Ji  Luo, Ph.D.
Ji Luo, Ph.D.
Investigator

Center for Cancer Research
National Cancer Institute

Building 37, Room 4054B
Bethesda, MD 20892
301-451-4725

Our lab focuses on understanding the biology of cancer with mutations in the Ras oncogene. In particular, we are using functional genomics to dissect genetic dependencies and delineate mechanisms of non-oncogene addiction in Ras mutant cells. We are currently investigating the role of SUMO ligases, RNA splicing factors, and certain transcriptional factors support the malignancy of cancer cells with Ras mutation. In addition, we are developing new RNAi and CRISPR tools to identify druggable target combinations in KRAS mutant cells. Lastly, we have developed pharmacological synthetic lethal screens to discovery new therapeutic strategies that can be rapidly translated into clinical trials.

Areas of Expertise
1) Ras oncogene 2) RNAi and CRISPR screen 3) Synthetic lethality 4) Non-oncogene addiction 5) Colorectal cancer 6) Lung Cancer

Our long-term goal is to understand the mechanisms of tumorigenesis and identify new therapeutic strategies for cancer treatment. In particular, we focus on understanding the biology of Ras mutant cancer and identifying new treatment approaches for Ras tumors. Research in the lab focuses on the follow areas:

Synthetic Lethal Partners of the KRAS Oncogene
We have previously conducted RNAi screens to identify synthetic lethal partners of the KRAS oncogene (Luo et al., Cell, 2009). Our current effort is focused on elucidating the molecular mechanisms by which these genes support Ras-driven oncogenesis. In particular, we are studying how RNA splicing factors (Weng et al., PNAS, 2012) and SUMO ligases (Yu et al., submitted) supports the oncogenic activity of KRAS and how these pathways might be exploited for therapeutic gain. Investigation of other candidate synthetic lethal partners of KRAS is also underway. Our analysis indicates that cancer cells exhibit non-oncogene addiction to a broad network of genes that act to alleviate oncogenic stress and enable cancer cell survival. Therapeutic approaches that exploit non-oncogene addiction should provide new avenues to target cancer cells. We are studying bioactive molecules and developing small-molecule inhibitors that target non-oncogene addiction to assess their potentials in cancer therapy.

Genetic Dissection of Cancer Using RNAi and CRISPR
We are developing new RNAi and CRISPR tools to enable genetic screens with improved penetrance and reduced off-target effects. Recently, we have developed new RNAi tools for a combinatorial siRNA screen to identify optimal drug target combinations against KRAS mutant cancer cells (Yuan et al., Cancer Discovery, 2014). We are also developing new vector systems that allow the introduction of complex genetic alternations in cells to better model the genetic complexities seen in human cancer.

Pharmacological Screens
We are investigating new therapeutic modalities against Ras cancers. We have developed a new chemical screening platform for discovering compounds that can destabilize KRAS protein (Carver et al., PLOS One, 2014). As part of the CCR Major Opportunities Initiative, we have developed a pharmacological synthetic lethal screen to identify, from a collection of FDA-approved and clinical-stage compounds, drug combinations that show selective toxicity in KRAS mutant cells. Our goal is to translate these findings into early stage clinical trials within a few years.

Positions: To inquire about potential postdoctoral and postbaccalaureate openings, please e-mail a cover letter and C.V. to Dr. Luo.

