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Eric  Le-Lau

Eric Le-Lau, PhD

Program: Tumor Microenvironment and Metastasis

Research Program: Molecular Medicine Program

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  • Overview

    Dr. Lau's research program focuses on elucidating (i) how protein fucosylation regulates tumor intrinsic biology and tumor:stromal interactions, and (ii) how the dietary sugar L-fucose and fucosylated proteins can be leveraged as novel therapeutic and diagnostic approaches to treat cancer.

    Associations

    • Tumor Microenvironment and Metastasis
    • Cutaneous Oncology
    • Molecular Medicine Program
    • Melanoma & Skin Cancer Center of Excellence

    Education & Training

    Graduate:

    • University of California, San Diego, PhD - Molecular Pathology

    Fellowship:

    • Sanford-Burnham Medical Research Institute - Research Fellowship
  • Research Interest

    Dr. Eric Lau earned his B.S. in Molecular Biology at the University of California, San Diego (UCSD) and his Ph.D. in Molecular Pathology at UCSD & the Sanford Burnham Prebys Medical Discovery Institute (SBPMDI) in La Jolla. Following his doctoral studies, which focused on aberrant DNA replication checkpoint signaling in cancer, Eric stayed on at SBPMDI to do his postdoctoral training in the laboratory of Dr. Ze’ev Ronai, where he studied the oncogenic vs. tumor-suppressive roles of the ATF2 transcription factor in melanoma. At the end of his postdoctoral studies, he discovered that protein fucosylation, a process that is regulated by ATF2, can drive melanoma pathogenesis. How fucosylation regulates tumor intrinsic and tumor:stromal interactions—using both melanoma and breast cancer as models—would ultimately became the focus of his laboratory that he established after joining the faculty at Moffitt Cancer Center in 2015. Currently, Eric’s laboratory team focuses on uncovering and delineating key mechanistic roles that fucosylation plays in controlling tumor cell-intrinsic signal transduction and tumor interactions with stromal cells (e.g., tumor-infiltrating immune cells and fibroblasts) that determine immune evasive and metastatic capacities of tumors. In addition, the team also focuses on elucidating novel pathogenic contributions of sex hormones in tumors that are not classically considered as sex-associated (e.g., testosterone-stimulated fucosylation that drives melanoma invasiveness). Ultimately, Eric's team aims to determine how dietary L-fucose and specific fucosylated proteins can be leveraged as novel therapeutic treatments, targets, and diagnostic/prognostic biomarkers for cancer. In addition, Eric is also co-creator of Moffitt's Patient Researcher Forum (https://youtu.be/wvt-BXYw6u4 and https://moffitt.org/patient-family/patient-and-family-centered-care/patient-researcher-forum/), a program that has piqued the interest of healthcare centers across the nation, internationally, and even the interest of First Lady, Dr. Jill Biden (https://youtu.be/JK1ki68OtqI). Eric and his team prioritize patient outreach/education and patient-centered research—and together with the Patient and Family Advisory Council and the Office of Community Outreach, Engagement & Equity—are making strides to further engage and integrate patients and their families into the research enterprise. 

