Noonan Lab

Very sad news. David Botstein made enormous contributions to molecular biology & genetics. I first met him in a grad school interview. I learned something from him each of the few times I saw him since. Indelible personality. Here he is giving a keynote at the 2015 UCSD Genetics Retreat.

I was sad to learn that my postdoctoral mentor, David Botstein, died yesterday. I started with David as a postdoc in 1998, and he had a profound effect on both my life and scientific career. He was a giant in the field of genetics, making seminal contributions in both yeast and human genetics. 1/

Committee Releases Conferenced Defense, Homeland Security, Labor, Health and Human Services, Education, and Related Agencies, and Transportation, Housing and Urban Development, and Related Agencies Bi... United States Senate Committee on Appropriations

The conference (agreement between House and Senate) appropriations bill that includes HHS and NIH was released this morning.

www.appropriations.senate.gov/news/majorit...

1/5

NIH budget bill out today.

It’s the result of heavy negotiations in Congress over past month+. 🧪

Big pic: NIH budget now is abt more than funding. It’s abt restraining the technical ways NIH is being broken by Proj 2025. And the restraints in the bill are tepid 🤷‍♂️

Also: watch ICE/DHS budget.
🧵1/

Cancer research costs too much but we have the money to run Venezuela

We're truly in the darkest timeline.
bsky.app/profile/timb...

I really hate it when scientists keep saying that “we need to rebuild trust in science,” because it implies that scientists are to blame for the mistrust rather than the millions of dollars of dark money that have funded political attacks on science in order to advance a far right agenda.

We didn't investigate behavioral phenotypes in our model. However our collaborator Rebecca Muhle is studying that question so keep an eye out for results from her group.

Thanks to the SFARI, @simonsfoundation.org, NOMIS Foundation, NICHD, NIGMS, NIMH, Charles H Hood Foundation, and NSF for supporting this work and making this paper possible!

Cell type-specific dysregulation of gene expression due to Chd8 haploinsufficiency during mouse cortical development Disruptive variants in the chromodomain helicase CHD8 , which acts as a transcriptional regulator during neurodevelopment, are strongly associated with risk for autism spectrum disorder (ASD). Loss of...

This paper has been a massive undertaking, as can be appreciated by the changes between the published paper and our original preprint: doi.org/10.1101/2024...

Thanks to @krishnaswamylab.bsky.social and David van Dijk (@vandijklab.bsky.social), who developed a core method in the paper, PHATE, and helped with data analysis in the early phases of the project.

Congratulations to lead authors Kristi Yim, Marybeth Baumgartner (@baumoflife.bsky.social), and Martina Krenzer, in addition to co-authors María Rosales Larios, Mina Hill-Terán, Tim Nottoli, and @rebeccamuhle.bsky.social for their impressive work and perseverance on this project!

These findings suggest that CHD8 loss of function impacts gene regulatory networks and neurogenic potential of early radial glia, with distinct impacts on synaptic development and synaptic signaling of maturing excitatory neurons later in cortical development.

Across excitatory neuron subtypes of the maturing cortex, we detected dysregulation of synaptogenesis, synaptic organization, and synaptic signaling genes, indicative of synaptic immaturity or synaptogenic delay due to CHD8 loss of function.

In radial glia of the early embryonic cortex, genes associated with risk for neurodevelopmental disorders and genes involved in chromatin remodeling, neuron projection development, and migration were downregulated.

CHD8 loss of function had cell-type-biased impacts in the developing mouse cortex, which were dynamic across development. There were distinct signatures in early radial glia, the primary progenitor cell type of the cortex, and in maturing excitatory neurons.

We found that Chd8 and other ASD risk-associated genes had convergent expression patterns that were conserved between the mouse and human developing cortex, with expression peaking in differentiating neurons.

We developed a mouse model of CHD8 loss of function and performed the first published single-cell transcriptomics analysis of the impacts of CHD8 loss of function across mouse cortical development.

Loss-of-function variants in CHD8 are strongly associated with risk of autism spectrum disorder (ASD) and macrocephaly. Previous studies, including work from our lab, implicated CHD8 in broad gene regulation during neurodevelopment, including the direct regulation of other ASD risk-associated genes.

Cell-type-specific dysregulation of gene expression due to Chd8 haploinsufficiency during mouse cortical development Yim et al. use single-cell transcriptomics to elucidate the molecular outcomes of Chd8 haploinsufficiency in the mouse cortex. Their results provide insight into dynamic, cell-type-biased transcriptio...

Out in Cell Genomics: A comprehensive analysis of the cell-type-specific effects of CHD8 loss of function on gene expression in the embryonic and juvenile mouse cortex. Thread 🧵:
www.cell.com/cell-genomic...

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...

Human Genome Sciences The overall goal of the Human Genome Sciences (HGS) track is to train the next generation of scientists in the areas of human genomics, genetics, and

Yale has established a new PhD program in Human Genome Sciences and will be accepting applications this fall. We are also searching for an Associate Director of Student Services (a PhD-level position).

Learn more here:
medicine.yale.edu/bbs/tracks/h...

careers.yale.edu/us/en/job/YU...

Check out our latest work co-led by @dcsoto.bsky.social and @jmuribescr.bsky.social identifying hundreds of human duplicated gene families using the new T2T-CHM13 assembly, with a focus on those potentially contributing to brain evolution 🧪: authors.elsevier.com/a/1lTQtL7PXu...

So NIMH is no longer supporting F31s, but is still supporting F30s and F32s? I initially thought this might be an error in the FOA (there are a lot more errors popping up now), but it's in the Guide too:
grants.nih.gov/funding/nih-...

After spending tons of time rebutting our trainee's grant termination.. this response doesn't suggest a 'careful assessment'

There aren't mechanisms that support mid-PhD trainees, so theres nothing to apply to, even though it scored in the top % of all apps.
Not to mention the demotivation.
Ugh.

Yale backing Harvard in lawsuit against government In a joint motion with 17 other universities, Yale argues that cutting federal funds to Harvard endangers the nation.

I'm proud of Yale for doing this

Great article, Caleb! Thanks for writing about our work.

Hybrid brains and the search for what makes us human - the Node It lives. It lives! What lives, you may ask? Well, somewhere in a lab at Yale University, one young scientist has stuck human brain cells and chimp brain

Hey BlueSky! Want to learn more about some almost literally mind-bending brain research being done by @noonanlab.bsky.social?

Check out the story below for one scientist's perspective on the importance of basic scientific research and the pursuit of open-ended questions about what makes us human.

A human-specific enhancer fine-tunes radial glia potency and corticogenesis - Nature HARE5, a human accelerated region enhancer, modulates cortical development by influencing neural progenitor cell behaviour, leading to an enlarged neocortex with increased functional independence betw...

Thrilled to share our latest study out in @natureportfolio.nature.com led by the fantastically talented Jing Liu. Our study provides insight into a long standing question in biology: What molecular features make us uniquely human and how do these function? www.nature.com/articles/s41...

Harvard Leaders See Only Bad Outcomes Ahead as They Battle Trump

Despite the Times trying to spin this as “Harvard should quit,” the article really (and likely unintentionally) conveys the message “Harvard should absolutely keep fighting.”

www.nytimes.com/2025/05/08/u...