Struan Grant

Congratulations to my labmates @junzhong.bsky.social and Aidan for their new publication on non-coding somatic mutations in PDAC! I’m honored to have been a part of the work & @amundadottir.bsky.social team.

Large-scale multiomic analysis identifies non-coding somatic driver mutations and nominates ZFP36L2 as a driver gene for pancreatic ductal adenocarcinoma Background The identification and characterisation of somatic cancer driver mutations in the non-coding genome remains challenging. Objective To broadly characterise non-coding driver mutations for p...

So excited that our manuscript is now online! Led by the super talented @junzhong.bsky.social & Aidan O'Brien in my lab with lots of help from Minal Patel @kconnelly92.bsky.social Jason Hoskins @efsunarda.bsky.social @struangrant.bsky.social and others. Very grateful to our team and collaborators!!

Always one of the best moments in research and very pound to be in the @amundadottir.bsky.social team!

Large-scale multiomic analysis identifies non-coding somatic driver mutations and nominates ZFP36L2 as a driver gene for pancreatic ductal adenocarcinoma Background The identification and characterisation of somatic cancer driver mutations in the non-coding genome remains challenging. Objective To broadly characterise non-coding driver mutations for p...

Congratulations to the @amundadottir.bsky.social team for their #Gut paper reporting a large-scale multiomic analysis of pancreatic ductal adenocarcinoma. Delighted to contribute along with @adwellspenn.bsky.social. @chopresearch.bsky.social @penngenetics.bsky.social

gut.bmj.com/content/earl...

@upenngcb.bsky.social

Great work from the co-leaders of the study: Mitch Conery, Jim Pippin, Yadav Wagley, @khanhtrang.bsky.social, @bvoight28.bsky.social, Kurt Hankenson and @alessandrachesi.bsky.social

GWAS-informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density - Genome Biology Background Over 1100 independent signals have been identified with genome-wide association studies (GWAS) for bone mineral density (BMD), a key risk factor for mortality-increasing fragility fractures; however, the effector gene(s) for most remain unknown. Results We execute a CRISPRi screen in human fetal osteoblasts (hFOBs) with single-cell RNA-seq read-out for 89 non-coding elements predicted to regulate osteoblast gene expression at BMD GWAS loci. The BMD relevance of hFOBs is supported by heritability enrichment from stratified LD-score regression involving 98 cell types grouped into 15 tissues. Twenty-three genes show perturbation in the screen, with four (ARID5B, CC2D1B, EIF4G2, and NCOA3) exhibiting consistent effects upon siRNA knockdown on three measures of osteoblast maturation and mineralization. Lastly, additional heritability enrichments, genetic correlations, and multi-trait fine-mapping unexpectedly reveal that many BMD GWAS signals are pleiotropic and likely mediate their effects via non-bone tissues. Conclusions Our results provide a roadmap for how single-cell CRISPRi screens may be applied to the challenging task of resolving effector gene identities at all BMD GWAS loci. Extending our CRISPRi screening approach to other tissues could play a key role in fully elucidating the etiology of BMD.

Our latest paper, just out in #GenomeBiology: "GWAS-informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density". @chopresearch.bsky.social @penngenetics.bsky.social
genomebiology.biomedcentral.com/articles/10....

Re-posting given recent adds
go.bsky.app/9asWtuD

Post Doctoral Research Fellow – Circadian Biology and Genomics in Philadelphia, Pennsylvania, United States of America | Fellows, Students & Interns at Children’s Hospital of Philadelphia Apply for Post Doctoral Research Fellow – Circadian Biology and Genomics job with Children’s Hospital of Philadelphia in Philadelphia, Pennsylvania, United States of America. Fellows, Students & Inter...

My lab is seeking to co-hire a postdoctoral fellow with the
@shaonsengupta.bsky.social team. See details below!

I'll be #ASHG2025, so open to discuss further there if interest.

careers.chop.edu/us/en/job/10...

To say that "the data show these vaccines fail" in regards to the mRNA plaform is unforgivable.

For those of you that don't remember - this is the data from a SINGLE dose. In December 2020. So good I cried in grateful tears.

Post Doctoral Research Fellow – Circadian Biology and Genomics in Philadelphia, Pennsylvania, United States of America | Fellows, Students & Interns at Children’s Hospital of Philadelphia Apply for Post Doctoral Research Fellow – Circadian Biology and Genomics job with Children’s Hospital of Philadelphia in Philadelphia, Pennsylvania, United States of America. Fellows, Students & Inter...

My lab is seeking to co-hire a postdoctoral fellow with the @shaonsengupta.bsky.social team. See details below!

careers.chop.edu/us/en/job/10...

Obesity Prediction Could Be Guided by Genetic Risk Scores

Delighted to contribute, along locally with @alessandrachesi.bsky.social and @jonathanbradfield.bsky.social‬: "Polygenic prediction of body mass index and obesity through the life course and across ancestries".

www.nytimes.com/2025/07/21/h...

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

Lineage-resolved analysis of embryonic gene expression evolution in C. elegans and C. briggsae The constraints that govern the evolution of gene expression patterns across development remain unclear. Single-cell RNA sequencing can detail these constraints by systematically profiling homologous ...