  • Publications

    • Liu Q, Adhikari E, Lester DK, Fang B, Johnson JO, Tian Y, Mockabee-Macias AT, Izumi V, Guzman KM, White MG, Koomen JM, Wargo JA, Messina JL, Qi J, Lau EK. Androgen drives melanoma invasiveness and metastatic spread by inducing tumorigenic fucosylation. Nat Commun. 2024 Feb.15(1):1148. Pubmedid: 38326303. Pmcid: PMC10850104.
    • Lau EK. Research does not happen in a socio-political vacuum - we should not pretend that it does. Nat Rev Cancer. 2023 Nov.23(11):725-726. Pubmedid: 37723271.
    • Ilter D, Drapela S, Schild T, Ward NP, Adhikari E, Low V, Asara J, Oskarsson T, Lau EK, DeNicola GM, McReynolds MR, Gomes AP. NADK-mediated de novo NADP(H) synthesis is a metabolic adaptation essential for breast cancer metastasis. Redox Biol. 2023 May.61:102627. Pubmedid: 36841051. Pmcid: PMC9982641.
    • Vellano CP, White MG, Andrews MC, Chelvanambi M, Witt RG, Daniele JR, Titus M, McQuade JL, Conforti F, Burton EM, Lastrapes MJ, Ologun G, Cogdill AP, Morad G, Prieto P, Lazar AJ, Chu Y, Han G, Khan MAW, Helmink B, Davies MA, Amaria RN, Kovacs JJ, Woodman SE, Patel S, Hwu P, Peoples M, Lee JE, Cooper ZA, Zhu H, Gao G, Banerjee H, Lau M, Gershenwald JE, Lucci A, Keung EZ, Ross MI, Pala L, Pagan E, Segura RL, Liu Q, Borthwick MS, Lau E, Yates MS, Westin SN, Wani K, Tetzlaff MT, Haydu LE, Mahendra M, Ma X, Logothetis C, Kulstad Z, Johnson S, Hudgens CW, Feng N, Federico L, Long GV, Futreal PA, Arur S, Tawbi HA, Moran AE, Wang L, Heffernan TP, Marszalek JR, Wargo JA. Author Correction: Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy. Nature. 2023 Jan.613(7945):E3. Pubmedid: 36627494.
    • Lester DK, Burton C, Gardner A, Innamarato P, Kodumudi K, Liu Q, Adhikari E, Ming Q, Williamson DB, Frederick DT, Sharova T, White MG, Markowitz J, Cao B, Nguyen J, Johnson J, Beatty M, Mockabee-Macias A, Mercurio M, Watson G, Chen PL, McCarthy S, MoranSegura C, Messina J, Thomas KL, Darville L, Izumi V, Koomen JM, Pilon-Thomas SA, Ruffell B, Luca VC, Haltiwanger RS, Wang X, Wargo JA, Boland GM, Lau EK. Fucosylation of HLA-DRB1 regulates CD4+ T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy. Nat Cancer. 2023 Feb.4(2):222-239. Pubmedid: 36690875. Pmcid: PMC9970875.
    • Medina E, Easa Y, Lester DK, Lau EK, Sprinzak D, Luca VC. Structure of the planar cell polarity cadherins Fat4 and Dachsous1. Nat Commun. 2023 Feb.14(1):891. Pubmedid: 36797229. Pmcid: PMC9935876.
    • Adhikari E, Liu Q, Johnson J, Stewart P, Marusyk V, Fang B, Izumi V, Bowers K, Guzman KM, Koomen JM, Marusyk A, Lau EK. Brain metastasis-associated fibroblasts secrete fucosylated PVR/CD155 that induces breast cancer invasion. Cell Rep. 2023 Dec.42(12):113463. Pubmedid: 37995180.
    • Adhikari E, Liu Q, Burton C, Mockabee-Macias A, Lester DK, Lau E. L-fucose, a sugary regulator of antitumor immunity and immunotherapies. Mol Carcinogen. 2022 May.61(5):439-453. Pubmedid: 35107186. Pmcid: PMC9097813.
    • Vellano CP, White MG, Andrews MC, Chelvanambi M, Witt RG, Daniele JR, Titus M, McQuade JL, Conforti F, Burton EM, Lastrapes MJ, Ologun G, Cogdill AP, Morad G, Prieto P, Lazar AJ, Chu Y, Han G, Khan MAW, Helmink B, Davies MA, Amaria RN, Kovacs JJ, Woodman SE, Patel S, Hwu P, Peoples M, Lee JE, Cooper ZA, Zhu H, Gao G, Banerjee H, Lau M, Gershenwald JE, Lucci A, Keung EZ, Ross MI, Pala L, Pagan E, Segura RL, Liu Q, Borthwick MS, Lau E, Yates MS, Westin SN, Wani K, Tetzlaff MT, Haydu LE, Mahendra M, Ma X, Logothetis C, Kulstad Z, Johnson S, Hudgens CW, Feng N, Federico L, Long GV, Futreal PA, Arur S, Tawbi HA, Moran AE, Wang L, Heffernan TP, Marszalek JR, Wargo JA. Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy. Nature. 2022 Jun.606(7915):797-803. Pubmedid: 35705814.
    • Watson G, Lester D, Ren H, Forsyth CM, Medina E, Gonzalez Perez D, Darville L, Yao J, Luca V, Koomen J, Cen L, Lau E. Fucosylated Proteome Profiling Identifies a Fucosylated, Non-Ribosomal, Stress-Responsive Species of Ribosomal Protein S3. Cells. 2021 May.10(6). Pubmedid: 34070332. Pmcid: PMC8228307.
