John Liu, MD, PhD
Asst Professor in Residence
Radiation Oncology
School of Medicine

1) 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.

2) 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.

3) 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.

• Proteasome inhibition for glioblastoma: Lessons learned and new opportunities.
  Neuro-oncology 2024 Liu SJ, Raleigh DR, de Groot JF
• CRISPRi screens identify the lncRNA, LOUP, as a multifunctional locus regulating macrophage differentiation and inflammatory signaling.
  Proceedings of the National Academy of Sciences of the United States of America 2024 Halasz H, Malekos E, Covarrubias S, Yitiz S, Montano C, Sudek L, Katzman S, Liu SJ, Horlbeck MA, Namvar L, Weissman JS, Carpenter S
• Spatial genomic, biochemical and cellular mechanisms underlying meningioma heterogeneity and evolution.
  Nature genetics 2024 Lucas CG, Mirchia K, Seo K, Najem H, Chen WC, Zakimi N, Foster K, Eaton CD, Cady MA, Choudhury A, Liu SJ, Phillips JJ, Magill ST, Horbinski CM, Solomon DA, Perry A, Vasudevan HN, Heimberger AB, …
• Hypoxia-informed RBE-weighted beam orientation optimization for intensity modulated proton therapy.
  Medical physics 2024 Ramesh P, Ruan D, Liu SJ, Seo Y, Braunstein S, Sheng K
• Epigenetic reprogramming shapes the cellular landscape of schwannoma.
  Nature communications 2024 Liu SJ, Casey-Clyde T, Cho NW, Swinderman J, Pekmezci M, Dougherty MC, Foster K, Chen WC, Villanueva-Meyer JE, Swaney DL, Vasudevan HN, Choudhury A, Pak J, Breshears JD, Lang UE, Eaton CD, Hiam-Galvez…
• Spatial genomic, biochemical, and cellular mechanisms drive meningioma heterogeneity and evolution.
  Research square 2023 Lucas CH, Mirchia K, Seo K, Najem H, Chen W, Zakimi N, Choudhury A, Liu SJ, Phillips J, Magill S, Horbinski C, Solomon D, Perry A, Vasudevan H, Heimberger A, Raleigh D
• MerlinS13 phosphorylation controls meningioma Wnt signaling and magnetic resonance imaging features.
  Research square 2023 Eaton C, Avalos L, Liu SJ, Casey-Clyde T, Bisignano P, Lucas CH, Stevenson E, Choudhury A, Vasudevan H, Magill S, Krogan N, Villanueva-Meyer J, Swaney D, Raleigh D
• Dual genome-wide coding and lncRNA screens in neural induction of induced pluripotent stem cells.
  Cell genomics 2022 Wu D, Poddar A, Ninou E, Hwang E, Cole MA, Liu SJ, Horlbeck MA, Chen J, Replogle JM, Carosso GA, Eng NWL, Chang J, Shen Y, Weissman JS, Lim DA
• Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities.
  Nature genetics 2022 Choudhury A, Magill ST, Eaton CD, Prager BC, Chen WC, Cady MA, Seo K, Lucas CG, Casey-Clyde TJ, Vasudevan HN, Liu SJ, Villanueva-Meyer JE, Lam TC, Pu JK, Li LF, Leung GK, Swaney DL, Zhang MY, Chan JW,…
• Resection with intraoperative cesium-131 brachytherapy as salvage therapy for recurrent brain tumors.
  Journal of neurosurgery 2022 Chen WC, Lafreniere M, Phuong C, Liu SJ, Baal JD, Lometti M, Morin O, Ziemer B, Vasudevan HN, Lucas CG, Hervey-Jumper SL, Theodosopoulos PV, Magill ST, Fogh S, Nakamura JL, Boreta L, Sneed PK, …
• Long noncoding RNAs in cancer metastasis.
  Nature reviews. Cancer 2021 Liu SJ, Dang HX, Lim DA, Feng FY, Maher CA
• miRNA-independent function of long noncoding pri-miRNA loci.
  Proceedings of the National Academy of Sciences of the United States of America 2021 He D, Wu D, Muller S, Wang L, Saha P, Ahanger SH, Liu SJ, Cui M, Hong SJ, Jain M, Olson HE, Akeson M, Costello JF, Diaz A, Lim DA
• Genome-Scale Perturbation of Long Noncoding RNA Expression Using CRISPR Interference.
  Methods in molecular biology (Clifton, N.J.) 2021 Liu SJ, Horlbeck MA, Weissman JS, Lim DA
• CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma.
  Genome biology 2020 Liu SJ, Malatesta M, Lien BV, Saha P, Thombare SS, Hong SJ, Pedraza L, Koontz M, Seo K, Horlbeck MA, He D, Birk HS, Jain M, Olsen HE, Akeson M, Weissman JS, Monje M, Gupta N, Raleigh DR, Ullian EM, …
