Keane Lai, M.D.
Assistant Professor, Department of Cancer Biology and Molecular Medicine
Appointments
Assistant Professor, Department of Cancer Biology and Molecular Medicine
Research Teams
In the Keane Lai Lab, we study:
The role of the obscure gene midnolin in the liver. Although midnolin has been studied for over 20 years, its biological roles remain largely unknown. We are the first to demonstrate the functional significance of midnolin in liver cancer: Midnolin expression correlates with poor prognosis in hepatocellular carcinoma (HCC) patients, and suppression of midnolin severely inhibits tumorigenicity of HCC cells in vitro and in an immune-competent orthotopic mouse model. (Kweon et al. Cancers 14(6):1421, 2022.)
The role of Wnt/β-catenin signaling in the liver and pancreas. We are the first to demonstrate that small molecule specific Wnt/CBP/β-catenin antagonist ICG-001 suppresses activation of pancreatic stellate cells (PSCs) as evidenced by their decreased proliferation, down-regulation of activation markers, up-regulation of quiescence marker, and reduced migration of PSCs, as well as by reduced PSC-induced migration of pancreatic cancer cells. (Che et al. Cancers 12(6):1476, 2020.)
Duarte Cancer Center
1500 East Duarte Road
Duarte, CA 91010
Duarte, CA 91010
American Board of Clinical Chemistry
Doctor of Medicine, University of Pittsburgh, Pittsburgh, PA
Bachelor of Science, Biology, magna cum laude, University of California Los Angeles, Los Angeles, CA
Cedars-Sinai Medical Center, Clinical Chemistry, Los Angeles, CA
Research Center for ALPD & Cirrhosis/University of Southern California (Experimental Pathology), Los Angeles, CA
Fred Hutchinson Cancer Ctr/VA (Proteomics), Seattle, WA
University of Washington, Clinical Chemistry, Seattle, WA
University of Washington, Clinical Pathology, Seattle, WA
2022-present, Assistant Professor, Department of Cancer Biology and Molecular Medicine, City of Hope, Duarte, CA
2020-2022, Assistant Professor, Department of Molecular Medicine, City of Hope, Duarte, CA
2017-2020, Associate Clinical Professor, Department of Pathology, City of Hope, Duarte, CA
2011-2017, Assistant Professor of Clinical Pathology, University of Southern California, Los Angeles, CA
Hans Popper Hepatopathology Society
United States Human Proteome Organization
American Society for Investigative Pathology
American Association for the Study of Liver Diseases
American Association for Clinical Chemistry
2022:
Kweon SM, Kim G, Jeong Y, Huang W, Lee JS, Lai KKY*. Midnolin Regulates Liver Cancer Cell Growth In Vitro and In Vivo. Cancers 14(6):1421, 2022. PMID: 35326575. (*Senior corresponding author.)
2021:
Hu X, Ono M, Chimge NO, Chosa K, Nguyen C, Melendez E, Lou CH, Lim P, Termini J, Lai KKY, Fueger PT, Teo JL, Higuchi Y, Kahn M. Differential Kat3 Usage Orchestrates the Integration of Cellular Metabolism with Differentiation. Cancers 13(23):5884, 2021. PMID: 34884992.
Lai KKY, Kahn M. Pharmacologically Targeting the WNT/β-Catenin Signaling Cascade: Avoiding the Sword of Damocles. Handb Exp Pharmacol 269:383-422, 2021. PMID: 34463849.
Tang WC, Chang YW, Che M, Wang MH, Lai KK, Fueger PT, Huang W, Lin SB, Lai KKY*. Thioacetamide-induced norepinephrine production by hepatocytes is associated with hepatic stellate cell activation and liver fibrosis. Curr Mol Pharmacol 2021 Apr 12. doi: 10.2174/1874467214666210412144416. PMID: 33845730. (*Senior corresponding author.)
Lai KKY, Hu X, Chosa K, Nguyen C, Lin DP, Lai KK, Kato N, Higuchi Y, Highlander SK, Melendez E, Eriguchi Y, Fueger PT, Ouellette AJ, Chimge NO, Ono M, Kahn M. p300 Serine 89: A Critical Signaling Integrator and Its Effects on Intestinal Homeostasis and Repair. Cancers 13(6):1288, 2021. PMID: 33799418.