    • Ketcher DE, Bidelman A, Le LQ, Otto AK, Lester DK, Amtmann-Beuttner KK, Gonzalez B, Wright KL, Vadaparampil ST, Reblin M, Lau EK. Partnering patients, caregivers, and basic scientists: an engagement model that fosters patient- and family-centered research culture. Transl Res. 2021 Jan.227:64-74. Pubmedid: 32739418. Pmcid: PMC7719089.
    • Emmons MF, Faião-Flores F, Sharma R, Thapa R, Messina JL, Becker JC, Schadendorf D, Seto E, Sondak VK, Koomen JM, Chen YA, Lau EK, Wan L, Licht JD, Smalley KSM. HDAC8 Regulates a Stress Response Pathway in Melanoma to Mediate Escape from BRAF Inhibitor Therapy. Cancer Res. 2019 Jun.79(11):2947-2961. Pubmedid: 30987999. Pmcid: PMC6548652.
    • Keeley TS, Yang S, Lau E. The Diverse Contributions of Fucose Linkages in Cancer. Cancers (Basel). 2019 Aug.11(9). Pubmedid: 31450600. Pmcid: PMC6769556.
    • Keeley T, Lin S, Lester DK, Lau EK, Yang S. The fucose salvage pathway inhibits invadopodia formation and extracellular matrix degradation in melanoma cells. PLoS One. 2018 Jun.13(6):e0199128. Pubmedid: 29924834. Pmcid: PMC6010265.
    • Watson G, Ronai Z, Lau E. ATF2, a paradigm of the multifaceted regulation of transcription factors in biology and disease. Pharmacol Res. 2017 May.119:347-357. Pubmedid: 28212892. Pmcid: PMC5457671.
    • Claps G, Cheli Y, Zhang T, Scortegagna M, Lau E, Kim H, Qi J, Li JL, James B, Dzung A, Levesque MP, Dummer R, Hayward NK, Bosenberg M, Brown KM, Ronai ZA. A Transcriptionally Inactive ATF2 Variant Drives Melanomagenesis. Cell Rep. 2016 May.15(9):1884-1892. Pubmedid: 27210757. Pmcid: PMC4889472.
    • Jeon YJ, Khelifa S, Ratnikov B, Scott DA, Feng Y, Parisi F, Ruller C, Lau E, Kim H, Brill LM, Jiang T, Rimm DL, Cardiff RD, Mills GB, Smith JW, Osterman AL, Kluger Y, Ronai ZA. Regulation of glutamine carrier proteins by RNF5 determines breast cancer response to ER stress-inducing chemotherapies. Cancer Cell. 2015 Mar.27(3):354-369. Pubmedid: 25759021. Pmcid: PMC4356903.
    • Lau E, Sedy J, Sander C, Shaw MA, Feng Y, Scortegagna M, Claps G, Robinson S, Cheng P, Srivas R, Soonthornvacharin S, Ideker T, Bosenberg M, Gonzalez R, Robinson W, Chanda SK, Ware C, Dummer R, Hoon D, Kirkwood JM, Ronai ZA. Transcriptional repression of IFNβ1 by ATF2 confers melanoma resistance to therapy. Oncogene. 2015 Mar. Pubmedid: 25728676. Pmcid: PMC4558399.
    • Senft D, Sorolla A, Dewing A, Claps G, Lau E, Walker GJ, Ronai ZA. ATF2 alters melanocyte response and macrophage recruitment in UV-irradiated neonatal mouse skin. Pigment Cell Melanoma Res. 2015 Jul.28(4):481-484. Pubmedid: 25963442. Pmcid: PMC4996074.
    • Feng Y, Pinkerton AB, Hulea L, Zhang T, Davies MA, Grotegut S, Cheli Y, Yin H, Lau E, Kim H, De SK, Barile E, Pellecchia M, Bosenberg M, Li JL, James B, Hassig CA, Brown KM, Topisirovic I, Ronai ZA. SBI-0640756 Attenuates the Growth of Clinically Unresponsive Melanomas by Disrupting the eIF4F Translation Initiation Complex. Cancer Res. 2015 Dec.75(24):5211-5218. Pubmedid: 26603897. Pmcid: PMC4681635.
    • Lau E, Feng Y, Claps G, Fukuda MN, Perlina A, Donn D, Jilaveanu L, Kluger H, Freeze HH, Ronai ZA. The transcription factor ATF2 promotes melanoma metastasis by suppressing protein fucosylation. Sci Signal. 2015 Dec.8(406):ra124. Pubmedid: 26645581. Pmcid: PMC4818095.
    • Scortegagna M, Lau E, Zhang T, Feng Y, Sereduk C, Yin H, De SK, Meeth K, Platt JT, Langdon CG, Halaban R, Pellecchia M, Davies MA, Brown K, Stern DF, Bosenberg M, Ronai ZA. PDK1 and SGK3 Contribute to the Growth of BRAF-Mutant Melanomas and Are Potential Therapeutic Targets. Cancer Res. 2015 Apr.75(7):1399-1412. Pubmedid: 25712345. Pmcid: PMC4383687.
