Dr. Raymond Lai is currently appointed as Professor in the Department of Laboratory Medicine & Pathology in the Faculty of Medicine and Dentistry.
Using ALK-positive anaplastic large cell lymphoma (ALK+ALCL) as the primary experimental model, my laboratory has been studying how oncogenic tyrosine kinases such as NPM-ALK mediates and promotes oncogenesis for the past 2 decades. One of the major focuses is related to the interactions between NPM-ALK and the STAT pathway, especially that of STAT1/STAT3. Since 2010, our NPM-ALK research has led us to a highly important embryonic stem cell protein, Sox2. Using a Sox2 transcription activity reporter, we discovered a highly novel intra-tumoral heterogeneity, in which a small subset of stem-like cells can be identified and purified. Most recently, we are studying how these stem-like cells create chemoresistance via directly altering autophagy, a subject that had won the 2016 Nobel Prize in Medicine/Physiology. I am currently recruiting students or post-doctoral fellows to further explore how cancer stem-like cells utilize autophagy to promote cell survival and chemoresistance, and how NPM-ALK/STAT pathway play roles in this context.
autophagy, cancer cell plasticity, Cancer stemness, carcinoma, chemoresistance, Intra-tumoral heterogeneity, lymphoma, Myc, NPM-ALK, Pathology, Sox2, STAT signaling, tyrosine kinase inhibitors
NPM-ALK Is a Key Regulator of the Oncoprotein FOXM1 in ALK-Positive Anaplastic Large Cell Lymphoma. Haque M, Li J, Huang YH, Almowaled M, Barger CJ, Karpf AR, Wang P, Chen W, Turner SD, Lai R. Cancers (Basel). 2019 Aug 6;11(8). pii: E1119. doi: 10.3390/cancers11081119.
Oxidative stress enhances tumorigenicity and stem-like features via the activation of the Wnt/β-catenin/MYC/Sox2 axis in ALK-positive anaplastic large-cell lymphoma. Wu C, Gupta N, Huang YH, Zhang HF, Alshareef A, Chow A, Lai R. BMC Cancer. 2018 Apr 2;18(1):361. doi: 10.1186/s12885-018-4300-2.
High Myc expression and transcription activity underlies intra-tumoral heterogeneity in triple-negative breast cancer. Gupta N, Jung K, Wu C, Alshareef A, Alqahtani H, Damaraju S, Mackey JR, Ghosh S, Sabri S, Abdulkarim BS, Bigras G, Lai R. Oncotarget. 2017 Apr 25;8(17):28101-28115. doi:10.18632/oncotarget.15891.
The use of cellular thermal shift assay (CETSA) to study Crizotinib resistance in ALK-expressing human cancers. Alshareef A, Zhang HF, Huang YH, Wu C, Zhang JD, Wang P, El-Sehemy A, Fares M, Lai R. Sci Rep. 2016 Sep 19;6:33710. doi: 10.1038/srep33710.
A positive feedback loop involving the Wnt/β-catenin/MYC/Sox2 axis defines a highly tumorigenic cell subpopulation in ALK-positive anaplastic large cell lymphoma. Wu C, Zhang HF, Gupta N, Alshareef A, Wang Q, Huang YH, Lewis JT, Douglas DN, Kneteman NM, Lai R. J Hematol Oncol. 2016 Nov 8;9(1):120.
The Opposing Function of STAT3 as an Oncoprotein and Tumor Suppressor is Dictated by the Expression Status of STAT3-beta in Esophageal Squamous Cell Carcinoma. Zhang HF, Chen Y, Wu C, Wu ZY, Tweardy DJ, Alshareef A, Liao LD, Xue YJ, Wu JY, Chen B, Xu XE, Gopal K, Gupta N, Li EM, Xu LY, Lai R. Clin Cancer Res. 2016 Feb 1;22(3):691-703. doi: 10.1158/1078-0432.CCR-15-1253. Epub 2015 Sep 24.
The PI3K/AKT/c-MYC Axis Promotes the Acquisition of Cancer Stem-Like Features in Esophageal Squamous Cell Carcinoma. Zhang HF, Wu C, Alshareef A, Gupta N, Zhao Q, Xu XE, Jiao JW, Li EM, Xu LY, Lai R. Stem Cells. 2016 Aug;34(8):2040-51. doi: 10.1002/stem.2395.
STAT1 is phosphorylated and downregulated by the oncogenic tyrosine kinase NPM-ALK in ALK-positive anaplastic large-cell lymphoma. Wu C, Molavi O, Zhang H, Gupta N, Alshareef A, Bone KM, Gopal K, Wu F, Lewis JT, Douglas DN, Kneteman NM, Lai R. Blood. 2015 Jul 16;126(3):336-45. doi: 10.1182/blood-2014-10-603738.
STAT3 in Cancer-Friend or Foe? Zhang HF, Lai R. Cancers (Basel). 2014 Jul 3;6(3):1408-40. doi: 10.3390/cancers6031408.
Aberrant expression and biological significance of Sox2, an embryonic stem cell transcriptional factor, in ALK-positive anaplastic large cell lymphoma. Gelebart P, Hegazy SA, Wang P, Bone KM, Anand M, Sharon D, Hitt M, Pearson JD, Ingham RJ, Ma Y, Lai R. Blood Cancer J. 2012 Aug 10;2:e82. doi: 10.1038/bcj.2012.27.
Pathobiology of ALK+ anaplastic large-cell lymphoma. Amin HM, Lai R. Blood. 2007 Oct 1;110(7):2259-67. Epub 2007 May 22.