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 molecular mechanisms underlying genetic and epigenetic regulation
of 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) epigenetic regulation of PD-L1
and PD-1 in tumor cells and MDSCs; 3) the contrasting functions and underlying mechanisms
of NF-kB in tumor cells and CTLs; 4) functions and underlying mechanisms of cytokines
(IFNs, IL6 and IL10) in CTL effector function and MDSC survival and function; and
4) role of OPN in osteoporosis and immune suppression. Our long-term objective is
to develop molecular mechanism/target-based therapy to enhance the efficacy of immune
checkpoint inhibitor immunotherapy for colorectal and pancreatic cancer.
Selected recent publications:
- 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. Online ahead of print.
- Mohammed L Ibrahim, Chunwan Lu, John D Klement, Priscilla S Redd, Dafeng Yang, Alyssa
D Smith, Kebin Liu. 2020. Expression Profiles and Function of IL6 in Polymorphonuclear Myeloid-Derived
Suppressor Cells. Cancer Immunol Immunother. Online ahead of print.
- 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. doi: 10.1158/0008-5472.CAN-19-2731. Online ahead of print. (invited review).
- Chunwan Lu, John D Klement, Dafeng Yang, Thomas Albers, Iryna O Lebedyeva, Jennifer
L Waller, Kebin Liu. 2020. SUV39H1 Regulates Human Colon Carcinoma Apoptosis and Cell Cycle to Promote
Tumor Growth. Cancer Lett. 476:87-96. PMCID: PMC7138631.
- 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. PMCID: PMC6589175.
- 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. PMCID:PMC6397681.
- 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. PMCID: PMC6264631.
- 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. PMCID:
- Priscilla S. Redd, Chunwan Lu, John D. Klement, Mohammed L. Ibrahim, Gang Zhou, Takumi
Kumai, Esteban Celis & Kebin Liu. 2018. H3K4me3 mediates the NF-κB p50 homodimer binding
to the pdcd1 promoter to activate PD-1 transcription in T cells. OncoImmunology. 7:e1483302. PMCID: PMC6140591.
- Wei Xiao, John D. Klement, Chunwan Lu, Mohammed L Ibrahim, and Kebin Liu. 2018. IFNAR1 controls autocrine type I interferon regulation of PD-L1 expression
in myeloid-derived suppressor cells. Immunol. 2018:264-277. PMCID: PMC6008224.
- 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 Res. 77:2834-2843. PMCID: PMC5495112
- 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. PMCID: PMC5384417
- 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. PMCID: PMC5291187.
- Chunwan Lu, Priscilla S Redd, Jeffrey R Lee, Natasha Savage, and Kebin Liu. 2016. The expression profiles and regulation of PD-L1 in tumor-induced myeloid-derived
suppressor cells. OncoImmunology. 5:e1247135. PMCID: PMC5214087.
Complete List of Publications: