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Florian  Karreth

Florian Karreth, PhD


Program: Molecular Oncology

Research Program: Cancer Biology & Evolution Program

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  • Overview

    My lab is interested in the intersection of oncogenic signaling pathways and non-coding RNAs in the initiation, progression, and resistance of cancers driven by the MAPK pathway, with an emphasis on melanoma. We study how secondary genetic events enhance or cooperate with the MAPK pathway to promote the oncogenic evolution of melanoma. Such secondary events may represent targetable vulnerabilities that could be therapeutically explored in combination with current standard-of-care targeted therapy or immunotherapy.


    • Molecular Oncology
    • Cutaneous Oncology
    • Cancer Biology & Evolution Program
    • Melanoma & Skin Cancer Center of Excellence

    Education & Training


    • University of Vienna, MS - Genetics & Biochemistry
    • University of Vienna, PhD - Genetics


    • Beth Israel Deaconess Medical Center -
    • Weill Cornell Medical College -
  • Research Interest

    My lab is interested in the intersection of oncogenic signaling pathways and non-coding RNAs in the initiation, progression, and resistance of cancers driven by the MAPK pathway, with an emphasis on melanoma. We study how secondary genetic events enhance or cooperate with the MAPK pathway to promote the oncogenic evolution of melanoma. Such secondary events may represent targetable vulnerabilities that could be therapeutically explored in combination with current standard-of-care targeted therapy or immunotherapy.

