Research
Vision
- Build MCO as a basic/ translational science “hub” at MD Anderson to advance fundamental cancer science that brings innovation to cancer patient care
- Translate new scientific breakthroughs to clinical trials by closely collaborating with clinical colleagues
- Bring cancer science forward globally at new frontiers
Shared Resources
Functional Genomics enables researchers to understand the complicated interactions between genotype and phenotype at a genome-wide scale. ShRNA, Open Reading Frame (ORF) and CRISPR libraries are powerful tools for these types of genetic screens, which have been widely used in the field of cancer research for identifying oncogenes, tumor suppressors, metastasis regulators, drug resistance genes and new therapeutic targets. The Functional Genomics Core aims to promote our basic research and to enhance translational research and drug discovery at the UT MD Anderson Cancer Center.
MCO faculty in Cancer Biology Program
All MCO faculty participate in at least one GSBS graduate program. The followings are examples of MCO faculty’s service to the Cancer Biology Program.
- Dr. Dihua Yu, Executive Committee Member, Cancer Biology Program
- Dr. Paul Chiao, co-director, GSBS Cancer Biology Program
- Dr. Honami Naora: Reappointment for 2nd term on Academic Standards Committee, GSBS; served on GSBS Academic Standard Committee as the representative for the Cancer Biology Program
Education and Training
MCO faculty continues to host a plethora of students from summer programs as well as GSBS tutorial students, gave lectures in GSBS core curriculum.
Faculty
Dr. Liuqing Yang-GSBS Student Scholarship Committee, Committee Member, 9/2020-present
Dr. Min Sup Song- GSBS Curriculum Committee, Member, 10/2019−present
Dr. Haoqiang Ying- GSBS Student Scholarship Committee, member, 9/2019-present & Co-director (with Dr. Jian Hu of Cancer Biology), Basic and Translational Cancer Biology course, GSBS, 1/2020-present
Trainees
MCO trainees are competitive in obtaining prestigious awards in FY20. MCO has two Odyssey Fellows.
Arseniy Yuzhalin, PhD (mentor: Dr. Dihua Yu) is awarded by the Odyssey Program Fellowship (September 1, 2019-August 31, 2022) for his proposed project entitled “Inhibition of CDK5 as a potential therapeutic strategy against breast cancer brain metastasis” & received 2020 Postdoctoral Travel Award from Office of Postdoctoral Affairs & Development (OPAD), MD Anderson Cancer Center, November 2019.
Dr. Ching-Fei Li (mentor: Dr. Paul J Chiao) is awarded by the Odyssey Program Fellowship (September 1, 2020-August 31, 2023) for her proposed project entitled “Investigation of the role of BDKRB1 in PDAC progression and tumor microenvironment”.
Ruth Barros De Paula (mentor: Dr. John A. Tainer) is the winner of the Grad Student elevator speech.
Dr. WonJae Lee (mentor: Dr. Honami Naora)
- Career Development Award, Hera Ovarian Cancer Foundation
- Diane Denson Tobola Fellowship in Ovarian Cancer Research Recognition of Research Excellence.
Select Publications
2021
Hambarde S, Tsia CL, Pandiat RK, Bacolla A, Maitra A, Charaka V, Hunt CR, Kumar R, Limobo L, Le Meur R, Chazin WJ, Tsutakawa S, Russell P, Schlacher K, Panditat TJ*, Tainer JA*. EXO5-DNA structure and BLM interactions direct DNA resection critical for ATR-dependent replication restart, Molecular Cell Jun 24:S1097-2765(21)00420-2, 2021. doi: 10.1016/j.molcel.2021.05.027. *Co-corresponding authors.
Yan L, Tu B, Yao J, Gong J, Carugo A, Bristow CA, Wang Q, Zhu C, Dai B, Kang Y, Han L, Feng N, Jin Y, Fleming J, Heffernan TP, Yao W, Ying H. Targeting glucose metabolism sensitizes pancreatic cancer to MEK inhibition. Cancer Res. Jun 11;canres.3792.2020, 2021. doi: 10.1158/0008-5472.CAN-20-3792. Online ahead of print.
