between the Marson @marsonlab.bsky.social and Pritchard @jkpritch.bsky.social labs 🧵 tinyurl.com/gwt2025

Multimodal analysis defines GNG4 as a distinguishing feature of germinal center-positioned CD4 T follicular helper cells in humans @biorxivpreprint.bsky.social
www.biorxiv.org/content/10.6... @lauravella.bsky.social @derek-oldridge.bsky.social @pennmedicine.bsky.social

Really excited to share this work from the @laura-a-vella.bsky.social and @derek-oldridge.bsky.social labs, led by an amazing MD/PhD student! Sam asked if Tfh spatially localised within germinal centers have distinct gene expression programs & identified GNG4 as a key feature of GC-positioned Tfh.

Distinct components of mRNA vaccines cooperate to instruct efficient germinal center responses This study dissects the individual contributions of the different components of mRNA vaccines to immune responses. Nucleoside-modified mRNA promotes the production of type I interferons that act on de...

I am excited to share that our work, in which we have dissected the signals driven by the nucleoside-modified mRNA and LNP components of mRNA vaccines that regulate germinal center (GC) responses, is now published in Cell! www.cell.com/cell/fulltex...

@biorxivpreprint.bsky.social Dysregulated localization of Tfh and B cells in lymph nodes of Idiopathic multicentric Castleman disease patients
www.biorxiv.org/content/10.6... @davidfajgenbaum.bsky.social

Multimodal analysis defines GNG4 as a distinguishing feature of germinal center-positioned CD4 T follicular helper cells in humans CD4 T follicular helper (Tfh) cells coordinate humoral immune responses within germinal centers (GC) of lymphoid tissue. Despite their critical roles in vaccination and autoimmunity, the gene expressi...

T follicular helper cells adopt alter egos and localize to diverse niches - what gene expression programs distinguish Tfh in the germinal center? After dissociating tissue samples into single-cell suspension, can we infer which Tfh were positioned in GCs? Check out our new preprint! bit.ly/3XVsrCI

Very proud to share Sam’s work, jointly supervised between @laura-a-vella.bsky.social and my lab. His work exemplifies how to leverage the power of single-cell and spatialomics to uncover new insights into human GC Tfh biology and why studying human immunology matters:

bsky.app/profile/sbar...

Incredibly happy to share Sam’s work between my lab and that of @derek-oldridge.bsky.social. What cellular programs are engaged by GC-positioned human Tfh? The answers held a few surprises.

Dysregulated lymphocyte localization in idiopathic multicentric Castleman disease https://www.biorxiv.org/content/10.64898/2025.12.12.693846v1

Dysregulated lymphocyte localization in idiopathic multicentric Castleman disease https://www.biorxiv.org/content/10.64898/2025.12.12.693846v1

Beyond commentary on Tfh subsets and GC biology, expect plenty of bread and baking-related content from this Bluesky page going forward - my sourdough starter is even older than my current year of MD/PhD training!

Lastly, please reach out if you have any ideas or questions regarding our preprint!

Multimodal analysis defines GNG4 as a distinguishing feature of germinal center-positioned CD4 T follicular helper cells in humans CD4 T follicular helper (Tfh) cells coordinate humoral immune responses within germinal centers (GC) of lymphoid tissue. Despite their critical roles in vaccination and autoimmunity, the gene expressi...

And don't forget about the supplementary section! bit.ly/48HftyM

Beyond supporting data and figures, there we describe our bioinformatic methods in depth to aid open communication and reproducibility. Code and data will also soon be on GitHub and Zenodo for reanlaysis:
bit.ly/4q8nkuX
bit.ly/3L3v6r5

Further, we received key samples and insights from the Romberg and Henrickson Labs at CHOP. I also want to thank my thesis committee for their guidance: Sarah Henrickson, Taku Kambayashi, David Hill, and Chris Hunter.

@romberglab.bsky.social
@sarahhenrickson.bsky.social
@kingofpathogens.bsky.social

I have been lucky to work alongside my coauthors in both the Oldridge and Vella Labs, including Amy Baxter who is now leading a new group at I3H!

@derek-oldridge.bsky.social
@laura-a-vella.bsky.social
@amylizbaxter.bsky.social
@pennmedcso.bsky.social
@chopresearch.bsky.social
@i3h-upenn.bsky.social

A fresh look at the T helper subset dogma - PubMed Single-cell sequencing techniques enable the decades-old T helper subset dogma to be approached in an unsupervised manner, bringing nuances to the definition of known subsets, while simultaneously identifying interesting novel cell states.

Further, we use our high-plex data to ask how several clinically important axes of Tfh variation are integrated within single Tfh states, such as polarity (e.g. Tfh1 vs Tfh2 vs Tfh17) and Tem vs Tcm-like phenotypes. If you want to try every scoop in the parlor, these data are for you bit.ly/3MvcjFH

Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis - PubMed Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide associ …

Through reanalysis of published vaccination scRNAseq, rheumatoid arthritis GWAS, and T cell eQTL data, we propose roles for elevated GNG4 expression in human immune health and disease. Here I would like to thank @saorisakaue.bsky.social and colleagues for discussing their study! bit.ly/4pX9bBj

Even more surprising was when Melanie Mumau and the Fajgenbaum Lab approached us with new data from lymph nodes of patients with Castleman disease - in this context, both Tfh positioning and GNG4 expression were highly dysregulated. Check out their preprint for more!

@davidfajgenbaum.bsky.social

Using spatially resolved and multimodal single-cell analyses of human tonsil and blood, we unexpectedly converged upon GNG4 as a distinguishing feature of GC-localized Tfh. GNG4 encodes G protein subunit gamma 4, a modulator of GPCR signaling most known for its roles in neurons and cancer biology.

Multimodal analysis defines GNG4 as a distinguishing feature of germinal center-positioned CD4 T follicular helper cells in humans CD4 T follicular helper (Tfh) cells coordinate humoral immune responses within germinal centers (GC) of lymphoid tissue. Despite their critical roles in vaccination and autoimmunity, the gene expressi...

T follicular helper cells adopt alter egos and localize to diverse niches - what gene expression programs distinguish Tfh in the germinal center? After dissociating tissue samples into single-cell suspension, can we infer which Tfh were positioned in GCs? Check out our new preprint! bit.ly/3XVsrCI

Multimodal analysis defines GNG4 as a distinguishing feature of germinal center-positioned CD4 T follicular helper cells in humans https://www.biorxiv.org/content/10.64898/2025.12.10.693235v1

Multimodal analysis defines GNG4 as a distinguishing feature of germinal center-positioned CD4 T follicular helper cells in humans https://www.biorxiv.org/content/10.64898/2025.12.10.693235v1