• Fitness effects of CRISPR/Cas9-targeting of long noncoding RNA genes.
  Nature biotechnology 2020 Horlbeck MA, Liu SJ, Chang HY, Lim DA, Weissman JS
• Multiplatform Molecular Profiling Reveals Epigenomic Intratumor Heterogeneity in Ependymoma.
  Cell reports 2020 Liu SJ, Magill ST, Vasudevan HN, Hilz S, Villanueva-Meyer JE, Lastella S, Daggubati V, Spatz J, Choudhury A, Orr BA, Demaree B, Seo K, Ferris SP, Abate AR, Oberheim Bush NA, Bollen AW, McDermott MW, …
• Outer Radial Glia-like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma.
  Cell stem cell 2020 Bhaduri A, Di Lullo E, Jung D, Müller S, Crouch EE, Espinosa CS, Ozawa T, Alvarado B, Spatazza J, Cadwell CR, Wilkins G, Velmeshev D, Liu SJ, Malatesta M, Andrews MG, Mostajo-Radji MA, Huang EJ, …
• The Long Noncoding RNA Pnky Is a Trans-acting Regulator of Cortical Development In Vivo.
  Developmental cell 2019 Andersen RE, Hong SJ, Lim JJ, Cui M, Harpur BA, Hwang E, Delgado RN, Ramos AD, Liu SJ, Blencowe BJ, Lim DA
• Modulating the expression of long non-coding RNAs for functional studies.
  EMBO reports 2018 Liu SJ, Lim DA
• Reirradiation and PD-1 inhibition with nivolumab for the treatment of recurrent diffuse intrinsic pontine glioma: a single-institution experience.
  Journal of neuro-oncology 2018 Kline C, Liu SJ, Duriseti S, Banerjee A, Nicolaides T, Raber S, Gupta N, Haas-Kogan D, Braunstein S, Mueller S
• Promoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element.
  Cell 2018 Cho SW, Xu J, Sun R, Mumbach MR, Carter AC, Chen YG, Yost KE, Kim J, He J, Nevins SA, Chin SF, Caldas C, Liu SJ, Horlbeck MA, Lim DA, Weissman JS, Curtis C, Chang HY
• Single-cell profiling of human gliomas reveals macrophage ontogeny as a basis for regional differences in macrophage activation in the tumor microenvironment.
  Genome biology 2017 Müller S, Kohanbash G, Liu SJ, Alvarado B, Carrera D, Bhaduri A, Watchmaker PB, Yagnik G, Di Lullo E, Malatesta M, Amankulor NM, Kriegstein AR, Lim DA, Aghi M, Okada H, Diaz A
• Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex.
  Science (New York, N.Y.) 2017 Nowakowski TJ, Bhaduri A, Pollen AA, Alvarado B, Mostajo-Radji MA, Di Lullo E, Haeussler M, Sandoval-Espinosa C, Liu SJ, Velmeshev D, Ounadjela JR, Shuga J, Wang X, Lim DA, West JA, Leyrat AA, Kent WJ…
• CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells.
  Science (New York, N.Y.) 2016 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
• Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas.
  Molecular systems biology 2016 Müller S, Liu SJ, Di Lullo E, Malatesta M, Pollen AA, Nowakowski TJ, Kohanbash G, Aghi M, Kriegstein AR, Lim DA, Diaz A
• Single-cell analysis of long non-coding RNAs in the developing human neocortex.
  Genome biology 2016 Liu SJ, Nowakowski TJ, Pollen AA, Lui JH, Horlbeck MA, Attenello FJ, He D, Weissman JS, Kriegstein AR, Diaz AA, Lim DA
• Molecular identity of human outer radial glia during cortical development.
  Cell 2015 Pollen AA, Nowakowski TJ, Chen J, Retallack H, Sandoval-Espinosa C, Nicholas CR, Shuga J, Liu SJ, Oldham MC, Diaz A, Lim DA, Leyrat AA, West JA, Kriegstein AR
• The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells.
  Cell stem cell 2015 Ramos AD, Andersen RE, Liu SJ, Nowakowski TJ, Hong SJ, Gertz C, Salinas RD, Zarabi H, Kriegstein AR, Lim DA
• Activation of neuronal gene expression by the JMJD3 demethylase is required for postnatal and adult brain neurogenesis.
  Cell reports 2014 Park DH, Hong SJ, Salinas RD, Liu SJ, Sun SW, Sgualdino J, Testa G, Matzuk MM, Iwamori N, Lim DA
• Pluripotency factors in embryonic stem cells regulate differentiation into germ layers.
  Cell 2011 Thomson M, Liu SJ, Zou LN, Smith Z, Meissner A, Ramanathan S
• Logic integration of mRNA signals by an RNAi-based molecular computer.
  Nucleic acids research 2010 Xie Z, Liu SJ, Bleris L, Benenson Y