*Yang R†, Sun L†, Li CF, Wang YH, Yao J, Li H, Yan M, Chang WC, Hsu JM, Cha JH, Hsu JL, Chou CW, Sun X, Deng Y, Chou CK, Yu D, *Hung MC. Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy †Equal contribution *co-corresponding authors. Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy †Equal contribution *co-corresponding authors. Nature Comm Feb 5; 12:832, 2021. PMC7864927. https://doi.org/10.1038/s41467-021-21099-2
Hammel M, Rashid I, Sverzhinsky A, Pourfarjam Y, Tsai MS, Ellenberger T, Pascal JM, *Kim IK, *Tainer JA, *Tomkinson AE. An atypical BRCT–BRCT interaction with the XRCC1 scaffold protein compacts human DNA Ligase IIIα within a flexible DNA repair complex. Nucleic Acids Res. Jan 11;49(1):306-321, 2021 (Dec 16, 2020 online ahead of print). PMC7797052. doi:10.1093/nar/gkaa1188. **Co-corresponding authors
2020
Houl JH, Ye Z, Brosey CA, Balapiti-Modarage LPF, Namjoshi S, Bacolla A, Laverty D, Walker BL, Pourfarjam Y, Warden LS, Babu Chinnam N, Moiani D, Stegeman RA, Chen MK, Hung MC, Nagel ZD, Ellenberger T, Kim IK, Jones DE, Ahmed Z, Tainer JA. Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death. Nature Communications Dec 11;10(1):5654, 2019. *T32 trainee. PMC6906431. doi: 10.1038/s41467-019-13508-4
Tsai CL, Tripp P, Sivabalasarma S, Zhang C, Rodriguez-Franco M, Wipfler RL, Chaudhury P, Banerjee A, Beeby M, Whitaker RJ, #Tainer JA, #Albers SV. The periplasmic FlaG/F complex structure and its essential role for archaellar swimming motility. Nature Microbiology Jan;5(1):216-225. 2020. #Co-corresponding authors. PMC6952060. doi: 10.1038/s41564-019-0622-3
#Alam H, #Tang M, Maitituoheti M, Dhar SS, Kumar M, Han CY, Ambati CR, Amin SB, Gu B, Chen TY, Lin YH, Chen J, Muller FL, Putluri N, Flores
ER, DeMayo FJ, Baseler L, *Rai K, *Lee MG . KMT2D deficiency impairs super-enhancers to confer a glycolytic vulnerability in lung cancer. Cancer
Cell April 13; 37:599‒617 (Epub Apr 2) e7, 2020. #equal contribution. *co-corresponding authors. PMC7178078. doi: 10.1016/j.ccell.2020.03.005
#*Xu D, #Wang Z, Xia Y, Shao F, Xia W, Wei Y, Li X, Qian X, Lee JH, Du L, Zheng Y, Lv G, Leu JS, Wang H, Xing D, Liang T, *Hung MC, *Lu Z.
The gluconeogenic enzyme PCK1phosphorylates INSIG1/2 for lipogenesis. Nature Apr;580(7804):530-535, 2020. #equal contribution and *co-corresponding authors. Dr. Daqian Xu was an Odyssey Fellow in MCO and has been recruited as a tenure-track faculty by another institution. PMID:
32322062.doi:10.1038/s41586-020-2183-2
Zhang L, Yao J, Wei Y, Zou ZF, Li P, Qu JK, Badu-Nkansah A, Yuan XL, Huang YW, Fukumura K, Mao X, Chang WC, Saunus J, Lakhani S, Huse J,
Hung MC, Yu D. Blocking immunosuppressive neutrophils deters pY696-EZH2-driven brain metastases. Science Translational Medicine May 27;
12(545):eaaz5387, 2020. PMID32461334. doi:10.1126/scitranslmed.aaz5387
Tsutakawa SE, Sarker AH, Ng C, Arvai AS, Shin DS, Shih B, Jiang S, Thwin AC, Tsai MS, Willcox A, Her MZ, Trego KS, Raetz AG, Rosenberg D,
Bacolla A, Hammel M, Griffith JD, Cooper PK, Tainer JA. Human XPG nuclease structure, assembly and activities with insights for neurodegeneration and cancer from pathogenic mutations. Proc Natl Acad Sci U S A. 2020 Jun 23;117(25)14127-14138, 2020. PMC7321962. doi:10.1073/pnas.1921311117
Hou J, Zhao R, Xia W, Chang CW, You Y, Hsu JM, Nie L, Chen Y, Wang YC, Liu C, Wang WJ, Wu Y, Ke B, Hsu JH, Huang K, Ye Z, Yang Y, Xia X,