  • Publications

    • Xu X, Bok I, Jasani N, Wang K, Chadourne M, Mecozzi N, Deng O, Welsh EA, Kinose F, Rix U, Karreth FA. PTEN Lipid Phosphatase Activity Suppresses Melanoma Formation by Opposing an AKT/mTOR/FRA1 Signaling Axis. Cancer Res. 2024 Feb.84(3):388-404. Pubmedid: 38193852. Pmcid: PMC10842853.
    • Jasani N, Xu X, Posorske B, Kim Y, Vera O, Tsai KY, DeNicola GM, Karreth FA. MAPK-mediated PHGDH induction is essential for melanoma formation and represents an actionable vulnerability. bioRxiv. 2024 Apr. Pubmedid: 38659816. Pmcid: PMC11042198.
    • DeBlasi JM, Falzone A, Caldwell S, Prieto-Farigua N, Prigge JR, Schmidt EE, Chio IIC, Karreth FA, DeNicola GM. Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation and Progression. Cancer Res. 2023 Jun.83(12):1953-1967. Pubmedid: 37062029. Pmcid: PMC10267679.
    • Tasoulas J, Srivastava S, Xu X, Tarasova V, Maniakas A, Karreth FA, Amelio AL. Genetically engineered mouse models of head and neck cancers. Oncogene. 2023 Aug.42(35):2593-2609. Pubmedid: 37474617. Pmcid: PMC10457205.
    • Xu X, Wang K, Vera O, Verma A, Jasani N, Bok I, Elemento O, Du D, Yu X, Karreth FA. Gain of Chromosome 1q Perturbs a Competitive Endogenous RNA Network to Promote Melanoma Metastasis. Cancer Res. 2022 Sep.82(17):3016-3031. Pubmedid: 36052492. Pmcid: PMC9971359.
    • Li J, Smalley I, Chen Z, Wu JY, Phadke MS, Teer JK, Nguyen T, Karreth FA, Koomen JM, Sarnaik AA, Zager JS, Khushalani NI, Tarhini AA, Sondak VK, Rodriguez PC, Messina JL, Chen YA, Smalley KSM. Single-cell Characterization of the Cellular Landscape of Acral Melanoma Identifies Novel Targets for Immunotherapy. Clin Cancer Res. 2022 May.28(10):2131-2146. Pubmedid: 35247927. Pmcid: PMC9106889.
    • Bok I, Angarita A, Douglass SM, Weeraratna AT, Karreth FA. A Series of BRAF- and NRAS-Driven Murine Melanoma Cell Lines with Inducible Gene Modulation Capabilities. JID Innov. 2022 Mar.2(2):100076. Pubmedid: 35146482. Pmcid: PMC8819036.
    • Nakamura K, Reid BM, Chen A, Chen Z, Goode EL, Permuth JB, Teer JK, Tyrer J, Yu X, Kanetsky PA, Pharoah PD, Gayther SA, Sellers TA, Lawrenson K, Karreth FA. Functional analysis of the 1p34.3 risk locus implicates GNL2 in high-grade serous ovarian cancer. Am J Hum Genet. 2022 Jan.109(1):116-135. Pubmedid: 34965383. Pmcid: PMC8764204.
    • Mecozzi N, Nenci A, Vera O, Bok I, Falzone A, DeNicola GM, Karreth FA. Genetic tools for the stable overexpression of circular RNAs. RNA Biol. 2022 Jan.19(1):353-363. Pubmedid: 35289721. Pmcid: PMC8928841.
    • Mecozzi N, Vera O, Karreth FA. Squaring the circle: circRNAs in melanoma. Oncogene. 2021 Sep.40(37):5559-5566. Pubmedid: 34331015. Pmcid: PMC8521449.
    • Grammatikakis I, Karreth FA, Panda AC. Editorial: Structural and Functional Characterization of Circular RNAs. Front Mol Biosci. 2021 Nov.8:795286. Pubmedid: 34796203. Pmcid: PMC8592900.
    • Patton EE, Mueller KL, Adams DJ, Anandasabapathy N, Aplin AE, Bertolotto C, Bosenberg M, Ceol CJ, Chi P, Burd CE, Herlyn M, Holmen SL, Karreth FA, Kaufman CK, Khan S, Kobold S, Leucci E, Levy C, Lombard DB, Lund AW, Marie KL, Marine JC, Marais R, McMahon M, Robles-Espinoza CD, Ronai ZA, Samuels Y, Soengas MS, Villanueva J, Weeraratna AT, White RM, Yeh I, Zhu J, Zon LI, Hurlbert MS, Merlino G. Melanoma models for the next generation of therapies. Cancer Cell. 2021 May.39(5):610-631. Pubmedid: 33545064. Pmcid: PMC8378471.
    • Vera O, Bok I, Jasani N, Nakamura K, Xu X, Mecozzi N, Angarita A, Wang K, Tsai KY, Karreth FA. A MAPK/miR-29 Axis Suppresses Melanoma by Targeting MAFG and MYBL2. Cancers (Basel). 2021 Mar.13(6). Pubmedid: 33808771. Pmcid: PMC8003541.
    • Bok I, Karreth FA. Strategies to Study the Functions of Pseudogenes in Mouse Models of Cancer. Methods Mol Biol. 2021 Jun.2324:287-304. Pubmedid: 34165722.
    • Xu X, Karreth FA. Pseudogenes as Competitive Endogenous RNAs: Testing miRNA Dependency. Methods Mol Biol. 2021 Jun.2324:131-147. Pubmedid: 34165713.
    • Karreth FA, Ala U, Provero P, Pandolfi PP. Pseudogenes as Competitive Endogenous RNAs: Target Prediction and Validation. Methods Mol Biol. 2021 Jun.2324:115-129. Pubmedid: 34165712.