2020:
Che M, Kweon SM, Teo JL, Yuan YC, Melstrom LG, Waldron RT, Lugea A, Urrutia RA, Pandol SJ, Lai KKY*. Targeting the CBP/β-Catenin Interaction to Suppress Activation of Cancer-Promoting Pancreatic Stellate Cells. Cancers 12(6):1476, 2020. PMID: 32516943. (*Senior corresponding author.)
Chong CK, Cheng CYS, Tsoi SYJ, Huang FY, Liu F, Fung J, Seto WK, Lai KK, Lai CL, Yuen MF, Wong DK. HBV X protein mutations affect HBV transcription and association of histone-modifying enzymes with covalently closed circular DNA. Sci Rep. 10(1):802, 2020. PMID: 31964944.
Asahina K, Balog S, Hwang E, Moon E, Wan E, Skrypek K, Chen Y, Fernandez J, Romo J, Yang Q, Lai K, French SW, Tsukamoto H. Moderate alcohol intake promotes pancreatic ductal adenocarcinoma development in mice expressing oncogenic Kras. Am J Physiol Gastrointest Liver Physiol. 318(2):G265-G276, 2020. PMID: 31760766.
2019:
Huang FY, Wong DKH, Tsui VWM, Seto WK, Mak LY, Cheung TT, Lai KKY, Yuen MF. Targeted genomic profiling identifies frequent deleterious mutations in FAT4 and TP53 genes in HBV-associated hepatocellular carcinoma. BMC Cancer 19(1):789, 2019. PMID: 31395065.
Lukaszewicz AI, Nguyen C, Melendez E, Lin DP, Teo JL, Lai KKY, Huttner WB, Shi SH, Kahn M. The Mode of Stem Cell Division Is Dependent on the Differential Interaction of β-Catenin with the Kat3 Coactivators CBP or p300. Cancers 11(7). pii: E962, 2019. PMID: 31324005.
Saloman JL, Albers KM, Cruz-Monserrate Z, Davis BM, Edderkaoui M, Eibl G, Epouhe AY, Gedeon JY, Gorelick FS, Grippo PJ, Groblewski GE, Husain SZ, Lai KKY, Pandol SJ, Uc A, Wen L, Whitcomb DC. Animal Models: Challenges and Opportunities to Determine Optimal Experimental Models of Pancreatitis and Pancreatic Cancer. Pancreas 48(6):759-779, 2019. PMID: 31206467.
Lai KKY*, Nguyen C, Lee KS, Lee A, Lin DP, Teo JL, Kahn M. Convergence of Canonical and Non-Canonical Wnt Signal: Differential Kat3 Coactivator Usage. Curr Mol Pharmacol 12(3):167-183, 2019. PMID: 30836930. (*Co-corresponding author.)
2018:
Ono M*, Lai KKY*, Wu K, Nguyen C, Lin DP, Murali R, Kahn M. Nuclear receptor/Wnt beta-catenin interactions are regulated via differential CBP/p300 coactivator usage. PLoS One 13(7):e0200714, 2018. PMID: 30020971. (*Equal contribution.)
Manegold P*, Lai KKY*, Wu Y, Teo JL, Lenz HJ, Genyk YS, Pandol SJ, Wu K, Lin DP, Chen Y, Nguyen C, Zhao Y, Kahn M. Differentiation Therapy Targeting the β-Catenin/CBP Interaction in Pancreatic Cancer. Cancers 10(4). pii: E95, 2018. PMID: 29596326. (*Equal contribution.)
2017:
Matsushita N, Hassanein MT, Martinez-Clemente M, Lazaro R, French SW, Xie W, Lai K, Karin M, Tsukamoto H. Gender difference in NASH susceptibility: roles of hepatocyte Ikkβ and Sult1e1. PLoS One 12(8):e0181052, 2017. PMID: 28797077.
Lai KKY*, Kweon SM*, Chi F*, Hwang E*, Kabe Y, Higashiyama R, Qin L, Yan R, Wu RP, Lai K, Fujii N, French S, Xu J, Wang JY, Murali R, Mishra L, Lee JS, Ntambi JM, Tsukamoto H. Stearoyl-CoA Desaturase Promotes Liver Fibrosis and Tumor Development in Mice via a Wnt Positive-Signaling Loop by Stabilization of Low-Density Lipoprotein-Receptor-Related Proteins 5 and 6. Gastroenterology 152(6):1477-1491, 2017. PMID: 28143772. (*Equal contribution.)