Although this particular variant may only explain a fraction of human pathologogy, its downstream impacts on neuronal structure via RhoA-GEF make it a useful system for connecting convergent molecular, structural, and functional phenotypes.
Excited to share our preprint! Impressive effort from grad student Anna Rader Groves and co-author @cgalli-io.bsky.social, in collaboration with Melanie Grubisha and Robert Sweet (PITT). @grubisha
Anna joined my lab at the peak of covid, but quickly gathered data, coauthored key publications, and wrote a book chapter. On her first F31 submission, she scored a 2nd percentile (which was subsequently awarded).
Both dendrite loss and reduced mismatch negativity are pronounced in numerous neuropsychiatric disorders. Correlating these observations in patient samples only gets us so far. Animal models provide a controlled system to understand how distinct features causally connect.
A little background: KalrnPT is a rare variant affiecting the kal-9 isoform of kalirin — a key regulator of dendrite and spine morphology via the Rac and RhoA.
This occurred against a backdrop of normal feature selectivity and firing rates in V1, as well as unaffected dendritic structure in other layers of V1.
This year, she wrapped up her two studies (one linking genes to dendrite loss and mismatch responses; one focused on the development of mismatch responses in adolescence) which are preprints and currently under review. www.biorxiv.org/content/10.1... and … . www.biorxiv.org/content/10.6...
Huge congrats to my grad student, Dr. Anna Rader Groves, who successfully defended her disseratation last week! I consider myself lucky to have mentored Anna over the past 5 years.
We report co-occurring dendrite loss and sensory integration (visual mismatch responses) specific to supragranular (layer 2/3) neurons in visual cortex due to a missense mutation affecting Kalirin (KalPT) -- and specifically, the kal9 isoform.
Anna has accepted at job at SURA in DC as a senior policy advisor. I feel honored to have worked with her.
sura.org
I don’t think I can overstate her potential. For those of you who don't know Dr. Rader Groves, I don't really know where to begin... but imagine if Leslie Knope was a scientist.
