Jeongwu Lee Laboratory

Research

Our laboratory studies the biology of glioblastoma (GBM), the most aggressive subtype of brain tumors. Using a combination of cell biology, genomics and molecular biology, we aim to identify factors and pathways that are critical for cancer progression and treatment resistance with an ultimate goal of developing effective therapeutic strategies. Our lab’s recent focus is to understand the biology of senescence during glioblastoma progression and treatment resistance, including the immunophenotype and cellular characterization of senescent cells, and the development of novel senolytic agents. This project will likely provide a launching point for new research directions in various aging-associated pathologies.

Selected Publications

Yin J, Kim SS, Choi E, Oh YT, Lin W, Kim TH, Sa JK, Hong JH, Park SH, Kwon HJ, Jin X, You Y, Kim JH, Kim H, Son J, Lee J, Nam DH, Choi KS, Shi B, Gwak HS, Yoo H, Iavarone A, Kim JH, Park JB. ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages. Nat Commun. 2020 Jun 12;11(1):2978.

Sa JK, Chang N, Lee HW, Cho HJ, Ceccarelli M, Cerulo L, Yin J, Kim SS, Caruso FP, Lee M, Kim D, Oh YT, Lee Y, Her NG, Min B, Kim HJ, Jeong DE, Kim HM, Kim H, Chung S, Woo HG, Lee J, Kong DS, Seol HJ, Lee JI, Kim J, Park WY, Wang Q, Sulman EP, Heimberger AB, Lim M, Park JB, Iavarone A, Verhaak RGW, Nam DH. Transcriptional regulatory networks of tumor-associated macrophages that drive malignancy in mesenchymal glioblastoma. Genome Biol. 2020 Aug 26;21(1):216.

 Shin YJ, Sa JK, Lee Y, Kim D, Chang N, Cho HJ, Son M, Oh MYT, Shin K, Lee JK, Park J, Jo YK, Kim M, Paddison PJ, Tergaonkar V, Lee J*, Nam DH*. PIP4K2A as a negative regulator of PI3K in PTEN-deficient glioblastoma. J Exp Med. 2019; 216(5):1120-1134. *corresponding authors.

 Lee JK, Liu Z, Sa JK, Shin S, Wang J, Bordyuh M, Cho HJ, Elliott O, Chu T, Choi SW, Rosenbloom DIS, Lee IH, Shin YJ, Kang HJ, Kim D, Kim SY, Sim MH, Kim J, Lee T, Seo YJ, Shin H, Lee M, Kim SH, Kwon YJ, Oh JW, Song M, Kim M, Kong DS, Choi JW, Seol HJ, Lee JI, Kim ST, Park JO, Kim KM, Song SY, Lee JW, Kim HC, Lee JE, Choi MG, Seo SW, Shim YM, Zo JI, Jeong BC, Yoon Y, Ryu GH, Kim NKD, Bae JS, Park WY, Lee J, Verhaak RGW, Iavarone A, Lee J, Rabadan R, Nam DH. Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy. Nature Genetics 2018 Oct;50(10):1399-1411.

 Jeon HM, Lee J. MET: roles in epithelial-mesenchymal transition and cancer stemness. Ann Transl Med. 2017 Jan;5(1):5. doi: 10.21037/atm.2016.12.67.

 Lee JK, Chang N, Yang H, Cho H, Kim E, Shin YJ, Kang W, Oh YT, Mun GI, Joo KM, Yoon Y, Nam DH, Lee J. USP1 Targeting Impedes GBM Growth by Inhibiting Stem Cell Maintenance and Radioresistance. Neuro Oncology 2016, 18, 37-47

 Lee JK, Nam DH, Lee J. Repurposing antipsychotics as glioblastoma therapeutics: Potentials and challenges. Oncol Lett. 2016 Feb;11(2):1281-1286. doi: 10.3892/ol.2016.4074.

 Kim E, Kim M, Woo DH, Shin Y, Shin J, Chang N, Oh YT, Kim H, Rheey J, Nakano N, Lee C, Joo KM, Rich JN, Nam DH, Lee J. Phosphorylation of the Polycomb component EZH2 by AKT activates STAT3 and promotes self-renewal and tumorigenicity of glioblastoma stem-like cells. Cancer Cell, 2013, 23, 839-852. (Featured in Cancer Cell and selected as the best Cancer Cell collection in 2013)

Kim J, Cho HJ, Park CK, Lee IH, Nam S, Kim Y, Kim BS, Johnson MD, Kong DS, Seol SJ, Lee JI, Joo KM, Yoon Y, Park WY, Lee J, Park JP, Nam DH. Spatio-temporal evolution of the primary glioblastoma genome.  Cancer Cell, 2015, 28, 318-328.