Happy to announce our paper comparing embryonic gene expression between C. elegans and C. briggsae, work led by Christopher Large with Rupa Khanal and in collaboration with Junhyong Kim and Bob Waterston. www.science.org/doi/10.1126/...

Excited to to see our collaboration with @gburslem.bsky.social published today! This is part of our ongoing long term goal of achieving scalable non-disruptive and direct imaging and perturbation of the endogenous proteome

Inside AJHG: A Chat with Max Dudek Editors of The American Journal of Human Genetics sat down with Max Dudek, BS, to discuss his recently published paper, “Characterization of non-coding variants associated with transcription-factor bi...

Great to see @maxdudek.bsky.social in the @upenngcb.bsky.social program interviewed by @ajhgnews.bsky.social

www.ashg.org/ajhg/inside-...

Eli Lilly to acquire gene-editing therapy developer Verve Therapeutics for up to $1.3 billion, companies say Eli Lilly will acquire Verve Therapeutics for up to $1.3 billion, the companies said on Tuesday.

Eli Lilly to acquire gene-editing therapy developer Verve Therapeutics for up to $1.3 billion, companies say reut.rs/4jWP3LH

Atul Butte died yesterday.
The world lost a giant.
A big bear of a man.
With a huge smile.
With love for everyone.
With energy that could power a room.
I loved everything about Atul.
I loved how he was always happy.
I loved how excited he was about science and helping people.

Wow!! Big thanks for the very lovely preview!! 🫶🫶🫶

TOO MANY analyses -> very DIFFERENT feedback on (several of) our submissions - some thought it was too lengthy, others considered the design creative, rigorous.

Perhaps no need to do standard analyses if the data/question itself is not standard...

Effects of parental autoimmune diseases on type 1 diabetes in offspring can be partially explained by HLA and non-HLA polymorphisms Leveraging Finnish nationwide multi-generational registers and the biobanks of FinnGen, Wang, Liu, et al. investigated the effect of parental autoimmune diseases on offspring T1D. Their creative and r...

@agacita.bsky.social & I preview: "Parental autoimmunity genetics & offspring T1D risk" www.cell.com/cell-genomic... for new #CellGenomics study: "Effects of parental autoimmune diseases on T1D in offspring can be partially explained by HLA & non-HLA polymorphisms" www.cell.com/cell-genomic...

Great talk @j-a-mitchell.bsky.social!

SLEEP 2025 | APSS Annual Meeting | AASM | SRS SLEEP is the premier conference dedicated to clinical sleep medicine, sleep and circadian research, and sleep health.

Check out my @chopresearch.bsky.social colleague (& fellow Scot!), @j-a-mitchell.bsky.social's #SLEEP2025 talk this afternoon: "Actigraphy-Estimated Rest-Activity Rhythm Characteristics of Adolescents by Socio-Demographic Factors" - covering work by Misol Kwon. 2.30pm, Room 619
www.sleepmeeting.org

Looking forward to presenting at the Trainee Symposium this morning at #SLEEP2025 here in beautiful Seattle - together with Hanna Ollila and Brittany Bush. Come on by! "Genetic Insights into Sleep Disorders" session - 9.10am Room 212.

www.sleepmeeting.org/schedule/hig...

Check out @maxdudek.bsky.social paper on fpQTLs!

www.cell.com/ajhg/fulltex...

Delighted to contribute, along with locally @adwellspenn.bsky.social & @alessandrachesi.bsky.social‬. "Mapping chromatin interactions at melanoma susceptibility loci uncovers distant cis-regulatory gene targets" @chopresearch.bsky.social @penngenetics.bsky.social
authors.elsevier.com/c/1l8KggeXDz0y

Go Spurs! Great to see them win a trophy after all the years of drought. I’m sure the press room will be busier than when I was there as a tourist 🤣

No better way to celebrate 10 years(!!) since joining the Grant lab than to celebrate at my PhD graduation! @struangrant.bsky.social I am so grateful for all the years of mentorship, and I’m so excited to continue collaborating with you and the rest of our colleagues at Penn/CHOP for years to come!

Dr. Rebecca Ahrens-Nicklas

In a landmark scientific feat published in NEJM, a CHOP & Penn Medicine team treated the first patient with personalized #genetherapy, designed uniquely for newborn KJ, who was diagnosed with a rare #ureacycledisorder at birth. Learn more: http://ms.spr.ly/63327Sw92F

Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease | NEJM Base editors can correct disease-causing genetic variants. After a neonate had received a diagnosis of severe carbamoyl-phosphate synthetase 1 deficiency, a disease with an estimated 50% mortality ...

www.nejm.org/doi/full/10....

Baby Is Healed With World’s First Personalized Gene-Editing Treatment

Congratulations to @ahrensnicklas.bsky.social, @kiranmusunuru.bsky.social and their collaborators!

www.nytimes.com/2025/05/15/h...

Philly's Amber Zimmerman wins the #BroadStreetRun for a second year in a row on the women's side, finishing in 54:01.81.