Nadav Ahituv

Most neurodevelopmental disorders are caused by having 1 functional gene copy. Using SCN2A, we show that upregulating the functional copy rescues neuronal phenotypes. Amazing work with @neurobender.bsky.social led by Serena Tamura, Andrew Nelson, Perry Spratt & others.
www.nature.com/articles/s41...

We are excited to inform you about the annual UCSF IHG Genotech Symposium, taking place on 9/22. The goal of this symposium is to foster collaboration and cross-fertilization between industry and academia in genetics and genomics. Hope to see you there!
genotech.ucsf.edu/home

NIPBL dosage shapes genome folding by tuning the rate of cohesin loop extrusion Cohesin loop extrusion is a major driver of chromosome folding, but how its dynamics are controlled to shape the genome remains elusive. Here we disentangle the contributions of the cohesin cofactors ...

New preprint with @gfudenberg.bsky.social

We find the rate of cohesin loop extrusion in cells is set by NIPBL dosage and tunes many aspects of chromosome folding.

This provides a molecular basis for NIPBL haploinsufficiency in humans. 🧵👇

www.biorxiv.org/content/10.1...

Leveraging sequences missing from the human genome to diagnose cancer - Communications Medicine Georgakopoulos-Soares, Yizhar-Barnea, Mouratidis et al. identify neomers, short (16 base pair) DNA sequences that are absent in the genomes of healthy individuals but appear in tumors due to mutations...

Neomers are short 16bp sequences missing in our genome. Cancer causes mutations, leading to their appearance, making them a great diagnostic tool from cell-free DNA. Amazing work by Ilias Georgakopoulos-Soares, Ofer Yizhar-Barnea, Ioannis Mouratidis, Martin Hemberg...
www.nature.com/articles/s43...

Our protocol on growing adipocytes or adipose organoids for Adipose Manipulation Transplantation (AMT), by the amazing Kelly An and Yusuke Ito, is out in Bio-Protocol. Hoping it will be helpful in the adoption of this therapeutic technology for various conditions.

bio-protocol.org/en/bpdetail?...

Image of an old building in Oxford with the heading 'postdoc opportunities' and the text 'computational approaches to improve rare disease diagnosis and treatment' and 'Big Data Institute, University of Oxford'

📣 We are recruiting! Please share!!

Are you a bioinformatician / computational scientist who wants to apply your skills to understanding regulatory biology and improving rare disease diagnosis and treatment? 🧠 💻 🧬 🩺

We have two roles available 👇

🧵 1/4

Group Leader - Genome Biology Unit Are you ready to lead groundbreaking research in Genome Biology? Join us at EMBL! We are seeking a motivated scientist to lead an independent research group addressing exciting and original biological...

To all post-docs: The Genome Biology dept ‪@embl.org
has an Independent faculty position. Fantastic place to set up your lab –great package: core funding, fantastic Ph.D. students, cutting edge core facilities & great colleagues. Closing date Sept 19th
embl.wd103.myworkdayjobs.com/en-US/EMBL/j...

Predicting the direction of phenotypic difference Nature Communications - Here authors reveal a method to predict key information on phenotypes - their direction. This is achievable even for phenotypes with incomplete genotype-to-phenotype...

Given two genomes, can you tell who’s taller or more prone to a disease? How confident can you be? A fresh take on phenotypic inference, now out:
rdcu.be/exW4f
See thread🧵👇:

Join us for our @ihgatucsf.bsky.social Genotech Symposium on September 22nd 9-6pm at our Mission Bay campus! We have a great lineup of speakers and registration is free.

genotech.ucsf.edu

תנחומי!

Simultaneous epigenomic profiling and regulatory activity measurement using e2MPRA Cis-regulatory elements (CREs) have a major effect on phenotypes including disease. They are identified in a genome-wide manner by analyzing the binding of transcription factors (TFs), various co-fact...

Lentivirus massively parallel reporter assays integrate & enrich for specific sequences in the genome. We utilize this to test their epigenetic modifications & open chromatin alongside their regulatory activity. Amazing work by Zicong Zhang, Fumitaka Inoue & others.
www.biorxiv.org/content/10.1...

Capture-C MPRA: A high-throughput method to simultaneously characterize promoter interactions and regulatory activity Cis regulatory elements (CREs) interact with their target promoters over long genomic distances and can be identified using chromatin conformation capture (3C) assays. Their regulatory activity can be...

Capture C identifies promoter interacting sequences. MPRA tests sequences for regulatory activity. Here, we combined them both to test sequences with their target promoter. Amazing work by @colinearnould.bsky.social, Pia Keukeleire, Martin Kircher and many others.
www.biorxiv.org/content/10.1...

Massively parallel reporter assays and mouse transgenic assays provide correlated and complementary information about neuronal enhancer activity - Nature Communications MPRAs and in vivo transgenic mouse assays are two potentially complementary ways to assay the impact of noncoding variants. Here, authors find a strong and specific correlation between the assays in n...

Comparison between a neuronal massively parallel reporter assay for 50,000 sequences and 20,000 variants with mouse enhancer assays provide complimentary information. Great work by Michael Kosicki, Dianne Laboy Cintrón, Len Pennacchio, Martin Kircher lab & many others.
www.nature.com/articles/s41...

