Discovery of novel cancer targets using functional genomics
Advances in CRISPR/Cas9 technologies have enabled large-scale multiplexed genetic screening for novel therapeutic targets and genetic interaction mapping across many contexts. We use genome-wide CRISPR screens and in vivo perturb-seq to identify and characterize targets that render tumors more sensitive to treatment such as chemotherapy or radiation therapy.
Related publications
Liu, S.J., Zou, C., Pak, J. et al. In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma. Genome Biol 25, 256 (2024). https://doi.org/10.1186/s13059-024-03404-6 https://genomebiology.biomedcentral.com/articles/10.1186/s13059-024-03404-6
Liu, S.J., Casey-Clyde, T., Cho, N.W. et al. Epigenetic reprogramming shapes the cellular landscape of schwannoma. Nat Commun 15, 476 (2024). https://doi.org/10.1038/s41467-023-40408-5 https://www.nature.com/articles/s41467-023-40408-5
Liu, S.J., Malatesta, M., Lien, B.V. et al. CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma. Genome Biol 21, 83 (2020). https://doi.org/10.1186/s13059-020-01995-4 https://genomebiology.biomedcentral.com/articles/10.1186/s13059-020-01995-4
Liu SJ, Horlbeck MA, Cho SW, Birk HS, Malatesta M, He D, Attenello FJ, Villalta JE, Cho MY, Chen Y, Mandegar MA, Olvera MP, Gilbert LA, Conklin BR, Chang HY, Weissman JS, Lim DA. CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells. Science. 2017 Jan 6;355(6320):aah7111. doi: 10.1126/science.aah7111. Epub 2016 Dec 15. PMID: 27980086; PMCID: PMC5394926. https://www.science.org/doi/10.1126/science.aah7111
Role of DNA damage response in radiation treatment resistance
The ability of cancer cells to repair DNA damage caused by radiation therapy is major barrier to effective treatments for patients with brain tumors. We are interested in targeting known and novel vulnerabilities in the DNA damage response to improve therapeutics against brain tumors such as adult and pediatric glioblastomas, among the deadliest primary brain tumors.
Related publications
Liu, S.J., Malatesta, M., Lien, B.V. et al. CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma. Genome Biol 21, 83 (2020). https://doi.org/10.1186/s13059-020-01995-4 https://genomebiology.biomedcentral.com/articles/10.1186/s13059-020-01995-4
Epigenetic engineering as novel precision therapeutics for cancer
Engineered CRISPR/Cas9 systems enable control of gene expression and epigenetic state in cells and tumors. We develop epigenetic editing strategies for in vivo applications in oncology to understand and exploit the role of epigenetics in tumor progression and treatment resistance.
Related publications
K Lin, L Goudy, J Pak, K Foster, E Payne, T Ozawa, J de Groot, H Vasudevan, D Raleigh, LA Gilbert, MS Berger, SJ Liu. CRISPR-Based Epigenome Editing and Genome Wide Screening Define Mediators of Chemotherapy Response in Glioblastoma. International Journal of Radiation Oncology, Biology, Physics. 117, 2 (2023). https://doi.org/10.1016/j.ijrobp.2023.06.316 https://www.redjournal.org/article/S0360-3016(23)04750-8/fulltext