Li Y, Li CW, Shao B, Tainer JA, Hung MC. PD-L1-mediated Gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumor necrosis. Nature Cell Biology, Oct;22(10):1264-1275 (Sept 14 Epub online) 2020. doi: 10.1038/s41556-020-0575-z. PMC7653546
Liu CX†, Zha Z†, Zhou C†, Chen Y, Xia W, Wang YN, Lee HH, Yin Y, Yan M. Chang CW, Qiu Y, Li H, Li CW, Hsu JM, Hsu JL, Wang SC, Ren
N*, Hung MC*. Ribonuclease 7-driven activation of ROS1 is a new potential therapeutic target in hepatocellular carcinoma. J of Hepatology Apr;74(4):907-918, (Oct 5, Epub online, 2020), 2021. PMCID:7979498. † Equal contribution; *Co-corresponding authors
Thapar R, Wang JL, Hammel M, Ye R, Liang, K, Sun C, Hnizda A, Liang S, Maw SS, Lee L, Villarreal H, Forrester I, Fang S, Tsai MS, Blundell TL, Davis AJ, Lin C, Lees-Miller S, Strick TR, and Tainer, JA. Mechanism of efficient double-strand break repair by a long non-coding RNA. Nucleic Acids Res, Nov
4;48(19):10953-10972 (Oct 12 Epub online), 2020. PMC7641761, doi: 10.1093/nar/gkaa784
Zhang Y†, Li Y†, Hu Q, Xing Z, Zhang Z, Hung L, Wu J, Liang K, Nguyen TK, Egranov SD, Sun C, Zhao Z, Hawke DH, Li J, Sun D, Kim JJ, Zhang
P, Cheng J, Farida A, Hung MC, Han L, Darabi R, Lin C*, Yang L*. LncRNA H19 alleviates muscular dystrophy through stabilizing dystrophin. Nature Cell Biology Nov;22(11):1332-1345, 2020. PMID33106653. doi:10.1038/s41556-020-00595-5 (Oct 26 Epub online), 2020. *Co-corresponding authors. † Equal contribution.
Bacolla A, Sengupta S, Ye Z, Yang C, Mitra J, De-Paula RB, Hegde ML, Ahmed Z, Mort M, Cooper DN, Mitra S, Tainer JA. Heritable pattern of oxidized DNA base repair coincides with pre-targeting of repair complexes to open chromatin. Nucleic Acids Res. Jan 11;49(1):221-243, 2021(Dec 9, 2020 online ahead of print). PMC7797072. doi: 10.1093/nar/gkaa1120
2019
Hammel M, Rashid I, Sverzhinsky A, Pourfarjam Y, Tsai MS, Ellenberger T, Pascal JM, *Kim IK, *Tainer JA, *Tomkinson AE. An atypical BRCT–BRCT interaction with the XRCC1 scaffold protein compacts human DNA Ligase IIIα within a flexible DNA repair complex. Nucleic Acids Res. Jan 11;49(1):306-321, 2021 (Dec 16, 2020 online ahead of print). PMC7797052. doi:10.1093/nar/gkaa1188. **Co-corresponding authors
Ko SY, Lee W, Kenny HA, Dang LH, Ellis LM, Jonasch EW, Lengyel E & Naora H. Cancer-derived small extracellular vesicles promote angiogenesis by heparin-bound, bevacizumab-insensitive VEGF, independent of vesicle uptake. Comm Biol Oct 18;2, 386, 2019. (a Nature new journal, and estimated impact factor 10-12). PMC6802217. doi:10.1038/s42003-019-0609-x
Hu Q, Ye Y, Chan LC, Li Y, Liang K, Lin A, Egranov SD, Zhang Y, Xia W, Gong J, Pan Y, Chattterjee SS, Yao J, Evans KW, Nguyen TK, Park PK, Liu J, Coarfa C, Donepudi SR, Putluri V, Putluri N, Hawke DH, Marks JR, Gunaratne PH, Caudle AS, Sahin AA, Hortobagyi GN, Meric-Bernstam M, Chen L, Yu D, Hung MC, Curran MA, Han L, Lin C, Yang L. Oncogenic LncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression. Nature Immunology 20(7):835-851, 2019.
Park MK, Yao Y, Xia W, Setijono SR, Kim JH, Vila I, Chiu HH, Wu Y, Billalabeitia E, Lee MG, Kalb RG, Hung MC, Pandolfi PP, Song SJ, Song MS. PTEN self-regulates through USP11 via the PI3K-FOXO pathway to stabilize tumor suppression. Nature Communications 10(1):636, 2019.