Massively parallel jumping assay decodes Alu retrotransposition activity - Nature Communications Here, the authors develop a high-throughput assay to measure the jumping potential of thousands of transposons in parallel.

Massively parallel jumping assay (MPJA) enables to test the jumping potential of thousands of transposons. Analysis of >160,000 Alu haplotypes identified transposition-asssociated domains. Amazing work by Navneet Matharu, Jingjing Zhao, Martin Kircher and many others.
www.nature.com/articles/s41...

MPRAbase (mprabase.ucsf.edu) , a customized database for massively parallel reporter assays (MPRAs) to easily find and download MPRA data. Amazing work by Jingjing Zhao, Fotis Baltoumas, Georgios Pavlopoulos, @vagar.bsky.social, ilias Georgakopoulos-Soares & others.

genome.cshlp.org/content/earl...

One of the toughest parts of the field of massively parallel reporter assays to measure >~thousands of elements is that there are hundreds of pubs using them, but no central repo to easily locate the results....until now! Great collab w/ Jingjing Zhao, Ilias G-S, and @nadavahituv.bsky.social!!

From bats to cancer – the power of gene regulation | Speaking of Mol Bio Dr. Nadav Ahituv, Professor and Director of the Institute for Human Genetics at UCSF, takes us on a journey through groundbreaking work in gene regulation, disease genetics, and the evolution of bats....

Was a lot of fun doing this podcast! Thanks @thermofishersci.bsky.social team!

speaking-of-mol-bio.simplecast.com/episodes/fro...

Reversible histone deacetylase activity catalyzes lysine acylation - Nature Chemical Biology Tsusaka et al. discover that histone deacetylases, which are well known to remove protein modifications, such as lysine acetylation and β-hydroxybutyrylation, can also reverse their chemical activity ...

I could not be more excited to have our lab's first story online where we report our discovery that HDACs ~reverse~ their activity to ADD acyl groups to lysine! We found this for our favorite ketone body, BHB, but this pathway controls other lysine modifications too!🧵

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

Genetically Modified Fat Cells Starve Tumors in Mice White fat cells genetically engineered to aggressively consume glucose and other nutrients can shrink tumors in mice, a new study has found.

Nice story about our adipose manipulation transplantation (AMT) cancer therapy written by Edward Winstead at NCI.
www.cancer.gov/news-events/...

Looking forward to this symopium in honor of Ray White. There is still time to register.

Fighting cancer with fat

#ResearchHighlight 🚨
@nadavahituv.bsky.social &Co developed a new therapeutic approach, adipose manipulation transplantation (AMT), in which engineered adipocytes are used to outcompete tumours for lipids and glucose to suppress cancer progression.
👀 ⬇️

Looking for a new director for our Genetic Counseling Program at UCSF. Job ad below and feel free to contact me directly with any questions.
sjobs.brassring.com/TGnewUI/Sear...

Looking forward to this meeting!

Sri, if there is anyone at UCSF that could be helpful let me know. Happy to help in any way.

Starving tumors with fat - Nature Biotechnology Adipocytes can be isolated, genetically manipulated, and then reimplanted. In this study, these properties were leveraged to engineer adipocytes that can outcompete tumors for essential metabolic reso...

Research Briefing on this article
www.nature.com/articles/s41...

Implantation of engineered adipocytes suppresses tumor progression in cancer models - Nature Biotechnology Adipose manipulation transplantation can reduce tumor growth and proliferation in vitro and in mouse models.

Tumors need a lot of nutrients to grow. By engineering and implanting fat cells to outcompete cancers for nutrients we can suppress them. Novel cancer therapy called Adipose Manipulation Transplantation (AMT). AMAZING work led by and dedicated to Hai Nguyen.
www.nature.com/articles/s41...

Beware! AAV libraries prone to length & homology dependent chimerism! Our latest preprint, from the brilliant @jblalanne.bsky.social‬, was a true surprise as related phenomena are textbook for lentivirus (highly relevant to HIV & Perturb-seq) yet to our reading not known for AAV tinyurl.com/5amc562a

Massively parallel characterization of transcriptional regulatory elements - Nature Lentivirus-based reporter assays for 680,000 regulatory sequences from three cell lines coupled to machine-learning models lead to insights into the grammar of cis-regulatory elements.

Super excited to announce our latest work. On a personal note, it's not an exaggeration to say that blood, sweat, and tears got us to the finish line on this: working w/ an outstanding global team of scientists in Germany, Japan, Russia, and USA responding in >100 pages of complex reviewer comments.

Massively parallel characterization of transcriptional regulatory elements - Nature Lentivirus-based reporter assays for 680,000 regulatory sequences from three cell lines coupled to machine-learning models lead to insights into the grammar of cis-regulatory elements.

Massively parallel reporter assays (MPRAs) testing >680,000 sequences combined with machine learning to improve regulatory element & variant effect prediction. Amazing work by @vagar.bsky.social, Fumitaka Inoue, @jshendure.bsky.social and many others as part of ENCODE.
www.nature.com/articles/s41...

Seven Scientific Discoveries From 2024 That Could Lead to New Inventions From indestructible tardigrades to body-merging comb jellies, animals can teach humans so much about medicine, robotics, aging and survival

Extremely excited to see that our work on how fruit bats can eat so much sugar without getting diabetes is one of the seven on this list!
www.smithsonianmag.com/innovation/s...