Scientific Focus Areas:
Cancer Biology, Cell Biology, Chemical Biology, Genetics and Genomics, Systems Biology
Selected Recent Publications
  1. Yuan TL, Fellmann C, Lee CS, Ritchie CD, Thapar V, Lee LC, Hsu DJ, Grace D, Carver JO, Zuber J, Luo J, McCormick F, Lowe SW
    Cancer Discovery. 4(10): 1182-1197, 2014. [ Journal Article ]
  2. Weng MT, Lee JH, Wei SC, Li Q, Shahamatdar S, Hsu D, Schetter AJ, Swatkoski S, Mannan P, Garfield S, Gucek M, Kim MK, Annunziata CM, Creighton CJ, Emanuele MJ, Harris CC, Sheu JC, Giaccone G, Luo J.
    Proc. Natl. Acad. Sci. U.S.A. 109(52): E3659-67, 2012. [ Journal Article ]
  3. Solimini NL, Xu Q, Mermel CH, Liang AC, Schlabach MR, Luo J, Burrows AE, Anselmo AN, Bredemeyer AL, Li MZ, Beroukhim R, Meyerson M, Elledge SJ.
    Science. 337(6090): 104-109, 2014. [ Journal Article ]
  4. Kessler JD, Kahle KT, Sun T, Meerbrey KL, Schlabach MR, Schmitt EM, Skinner SO, Xu Q, Li MZ, Hartman ZC, Rao M, Yu P, Dominguez-Vidana R, Liang AC, Solimini NL, Bernardi RJ, Yu B, Hsu T, Golding I, Luo J, Osborne CK, Creighton CJ, Hilsenbeck SG, Schiff R, Shaw CA, Elledge SJ, Westbrook TF.
    Science. 335(6066): 348-353, 2011. [ Journal Article ]
  5. Luo J, Emanuele MJ, Li D, Creighton CJ, Schlabach MR, Westbrook TF, Wong KK, Elledge SJ
    Cell. 137(5): 835-848, 2009. [ Journal Article ]

Ji Luo received his B.A. in Natural Sciences from the University of Cambridge, UK in 1998. He completed his Ph.D. training as an HHMI Predoctoral Fellow in the laboratory of Dr. Lewis Cantley at Harvard University, Boston. His Ph.D. research focused on the role of PI 3-kinase in development, diabetes and cancer. Ji Luo undertook his postdoctoral training as an AACR Fellow in the laboratory of Dr. Stephen Elledge at Harvard Medical School, Boston. His postdoctoral research focused on the development of bar-coded shRNA library technologies for genome-wide RNAi synthetic lethal analysis in cancer cells.

Name Position
Chih-Shia Lee Ph.D. Postdoctoral Fellow (Visiting)
Sean Lin Ph.D. Postdoctoral Fellow (Visiting)
Jordan Smith Postbaccalaureate Fellow
Junqiu Yue M.D., Ph.D. Special Volunteer (Visiting)
Garmen Yuen Pre-doctoral Fellow
Haibo Zhang Ph.D. Postdoctoral Fellow (Visiting)

Summary

Our lab focuses on understanding the biology of cancer with mutations in the Ras oncogene. In particular, we are using functional genomics to dissect genetic dependencies and delineate mechanisms of non-oncogene addiction in Ras mutant cells. We are currently investigating the role of SUMO ligases, RNA splicing factors, and certain transcriptional factors support the malignancy of cancer cells with Ras mutation. In addition, we are developing new RNAi and CRISPR tools to identify druggable target combinations in KRAS mutant cells. Lastly, we have developed pharmacological synthetic lethal screens to discovery new therapeutic strategies that can be rapidly translated into clinical trials.

Areas of Expertise
1) Ras oncogene 2) RNAi and CRISPR screen 3) Synthetic lethality 4) Non-oncogene addiction 5) Colorectal cancer 6) Lung Cancer

Research

Our long-term goal is to understand the mechanisms of tumorigenesis and identify new therapeutic strategies for cancer treatment. In particular, we focus on understanding the biology of Ras mutant cancer and identifying new treatment approaches for Ras tumors. Research in the lab focuses on the follow areas:

Synthetic Lethal Partners of the KRAS Oncogene
We have previously conducted RNAi screens to identify synthetic lethal partners of the KRAS oncogene (Luo et al., Cell, 2009). Our current effort is focused on elucidating the molecular mechanisms by which these genes support Ras-driven oncogenesis. In particular, we are studying how RNA splicing factors (Weng et al., PNAS, 2012) and SUMO ligases (Yu et al., submitted) supports the oncogenic activity of KRAS and how these pathways might be exploited for therapeutic gain. Investigation of other candidate synthetic lethal partners of KRAS is also underway. Our analysis indicates that cancer cells exhibit non-oncogene addiction to a broad network of genes that act to alleviate oncogenic stress and enable cancer cell survival. Therapeutic approaches that exploit non-oncogene addiction should provide new avenues to target cancer cells. We are studying bioactive molecules and developing small-molecule inhibitors that target non-oncogene addiction to assess their potentials in cancer therapy.