Li Y, Hu Q, Li C, Liang K, Xiang Y, Hsiao H, Nguyen TK, Park PK, Egranov SD, Ambati CR, Putluri N, Hawke DH, Han L, Hung MC, Danesh FR, Yang L, Lin C, PTEN-induced Partial epithelial-mesenchymal transition drives diabetic kidney Disease. J. Clinic. Invest. 129(3):1129-1151, 2019
Li H, Li CW, Li X, Ding Q, Guo L, Liu C, Lai CC, Hsu JM, Dong Q, Xia W, Hsu JL, Yamaguchi H, Du Y, Lai YJ, Koller PB, Ye Q, Hung MC. c-MET inhibitors induce immune resistance through PD-L1 stabilization in hepatocellular carcinoma. Gastroenterology 156(6):1849-1861, 2019.
Hu Q, Li , Wang SY, Li Y, Wen B, Zhang YY, Liang K, Yao J, Ye YQ, Hsiao H, Nguyen TK, Park PK, Egranov SD, Hawke DH, Marks JR, Han L, Hung MC, Zhang B, Lin C, Yang L. LncRNAs-directed PTEN enzymatic switch governs epithelial-mesenchymal transition. Cell Res 29(4):286-304, 2019.
Yang Y, Hsu JM, Sun L, Li CW, Chan LC, Wei Y, Xia W, Hou J, Hsu JL, Hung MC. Palmitoylation stabilizes PD-L1 to promote breast tumor growth. Cell Res 29(1):83-86, 2019.
Lee W, Ko SY, Mohamed MS, Kenny HA, Lengyel E, Naora H. Neutrophils facilitate ovarian cancer pre-metastatic niche formation in the omentum. J Exp Med 7;216(1):176-194, 2019.
Liu Y, Qin S, Chen T-Y, Lei M, Dhar SS, Ho JC, Dong A, Loppnau P, Li Y, Lee MG‡, & Min J‡ A novel binding mode of histone H4 by MLL3/4 provides insights into a trans-histone regulatory mechanism of H3K4 methylation ‡Co-corresponding author. Nature Communications 3;10(1):36, 2019.
Wilkinson AE, Diep J, Dai S, Liu S, Ooi YS, Song D, Li TM, Horton JR, Zhang X, Liu C, Trivedi DV, Ruppel KM, Vilches-Moure JG, Casey KM, Mak J, Cowan T, Elias JE, Nagamine CM, Spudich JA, Cheng X*, Carette JE*, Gozani O*. SETD3 is an actin histidine methyltransferase that prevents primary dystocia. *Co-corresponding authors. Nature 565(7739):372-376, 2019.
Yang Y, Hsu JM, Sun L, Chan LC, Li CW, Hsu JL, Wei Y, Xia W, Hou J, Qiu Y, Hung MC. Palmitoylation stabilizes PD-L1 to promote breast tumor growth. Cell Res 29(1):83-86, 2019.
Lee HH, Wang YN, Xia W, Chen CH, Rau KM, Ye L, Wei Y, Chou CK, Wang SC, Yan M, Tu CY, Hsia TC, Chiang SF, Chao KSC, Wistuba II, Hsu JL, Hortobagyi GN, Hung MC. Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy. Cancer Cell 2019 Aug 12;36(2):168-178.e4..
2018
Lee PC, Fang YF, Yamaguchi H, Wang WJ, Chen TC, Hong X, Ke B, Xia X, Wei Y, Zha Z, Wang Y, Kuo HP, Wang CW, Tu CY, Chen CH, Huang WC, Chiang SF, Nie L, Hou J, Chen CT, Huo L, Yang WH, Deng R, Nakai K, Hsu YH, Chang SS, Chiu TJ, Tang J, Chang SJ, Zhang R, Wang L, Fang B, Chen T, Wong KK, Hsu JL, Hung MC. Targeting PKCδ as a therapeutic strategy against the heterogeneity of EGFR inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell 34(6):954-969, 2018.
