Research Summary

The Liu Lab at UCSF is an interdisciplinary basic and translational research group dedicated to advancing new treatments for malignant brain tumors and understanding mechanisms of treatment resistance. We develop and apply cutting-edge functional genomic approaches collaboratively to achieve this mission. In particular:

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.

Research Funding

  • July 1, 2015 - June 30, 2017 - Regulation of neurogenesis by the novel long non-coding RNA Pnky , Principal Investigator . Sponsor: NIH, Sponsor Award ID: F30NS092319

Education

06/2024 - Radiation Oncology Residency, University of California, San Francisco
06/2020 - Internal Medicine Prelim, Kaiser Permanente
MD, 06/2019 - Medicine, University of California, San Francisco
PhD, 03/2017 - Biomedical Sciences, University of California, San Francisco
AB, 05/2011 - Chemical and Physical Biology, Harvard University

Honors & Awards

  • CRISPR Cures for Cancer Initiative Pilot Award, University of California, San Francisco, 2023-2024
  • Catalyst Award, University of California, San Francisco, 2022-2023
  • The Sontag Foundation Conquer Cancer Young Investigator Award, University of California, San Francisco, 2022-2023
  • BTC SPORE Career Enhancement Award, University of California, San Francisco, 2021-2022
  • ABR Holman Pathway, University of California, San Francisco, 2020-2024
  • RSNA Roentgen Resident/Fellow Research Award, University of California, San Francisco, 2020-2024

Selected Publications

  1. Casey-Clyde T, Liu SJ, Serrano JAC, Teng C, Jang YG, Vasudevan HN, Bush JO, Raleigh DR. Eed controls craniofacial osteoblast differentiation and mesenchymal proliferation from the neural crest. bioRxiv. 2024 Jul 12.  View on PubMed
  2. Halasz H, Malekos E, Covarrubias S, Yitiz S, Montano C, Sudek L, Katzman S, Liu SJ, Horlbeck MA, Namvar L, Weissman JS, Carpenter S. CRISPRi screens identify the lncRNA, LOUP, as a multifunctional locus regulating macrophage differentiation and inflammatory signaling. Proc Natl Acad Sci U S A. 2024 May 28; 121(22):e2322524121.  View on PubMed
  3. 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, Raleigh DR. Spatial genomic, biochemical and cellular mechanisms underlying meningioma heterogeneity and evolution. Nat Genet. 2024 Jun; 56(6):1121-1133.  View on PubMed
  4. Ramesh P, Ruan D, Liu SJ, Seo Y, Braunstein S, Sheng K. Hypoxia-informed RBE-weighted beam orientation optimization for intensity modulated proton therapy. Med Phys. 2024 Mar; 51(3):2320-2333.  View on PubMed
  5. 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 KJ, Stevenson E, Chen KH, Lien BV, Wu D, Braunstein SE, Sneed PK, Magill ST, Lim D, McDermott MW, Berger MS, Perry A, Krogan NJ, Hansen MR, Spitzer MH, Gilbert L, Theodosopoulos PV, Raleigh DR. Epigenetic reprogramming shapes the cellular landscape of schwannoma. Nat Commun. 2024 Jan 12; 15(1):476.  View on PubMed
  6. 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. Spatial genomic, biochemical, and cellular mechanisms drive meningioma heterogeneity and evolution. Res Sq. 2023 May 15.  View on PubMed
  7. 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. MerlinS13 phosphorylation controls meningioma Wnt signaling and magnetic resonance imaging features. Res Sq. 2023 Mar 14.  View on PubMed
  8. 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. Dual genome-wide coding and lncRNA screens in neural induction of induced pluripotent stem cells. Cell Genom. 2022 Nov 09; 2(11).  View on PubMed
  9. 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, Qiu Z, Martin MV, Susko MS, Braunstein SE, Bush NAO, Schulte JD, Butowski N, Sneed PK, Berger MS, Krogan NJ, Perry A, Phillips JJ, Solomon DA, Costello JF, McDermott MW, Rich JN, Raleigh DR. Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities. Nat Genet. 2022 05; 54(5):649-659.  View on PubMed
  10. 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, McDermott MW, Raleigh DR, Braunstein SE. Resection with intraoperative cesium-131 brachytherapy as salvage therapy for recurrent brain tumors. J Neurosurg. 2022 Oct 01; 137(4):924-930.  View on PubMed
  11. Liu SJ, Dang HX, Lim DA, Feng FY, Maher CA. Long noncoding RNAs in cancer metastasis. Nat Rev Cancer. 2021 07; 21(7):446-460.  View on PubMed
  12. 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. miRNA-independent function of long noncoding pri-miRNA loci. Proc Natl Acad Sci U S A. 2021 03 30; 118(13).  View on PubMed
  13. Liu SJ, Horlbeck MA, Weissman JS, Lim DA. Genome-Scale Perturbation of Long Noncoding RNA Expression Using CRISPR Interference. Methods Mol Biol. 2021; 2254:323-338.  View on PubMed
  14. 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, Lim DA. CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma. Genome Biol. 2020 03 31; 21(1):83.  View on PubMed
  15. Horlbeck MA, Liu SJ, Chang HY, Lim DA, Weissman JS. Fitness effects of CRISPR/Cas9-targeting of long noncoding RNA genes. Nat Biotechnol. 2020 May; 38(5):573-576.  View on PubMed
  16. 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, Costello JF, Raleigh DR. Multiplatform Molecular Profiling Reveals Epigenomic Intratumor Heterogeneity in Ependymoma. Cell Rep. 2020 02 04; 30(5):1300-1309.e5.  View on PubMed
  17. 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, Nowakowski TJ, Lim DA, Diaz A, Raleigh DR, Kriegstein AR. Outer Radial Glia-like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma. Cell Stem Cell. 2020 01 02; 26(1):48-63.e6.  View on PubMed
  18. Andersen RE, Hong SJ, Lim JJ, Cui M, Harpur BA, Hwang E, Delgado RN, Ramos AD, Liu SJ, Blencowe BJ, Lim DA. The Long Noncoding RNA Pnky Is a Trans-acting Regulator of Cortical Development In Vivo. Dev Cell. 2019 05 20; 49(4):632-642.e7.  View on PubMed
  19. Liu SJ, Lim DA. Modulating the expression of long non-coding RNAs for functional studies. EMBO Rep. 2018 12; 19(12).  View on PubMed
  20. Kline C, Liu SJ, Duriseti S, Banerjee A, Nicolaides T, Raber S, Gupta N, Haas-Kogan D, Braunstein S, Mueller S. Reirradiation and PD-1 inhibition with nivolumab for the treatment of recurrent diffuse intrinsic pontine glioma: a single-institution experience. J Neurooncol. 2018 Dec; 140(3):629-638.  View on PubMed

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