Kadir Akdemir

Kim Lab at UC Irvine Visit the post for more.

The Kim Lab (sskimlab.org) at UC Irvine is recruiting motivated grad students interested in uncovering how transcriptional regulators direct cell fates. We accept students through the CMB (cmb.uci.edu) and MCSB (ccbs.uci.edu/education/mcsb/) PhD programs. Please share with prospective grad students!

More than 30% of this century’s science Nobel prizewinners immigrated: see their journeys The most common destination for eventual Nobel laureates in physics, chemistry and medicine since 2000 is the United States, Nature has found.

Less than 70% of science Nobel prize winners awarded this century hail from the country in which they were awarded their prize.
“Mobility benefits everyone. Each newcomer brings fresh ideas, new techniques & different ways of looking at old problems”
🧪 #academicSky
www.nature.com/articles/d41...

Very happy that the review article by @magnushaughey.bsky.social and Imran Noorani on the evolutionary role of extra-chromosomal DNA in cancers just came out.

authors.elsevier.com/sd/article/S...

Decoupling chromatin hubs from gene control Nature Structural & Molecular Biology - Chromatin hubs, which are formed during cell differentiation, are characterized by simultaneous interactions between multiple regulatory elements and...

🚨The formation of 3D chromatin hubs is a poorly understood
phenomenon.

I wrote a N&V about the excellent work Karpinska, Zhu and colleagues, from @mariekeoudelaar.bsky.social lab, who shed new light on the formation and function of these structures.

rdcu.be/elPt3

Thanks for reading and we would be delighted to hear your comments/suggestions.

I’m also incredibly proud of our multi-institutional, collaborative team—this work reflects the efforts of researchers across disciplines and career stages, including three undergraduate students who are co-authors on this study!

We are deeply grateful to all the patients and their families whose generosity made this study possible.

This supports the conclusion that joint Hi-C/ONT-based reconstructions yield more accurate structural predictions than those based solely on short-read WGS.

We compared ecDNA structure and transcription in two tumors: in P59, EGFR and CDK4 were predicted to be on separate ecDNAs; in P68, on the same ecDNA. Xenium data showed stronger EGFR-CDK4 expression correlation in P68 compared to p59.

We found that ecDNA+ tumors form nuclear EGFR transcriptional hubs.
EGFR FISH on post-Xenium slides showed >70% of these hubs localized to the nucleus and overlapped with EGFR copy number - unlike control gene FABP7 with similar expression but no hub formation.

We found that EGFR ecDNA tumors are hypoxic, mesenchymal-rich, and pericyte-enriched.

Given our comprehensive whole-genome sequnecing datasets, we compared the spatial organization of ecDNA vs Linear Amplification GBMs

We found that IDH-mutant gliomas frequently harbored inflammatory microglia expressing CX3CR1 specifically within AC-like malignant neighborhoods, rather than OPC-like niches—despite the OPC-like malignant cell state being more prevalent in IDH-mutant gliomas.

To investigate the spatial tumor microenvironment of our glioma samples, we applied a single-cell spatial transcriptomics approach (10x Xenium), generating 4.6 million cells and over 775 million transcripts.
We identified distinct cell states in IDH-wildtype vs mutant gliomas

We next asked whether treatment contributed to ecDNA loss in recurrences. Recurrent tumors arose from residual regions of the primary site, suggesting ecDNAs were spatially restricted subclones eliminated during initial surgery.

We also examined EGFR expression levels, which showed a marked reduction in the recurrent tumors. Similarly, single-nucleus whole-genome analysis revealed the disappearance of the focal amplification on chromosome 7, while clonal alterations were retained.

Hi-C and WGS data revealed the loss of ecDNA signals in recurrent tumor (P-12r1) while preserving other structural variations, such as chromothripsis on chr 3

We also identified two GBM patients (P12 and P29) in whom ecDNA molecules were not implicated in tumor recurrence and were absent in both subsequent surgical specimens.

Hi-C and long-read data were essential to improve ecDNA reconstructions.
For example, for p59, the short-read reconstruction suggested EGFR and CDK4 genes are on the same ecDNA circle.
However, Hi-C and ONT WGS-based reconstructions suggested these genes reside on two distinct circles.

🔹 Resolving ecDNA Structure and Function
We used short- and long-read whole-genome sequencing plus Hi-C to reconstruct complex extrachromosomal DNA (ecDNA) structures. This revealed:

Tumors can harbor multiple ecDNA circles with distinct oncogenes.

We performed an integrative multi-omic and spatial transcriptomic analysis of 93 gliomas, leveraging 449 unique specimens to uncover how oncogenic drivers reshape tumor architecture and the surrounding microenvironment in human gliomas.

Excited to share our latest manuscript www.biorxiv.org/content/10.1...
This was a great collaboration with Drs. Huse, Lang, @jesserdixon.bsky.social

Model figure - in EAC cancers, as chromosomal instability (CIN) increases, we found that a CIN-driven cGAS-dependent axis drives myeloid directed chemokine expression and recruitment of tumor-favoring myeloid populations

Incoming - new preprint alert from the Parkes lab led by @brunobeernaert.bsky.social Full bluetutorial follows! 1/ 11 www.biorxiv.org/content/10.1...

🧪 We’re Hiring: Lab Technician 🧪

I’m happy to share that our newly established Emmy Noether Group in Essen is looking for a Lab Technician to join our team!

🔗 Apply here: karriere.ume.de/job-finder/?...
📅 Start: At the earliest possible date
💻 Homepage: kocakavuklab.vercel.app/overview

Omg, this is super funny but also very painful!!!

that’s right

Huge opportunity for postdocs gearing up for an academic job search, hosted by @stanford-chemh.bsky.social @berkeleymcb.bsky.social and UCSF!

Associate or Senior Editor Nature Genetics and Nature Communication Job Title: Associate or Senior Editor Nature Genetics and Nature Communication Organisation: Nature Portfolio Location: New York/Philadelphia, Shanghai/Beijing, Madrid or Milan Application Deadline: A...

Nature Genetics is looking to hire a new editor!
Come join our team and help publish the most exciting research in genetics and genomics! Deadline is April 25th.
springernature.wd3.myworkdayjobs.com/en-US/Spring...

YouTube video by Johan Gibcus Rules of Engagement

Earnshaw, Goloborodko, Dekker & Mirny labs are excited to present our latest work, "Rules of engagement for condensins and cohesins guide mitotic chromosome formation" - now accepted!!
www.science.org/doi/10.1126/...
A short clip describing the key results:
www.youtube.com/watch?v=pmvO...

An in-depth survey of immunosuppressive myeloid cell heterogeneity in GBM Brandon Emanuel León, Defne Bayik; An in-depth survey of immunosuppressive myeloid cell heterogeneity in GBM, Neuro-Oncology, , noaf080, https://doi.org/10

Lookin for a good read in between experiments? Check out the commentary article in @neuroonc.bsky.social @dbayik.bsky.social and I wrote on an insightful study on myeloid cells in gliomas 🙂‍↔️ link here: academic.oup.com/neuro-oncolo...