Co-Mentor: Brant Peterson, PhD
Cambridge, Massachusetts, United States
Our goal is to genetically dissect the genes and regulatory elements that are critical for human neuronal function in an effort to identify novel targets to modulate neurological disease. In neuroscience, identifying new targets by high-throughput screening has been difficult because of limited access to human neurons and the inability to rapidly perturb neuronal genomes. To enable high-throughput genetic screening in disease relevant cell types, our group has developed methods for generating large batches of human neurons derived from pluripotent stem cells with disease mutations, and genome engineering machinery. Furthermore, we utilize cerebral organoids to capture the relevant cellular diversity and spatial organization to study the genetic basis of neurodevelopmental disorders. Lastly, we generate high-dimensional phenotypes using miniaturized well-based and single cell RNA sequencing to interrogate both cellular identity and transcriptome-wide responses to genetic and chemical perturbation using cutting-edge computational techniques.
DRUG-seq for miniaturized high-throughput transcriptome profiling in drug discovery.
Ye C, Ho DJ, Neri M, Yang C, Kulkarni T, Randhawa R, Henault M, Mostacci N,
Farmer P, Renner S, Ihry R, Mansur L, Keller CG, McAllister G, Hild M, Jenkins J,
Kaykas A Nat Commun. 2018 Oct 17;9(1):4307.
p53 inhibits CRISPR-Cas9 engineering in human pluripotent stem cells.
Ihry RJ, Worringer KA, Salick MR, Frias E, Ho D, Theriault K, Kommineni S,
Chen J, Sondey M, Ye C, Randhawa R, Kulkarni T, Yang Z, McAllister G, Russ C,
Reece-Hoyes J, Forrester W, Hoffman GR, Dolmetsch R, Kaykas A.
Nat Med. 2018 Jul;24(7):939-946.
Genetic Ablation of AXL Does Not Protect Human Neural Progenitor Cells and Cerebral Organoids from Zika Virus Infection.
Wells MF, Salick MR, Wiskow O, Ho DJ, Worringer KA, Ihry RJ, Kommineni S,
Bilican B, Klim JR, Hill EJ, Kane LT, Ye C, Kaykas A, Eggan K.
Cell Stem Cell. 2016 Dec 1;19(6):703-708.
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