Toledo CM, Ding Y, Hoellerbauer P, Davis RJ, Basom R, Girard EJ, Lee E, Corrin P, Hart T, Bolouri H, Davison J, Zhang Q, Hardcastle J, Aronow BJ, Plaisier CL, Baliga NS, Moffat J, Lin Q, Li XN, Nam DH, Lee J, Pollard SM, Zhu J, Delrow JJ, Clurman BE, Olson JM, Paddison PJ. Genome-wide CRISPR-Cas9 Screens Reveal Loss of Redundancy between PKMYT1 and WEE1 in Glioblastoma Stem-like Cells. Cell Reports, 2015;13(11):2425-39.

 Yin J, Park G, Kim TH, Hong JH, Kim YJ, Jin X, Kang S, Jung JE, Kim JY, Yun H, Lee JE, Kim M, Chung J, Kim H, Nakano I, Gwak HS, Yoo H, Yoo BC, Kim JH, Hur EM, Lee J, Lee SH, Park MJ, Park JB. Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells.  PLoS Biol. 2015 May 20;13(5):e1002152

Sa J, Yoon Y, Kim M, Kim Y, Cho HJ, Lee JK, Shin YJ, Joo KM, Paddison PJ, Ishitani T, Lee J*, Nam DH*. In Vivo RNAi screen identifies NLK as a negative regulator of mesenchymal activity in glioblastoma. Oncotarget, 2015, 6(24):20145-59. * Co-corresponding authors

Chudnovsky Y, Kim D, Zheng S, Whyte WA, Bansal M, Bray MA, Gopal S, Theisen MA, Bilodeau S, Thiru P, Muffat J, Yilmaz OH, Mitalipova M, Woolard K, Lee J, Nishimura R, Sakata N, Fine HA, Carpenter AE, Silver SJ, Verhaak RG, Califano A, Young RA, Ligon KL, Mellinghoff IK, Root DE, Sabatini DM, Hahn WC, Chheda MG. ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state. Cell Reports, 2014;6(2):313-24.

 Hubert CG, Bradley RK, Ding Y, Toledo CM, Herman J, Skutt-Kakaria K, Girard EJ, Davison J, Berndt J, Corrin P, Hardcastle J, Basom R, Delrow JJ, Webb T, Pollard SM, Lee J, Olson JM, Paddison PJ. Genomewide RNAi screens in human brain tumor isolates reveal a novel viability requirement for PHF5A. Genes & Dev, 2013, 27, 1032-1045.

Joo KM, Kim J, Jin J, Kim M, Seol HJ, Muradov J, Yang H, Choi YL, Park WY, Kong DS, Lee JI, Ko YH,Woo HG, Lee J, Kim S, Nam DH, Patient specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastoma in situ. Cell Reports, 2013, 3(1): 260-273.

Ding Y, Hubert CG, Herman J, Corrin P, Toledo CM, Skutt-Kakaria K, Vazquez J, Basom R, Zhang B, Risler JK, Pollard SM, Nam DH, Delrow JJ, Zhu J, Lee J, Deluca J, Olson JM, Paddison PJ. Cancer-specific requirement for BUB1B/BubR1 in human brain tumor isolates and genetically transformed cells. Cancer Discovery 2013, 3, 198-211.

 Joo KM, Jin J, Kim E, Kim KH, Kim BG, Kang YJ, Kang BG, Lathia JD, Cheng KH, Song P, Kim H, Seol HJ, Kong DS, Lee JI, Rich JN, Lee J*, Nam DH*. MET Signaling Regulates Glioblastoma Stem Cells. Cancer Research, 2012 * Co-corresponding authors 

Son MJ, Woolard K, Nam DH, Lee J*, Fine HA*. SSEA-1 is an enrichment marker for tumor initiating cells in human glioblastoma. Cell Stem Cell, 2009;4:440-452. * Co-corresponding authors

Lee J, Son MJ, Woolard K, Donin NM, Li A, Cheng CH, Kotliarova S, Kotliarov Y, Walling J, Ahn S, Kim MS, Totonchy M, Cusack T, Ene C, Ma H, Su Q, Zenklusen JC, Zhang W, Maric D, and Fine HA. Epigenetic-mediated dysfunction of the Bone morphogenetic protein pathway inhibits differentiation of human glioblastoma initiating cells. Cancer Cell, 2008; 13: 69-80. (Featured in Nature and Nature Reviews Cancer)

Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin NM, Pastorino S, Benjamin W. Purow BW, Christopher N, Zhang W, Park JK, Fine HA. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell, 2006; 9:391-403. (Featured in Nature Reviews Cancer, NCI update, and US News and World Report: Cited 1800 times according to Scopus).