    • Scortegagna M, Kim H, Li JL, Yao H, Brill LM, Han J, Lau E, Bowtell D, Haddad G, Kaufman RJ, Ronai ZA. Fine tuning of the UPR by the ubiquitin ligases Siah1/2. PLoS Genet. 2014 May.10(5):e1004348. Pubmedid: 24809345. Pmcid: PMC4014425.
    • Varsano T, Lau E, Feng Y, Garrido M, Milan L, Heynen-Genel S, Hassig CA, Ronai ZA. Inhibition of melanoma growth by small molecules that promote the mitochondrial localization of ATF2. Clin Cancer Res. 2013 May.19(10):2710-2722. Pubmedid: 23589174. Pmcid: PMC3690798.
    • Feng Y, Lau E, Scortegagna M, Ruller C, De SK, Barile E, Krajewski S, Aza-Blanc P, Williams R, Pinkerton AB, Jackson M, Chin L, Pellecchia M, Bosenberg M, Ronai ZA. Inhibition of melanoma development in the Nras((Q61K)) ::Ink4a(-/-) mouse model by the small molecule BI-69A11. Pigment Cell Melanoma Res. 2013 Jan.26(1):136-142. Pubmedid: 23035722. Pmcid: PMC3632643.
    • Rico-Bautista E, Zhu W, Kitada S, Ganapathy S, Lau E, Krajewski S, Ramirez J, Bush JA, Yuan Z, Wolf DA. Small molecule-induced mitochondrial disruption directs prostate cancer inhibition via UPR signaling. Oncotarget. 2013 Aug.4(8):1212-1229. Pubmedid: 23902736. Pmcid: PMC3787152.
    • Lau E, Ronai ZA. ATF2 - at the crossroad of nuclear and cytosolic functions. J Cell Sci. 2012 Jun.125(Pt 12):2815-2824. Pubmedid: 22685333. Pmcid: PMC3434827.
    • Lau E, Kluger H, Varsano T, Lee K, Scheffler I, Rimm DL, Ideker T, Ronai ZA. PKCε promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Cell. 2012 Feb.148(3):543-555. Pubmedid: 22304920. Pmcid: PMC3615433.
    • Lau E, Ronai Z. RAF-isotype switching: from B to C through PDE. Nat Struct Mol Biol. 2011 May.18(5):517-518. Pubmedid: 21540889. Pmcid: PMC4560464.
    • Shah M, Bhoumik A, Goel V, Dewing A, Breitwieser W, Kluger H, Krajewski S, Krajewska M, Dehart J, Lau E, Kallenberg DM, Jeong H, Eroshkin A, Bennett DC, Chin L, Bosenberg M, Jones N, Ronai ZA. A role for ATF2 in regulating MITF and melanoma development. PLoS Genet. 2010 Dec.6(12):e1001258. Pubmedid: 21203491. Pmcid: PMC3009656.
    • Lau E, Chiang GG, Abraham RT, Jiang W. Divergent S phase checkpoint activation arising from prereplicative complex deficiency controls cell survival. Mol Biol Cell. 2009 Sep.20(17):3953-3964. Pubmedid: 19587119. Pmcid: PMC2735493.
    • Tsuji T, Lau E, Chiang GG, Jiang W. The role of Dbf4/Drf1-dependent kinase Cdc7 in DNA-damage checkpoint control. Mol Cell. 2008 Dec.32(6):862-869. Pubmedid: 19111665. Pmcid: PMC4556649.
    • Lau E, Tsuji T, Guo L, Lu SH, Jiang W. The role of pre-replicative complex (pre-RC) components in oncogenesis. Faseb J. 2007 Dec.21(14):3786-3794. Pubmedid: 17690155.
    • Lau E, Jiang W. Is there a pre-RC checkpoint that cancer cells lack?. Cell Cycle. 2006 Aug.5(15):1602-1606. Pubmedid: 16880740.
    • Lau E, Zhu C, Abraham RT, Jiang W. The functional role of Cdc6 in S-G2/M in mammalian cells. EMBO Rep. 2006 Apr.7(4):425-430. Pubmedid: 16439999. Pmcid: PMC1456921.
    • Zhu C, Lau E, Schwarzenbacher R, Bossy-Wetzel E, Jiang W. Spatiotemporal control of spindle midzone formation by PRC1 in human cells. Proc Natl Acad Sci U S A. 2006 Apr.103(16):6196-6201. Pubmedid: 16603632. Pmcid: PMC1458854.
  • Grants

    • Title: Modulating dendritic cell (DC) polarization and biology with L-fucose to enhance DC vaccine efficacy
      Sponsor: Florida Biomedical Research Program (FBRP)
      PI: Le-Lau, E.
    • Title: L-fucose-mediated enrichment of memory CD4+T cells and enhanced anti-melanoma immunity
      Sponsor: Nat Institutes of Health
      PI: Le-Lau, E.
    • Title: The trouble with testosterone: delineating how androgen drives melanoma invasiveness and metastasis via fucosylation-regulated cellular adhesion
      Sponsor: Florida Biomedical Research Program (FBRP)
      PI: Le-Lau, E.
    • Title: Enhancing TIL populations and immunotherapy efficacy in melanoma by modulating fucosylation
      Sponsor: Nat Institutes of Health
      PI: Le-Lau, E.

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