The research program in the Liu Laboratory focuses on the dynamic interactions between
tumor cells and immune cells in the tumor microenvironment. At the molecular level,
we aim at elucidating the mechanisms underlying genetic and epigenetic regulation
of expression of FAS, IRF8, OPN, PD-L1 and PD-1 in tumor cells and/or myeloid-derived
suppressor cells (MDSCs). At the cellular level, we study cytotoxic T lymphocyte (CTL)
activation and the coordination between tumor cells and MDSCs in CTL functional suppression
in the tumor microenvironment. Specifically, our research programs focus on: 1) IRF8
expression regulation and function in MDSCs and tumor cells; 2) Genetic and epigenetic
regulation of expression of FAS, PD-L1 and OPN in tumor cells and MDSCs; 3) Functions
of NF-κB in tumor cells and CTLs; and 4) Role of OPN in osteoporosis and immune suppression.
Our long-term objective is to develop molecular mechanism and target-based therapy
to enhance the efficacy of T cell-based immunotherapy for colorectal and pancreatic
Selected recent publications:
- Chunwan Lu, Zhuoqi Liu, John D Klement, Dafeng Yang, Alyssa D Merting, Dakota Poschel,
Thomas Albers, Jennifer L Waller, Huidong Shi, Kebin Liu. 2021.
WDR5-H3K4me3 epigenetic axis regulates OPN expression to compensate PD-L1 function
to promote pancreatic cancer immune escape. J Immunother Cancer. 9:e002624.
- Huabin Zhu, John D Klement, Chunwan Lu, Priscilla S Redd, Dafeng Yang, Alyssa D Smith,
Dakota B Poschel, Juan Zou, Ding Liu, Peng George Wang, David Ostrov, Nicolas Coant,
Yusuf A Hannun, Aaron H Colby, Mark W Grinstaff, Kebin Liu. 2021. Asah2 Represses the p53-Hmox1 Axis to Protect Myeloid-Derived Suppressor Cells
from Ferroptosis. J Immunol. 206:1395-1404.
- Chunwan Lu, John D Klement, Alyssa D Smith, Dafeng Yang, Jennifer L Waller, Darren
D Browning, David H Munn, Kebin Liu. 2020. p50 suppresses cytotoxic T lymphocyte effector
function to regulate tumor immune escape and response to immunotherapy. J Immunother Cancer. 8:e001365.
- Alyssa D Smith, Chunwan Lu, Daniela Payne, Amy V Paschall, John D Klement, Priscilla
S Redd, Mohammed L Ibrahim, Dafeng Yang, Qimei Han, Zhuoqi Liu, Huidong Shi, Thomas
J Hartney, Asha Nayak-Kapoor, Kebin Liu. 2020. Autocrine IL6-mediated Activation of the STAT3-DNMT Axis Silences the TNFα-RIP1
Necroptosis Pathway to Sustain Survival and Accumulation of Myeloid-Derived Suppressor
Cells. Cancer Res. 80:3145-3156.
- Christopher Gromisch, Motaz Qadan, Mariana Albuquerque Machado, Kebin Liu, Yolonda Colson, Mark W Grinstaff. 2020. Pancreatic Adenocarcinoma: Unconventional
Approaches for an Unconventional Disease. Cancer Res. 80:3179-3192. (Invited review).
- Chunwan Lu, John D. Klement, Wei Xiao, Mohammed Ibrahim, Priscilla S. Redd, Asha Nayak-Kapoor,
Gang Zhou, and Kebin Liu. 2019. Type I IFNs activates STAT3 to regulate effector expression of cytotoxic T
lymphocyte effectors to suppress tumor development. J Immunother Cancer. 7:157.
- Chunwan Lu, Dafeng Yang, John D. Klement, II Kyu Oh, Natasha M. Savage, Jennifer L.
Waller, Aaron H. Colby, Mark W. Grinstaff, Nicholas H. Oberlies, Cedric J. Pearce,
Zhiliang Xie, Samuel K. Kulp, Christopher C. Coss, Mitch A. Phelps, Thomas Albers,
Iryna O. Lebedyeva, and Kebin Liu. 2019. SUV39H1 represses the expression of cytotoxic T lymphocyte effectors to promote
colon tumor immune evasion. Cancer Immunol. Res. 7:414-427.
- John D. Klement, Amy V. Paschall, Priscilla S. Redd, Mohammed L. Ibrahim, Chunwan
Lu, Dafeng Yang, Esteban Celis, Scott I. Abrams, Keiko Ozato, and Kebin Liu. 2018. An Osteopontin/CD44 immune checkpoint controls CD8+ T cell activation and tumor immune evasion. J Clin Invest. 128:5549-5560.
- Mohammed L. Ibrahim, John D. Klement, Chunwan Lu, Priscilla S. Redd, Wei Xiao, Dafeng
Yang, Darren D. Browning, Natasha M. Savage, Phillip J. Buckhaults, Herbert C. Morse
III, and Kebin Liu. 2018. Myeloid-Derived Suppressor Cells Produce IL-10 to Elicit DNMT3b-Dependent
IRF8 Silencing to Promote Colitis-Associated Colon Tumorigenesis. Cell Rep. 25:3036-3046.
- Priscilla S. Redd, Mohammed Ibrahim, Sarah K. Sharman, Amy V. Paschall, Dafeng Yang,
Asha Nayak-Kapoor, and Kebin Liu. 2017. SETD1B activate iNOS expression in myeloid-derived suppressor cells. Cancer
- Chunwan Lu, Asif Talukder, Natasha Savage, Nagendra Singh and Kebin Liu. 2017. Jak-STAT-mediated chronic inflammation impairs cytotoxic T lymphocyte activation
to decrease anti-PD-1 immunotherapy efficacy in pancreatic cancer. OncoImmunology. 6:e1291106.
- Chunwan Lu, Amy V. Paschall, Huidong Shi, Natasha Savage, Jennifer L. Waller, Maria
E. Sabbatini, Nicholas H. Oberlies, Cedric Pearce, Kebin Liu. 2017. The MLL1-H3K4me3 Axis-Mediated Up-Regulation of PD-L1 Contributes to Pancreatic
Cancer Immune Evasion. J Natl Cancer Inst. 109:djw283.
Complete List of Publications