Genetic Dissection of Cancer Using RNAi and CRISPR
We are developing new RNAi and CRISPR tools to enable genetic screens with improved penetrance and reduced off-target effects. Recently, we have developed new RNAi tools for a combinatorial siRNA screen to identify optimal drug target combinations against KRAS mutant cancer cells (Yuan et al., Cancer Discovery, 2014). We are also developing new vector systems that allow the introduction of complex genetic alternations in cells to better model the genetic complexities seen in human cancer.

Pharmacological Screens
We are investigating new therapeutic modalities against Ras cancers. We have developed a new chemical screening platform for discovering compounds that can destabilize KRAS protein (Carver et al., PLOS One, 2014). As part of the CCR Major Opportunities Initiative, we have developed a pharmacological synthetic lethal screen to identify, from a collection of FDA-approved and clinical-stage compounds, drug combinations that show selective toxicity in KRAS mutant cells. Our goal is to translate these findings into early stage clinical trials within a few years.

Positions: To inquire about potential postdoctoral and postbaccalaureate openings, please e-mail a cover letter and C.V. to Dr. Luo.

Scientific Focus Areas:
Cancer Biology, Cell Biology, Chemical Biology, Genetics and Genomics, Systems Biology

Publications

Selected Recent Publications
  1. Yuan TL, Fellmann C, Lee CS, Ritchie CD, Thapar V, Lee LC, Hsu DJ, Grace D, Carver JO, Zuber J, Luo J, McCormick F, Lowe SW
    Cancer Discovery. 4(10): 1182-1197, 2014. [ Journal Article ]
  2. Weng MT, Lee JH, Wei SC, Li Q, Shahamatdar S, Hsu D, Schetter AJ, Swatkoski S, Mannan P, Garfield S, Gucek M, Kim MK, Annunziata CM, Creighton CJ, Emanuele MJ, Harris CC, Sheu JC, Giaccone G, Luo J.
    Proc. Natl. Acad. Sci. U.S.A. 109(52): E3659-67, 2012. [ Journal Article ]
  3. Solimini NL, Xu Q, Mermel CH, Liang AC, Schlabach MR, Luo J, Burrows AE, Anselmo AN, Bredemeyer AL, Li MZ, Beroukhim R, Meyerson M, Elledge SJ.
    Science. 337(6090): 104-109, 2014. [ Journal Article ]
  4. Kessler JD, Kahle KT, Sun T, Meerbrey KL, Schlabach MR, Schmitt EM, Skinner SO, Xu Q, Li MZ, Hartman ZC, Rao M, Yu P, Dominguez-Vidana R, Liang AC, Solimini NL, Bernardi RJ, Yu B, Hsu T, Golding I, Luo J, Osborne CK, Creighton CJ, Hilsenbeck SG, Schiff R, Shaw CA, Elledge SJ, Westbrook TF.
    Science. 335(6066): 348-353, 2011. [ Journal Article ]
  5. Luo J, Emanuele MJ, Li D, Creighton CJ, Schlabach MR, Westbrook TF, Wong KK, Elledge SJ
    Cell. 137(5): 835-848, 2009. [ Journal Article ]

Biography

Ji Luo received his B.A. in Natural Sciences from the University of Cambridge, UK in 1998. He completed his Ph.D. training as an HHMI Predoctoral Fellow in the laboratory of Dr. Lewis Cantley at Harvard University, Boston. His Ph.D. research focused on the role of PI 3-kinase in development, diabetes and cancer. Ji Luo undertook his postdoctoral training as an AACR Fellow in the laboratory of Dr. Stephen Elledge at Harvard Medical School, Boston. His postdoctoral research focused on the development of bar-coded shRNA library technologies for genome-wide RNAi synthetic lethal analysis in cancer cells.

Team

Name Position
Chih-Shia Lee Ph.D. Postdoctoral Fellow (Visiting)
Sean Lin Ph.D. Postdoctoral Fellow (Visiting)
Jordan Smith Postbaccalaureate Fellow
Junqiu Yue M.D., Ph.D. Special Volunteer (Visiting)
Garmen Yuen Pre-doctoral Fellow
Haibo Zhang Ph.D. Postdoctoral Fellow (Visiting)