Cha JH, Yang WH, Xia W, Wei Y, Chan LC, Lim SO, Li CW, Kim T, Chang SS, Lee HH, Hsu JL, Wang HL, Kuo CW, Chang WC, Hadad S, Purdie CA, McCoy AM, Cai S, Tu Y, Litton JK, Mittendorf EA, Moulder SL, Symmans WF, Thompson AM, Piwnica-Worms H, Chen CH, Khoo KH, Hung MC. Metformin promotes antitumor immunity via endoplasmic reticulum-associated degradation of PD-L1. Molecular Cell 16;71(4):606-620, 2018.
Yang Y, Li CW, Chan LC, Wei Y, Hsu J, Xia W, Chan JH, Hou J, Hsu JL, Sun L, Hung MC. Exosomal PD-L1 harbors active defense function to suppress T cell killing and promote tumor growth of breast cancer cells. Cell Res 28(8):862-864, 2018.
Dhar SS, Zhao D, Lin T, Gu B, Pal K, Wu SJ, Alam H, Lv J, Yun K, Gopalakrishnan V, Flores ER, Northcott PA, Rajaram V, Li W, Shilatifard A, Sillitoe RV, *Chen K, *Lee MG. MLL4 Is required to maintain broad H3K4me3 peaks and super-enhancers at tumor suppressor genes. Molecular Cell 70(5):825-841, 2018. *Co-corresponding authors.
Wang D, Horton JR, Zheng Y, Blumenthal RM, Zhang X, Cheng X. Role for first zinc finger of WT1 in DNA sequence specificity: Denys-Drash syndrome-associated WT1 mutant in ZF1 enhances affinity for a subset of WT1 binding sites. Nucleic Acids Res 46(8):3864-3877, 2018.
Wang YN, Lee HH, Chou CK, Yang WH, Wei Y, Chen CT, Yao J, Hsu JL, Zhu C, Ying H, Ye Y, Wang WJ, Lim SO, Xia W, Ko HW, Liu X, Liu CG, Wu X, Wang H, Li D, Prakash LR, Katz MH, Kang Y, Kim M, Fleming JB, Fogelman D, Javle M, Maitra A, Hung MC. Angiogenin/ribonuclease 5 is an EGFR ligand and a serum biomarker for erlotinib sensitivity in pancreatic cancer. Cancer Cell 33(4): 752-769, 2018.
Patel A, Yang P, Tinkham M, Pradhan M, Sun MA, Wang Y, Hoang D, Wolf G, Horon JR, Zhang X, Macfarlan T, Cheng X. DNA Conformation Induces Adaptable Binding by Tandem Zinc Finger Proteins. Cell 173:1-13, 2018
Guo HF, Tsai CL, Terajima M, Tan X, Banerjee P, Miller MD, Liu X, Yu J, Byemerwa J, Alvarado S, Kaoud TS, Dalby KN, Bota-Rabassedas N, Chen Y, Yamauchi M, *Tainer JA, *Phillips GN Jr, *Kurie JM. Pro-metastatic collagen lysyl hydroxylase dimer assemblies stabilized by Fe2+-binding. Nature Communications 9(1):512, 2018. *Co-corresponding authors.
Wan L, Xu K, Wei Y, Zhang J, Han T, Fry C, Zhang Z, Wang YV, Huang L, Yuan M, Xia W, Chang WC, Huang WC, Liu CL, Chang YC, Liu J, Wu Y, Jin VX, Dai X, Guo J, Liu J, Jiang S, Li J, Asara JM, Brown M, Hung MC*, Wei W*. Phosphorylation of EZH2 by AMPK suppresses PRC methyltransferase activity and oncogenic function. Molecular Cell 69(2):279-291, 2018. *Co-corresponding authors.
Li CW, Lim SO, Chung EM, Kim YS, Park AH, Yao J, Cha JH, Xia W, Chan LC, Kim T, Chang SS, Lee HH, Chou CK, Liu YL, Yeh HC, Perillo EP, Dunn AK, Kuo CW, Khoo KH, Hsu JL, Wu Y, Hsu JM, Yamaguchi H, Huang TH, Sahin AA, Hortobagyi GN, Yoo SS, Hung MC. Eradication of triple-negative breast cancer cells by targeting glycosylated PD-L1. Cancer Cell 33(2):187-201, 2018.
Hsu JM, Xia W, Hsu YH, Chan LC, Yu WH, Cha JH, Chen CT, Liao HW, Kuo CW, Khoo KH, Hsu JL, Li CW, Lim SO, Chang SS, Chen YC, Ren GX, Hung MC. STT3-dependent PD-L1. STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion. Nature Communications 9(1):1908, 2018.