    • Smalley KSM, Teer JK, Chen YA, Wu JY, Yao J, Koomen JM, Chen WS, Rodriguez-Waitkus P, Karreth FA, Messina JL. A Mutational Survey of Acral Nevi. JAMA Dermatol. 2021 Jul.157(7):831-835. Pubmedid: 33978681. Pmcid: PMC8117064.
    • Kang YP, Falzone A, Liu M, González-Sánchez P, Choi BH, Coloff JL, Saller JJ, Karreth FA, DeNicola GM. PHGDH supports liver ceramide synthesis and sustains lipid homeostasis. Cancer Metab. 2020 Jun.8:6. Pubmedid: 32549981. Pmcid: PMC7294658.
    • Bok I, Vera O, Xu X, Jasani N, Nakamura K, Reff J, Nenci A, Gonzalez JG, Karreth FA. A Versatile ES Cell-Based Melanoma Mouse Modeling Platform. Cancer Res. 2020 Feb.80(4):912-921. Pubmedid: 31744817. Pmcid: PMC7024666.
    • Chen YA, Teer JK, Eroglu Z, Wu JY, Koomen JM, Karreth FA, Messina JL, Smalley KSM. Translational pathology, genomics and the development of systemic therapies for acral melanoma. Semin Cancer Biol. 2020 Apr.61:149-157. Pubmedid: 31689494. Pmcid: PMC7771370.
    • Eroglu Z, Holmen SL, Chen Q, Khushalani NI, Amaravadi R, Thomas R, Ahmed KA, Tawbi H, Chandra S, Markowitz J, Smalley I, Liu JKC, Ann Chen Y, Najjar YG, Karreth FA, Abate-Daga D, Glitza IC, Sosman JA, Sondak VK, Bosenberg M, Herlyn M, Atkins MB, Kluger H, Margolin K, Forsyth PA, Davies MA, Smalley KSM. Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities. Pigment Cell Melanoma Res. 2019 May.32(3):458-469. Pubmedid: 30712316. Pmcid: PMC7771318.
    • Vera O, Rodriguez-Antolin C, de Castro J, Karreth FA, Sellers TA, de Caceres II. An epigenomic approach to identifying differential overlapping and cis-acting lncRNAs in cisplatin-resistant cancer cells. Epigenetics. 2019 Feb.13(3):251-263. Pubmedid: 29436261. Pmcid: PMC5997141.
    • Karreth FA. A Roadmap for the Computational Prediction and Experimental Validation of Competitive Endogenous RNAs. Methods Mol Biol. 2019 Apr.1970:237-250. Pubmedid: 30963496.
    • Liu H, Murphy CJ, Karreth FA, Emdal KB, White FM, Elemento O, Toker A, Wulf GM, Cantley LC. Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple-Negative Breast Cancer. Cancer Discov. 2018 Mar.8(3):354-369. Pubmedid: 29203461. Pmcid: PMC5907916.
    • Permuth JB, Chen DT, Yoder SJ, Li J, Smith AT, Choi JW, Kim J, Balagurunathan Y, Jiang K, Coppola D, Centeno BA, Klapman J, Hodul P, Karreth FA, Trevino JG, Merchant N, Magliocco A, Malafa MP, Gillies R. Linc-ing Circulating Long Non-coding RNAs to the Diagnosis and Malignant Prediction of Intraductal Papillary Mucinous Neoplasms of the Pancreas. Sci Rep. 2017 Sep.7(1):10484. Pubmedid: 28874676. Pmcid: PMC5585319.
    • Yoon SO, Shin S, Karreth FA, Buel GR, Jedrychowski MP, Plas DR, Dedhar S, Gygi SP, Roux PP, Dephoure N, Blenis J. Focal Adhesion- and IGF1R-Dependent Survival and Migratory Pathways Mediate Tumor Resistance to mTORC1/2 Inhibition. Mol Cell. 2017 Aug.67(3):512-527.e4. Pubmedid: 28757207. Pmcid: PMC5698809.
    • DeNicola GM, Karreth FA, Adams DJ, Wong CC. The utility of transposon mutagenesis for cancer studies in the era of genome editing. Genome Biol. 2015 Oct.16:229. Pubmedid: 26481584. Pmcid: PMC4612416.
    • Perna D, Karreth FA, Rust AG, Perez-Mancera PA, Rashid M, Iorio F, Alifrangis C, Arends MJ, Bosenberg MW, Bollag G, Tuveson DA, Adams DJ. BRAF inhibitor resistance mediated by the AKT pathway in an oncogenic BRAF mouse melanoma model. Proc Natl Acad Sci U S A. 2015 Feb.112(6):E536-E545. Pubmedid: 25624498. Pmcid: PMC4330752.
    • Karreth FA, Reschke M, Ruocco A, Ng C, Chapuy B, Léopold V, Sjoberg M, Keane TM, Verma A, Ala U, Tay Y, Wu D, Seitzer N, Velasco-Herrera Mdel C, Bothmer A, Fung J, Langellotto F, Rodig SJ, Elemento O, Shipp MA, Adams DJ, Chiarle R, Pandolfi PP. The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell. 2015 Apr.161(2):319-332. Pubmedid: 25843629. Pmcid: PMC6922011.
    • Tay Y, Karreth FA, Pandolfi PP. Aberrant ceRNA activity drives lung cancer. Cell Res. 2014 Mar.24(3):259-260. Pubmedid: 24525785. Pmcid: PMC3945890.
    • Tay Y, Tan SM, Karreth FA, Lieberman J, Pandolfi PP. Characterization of dual PTEN and p53-targeting microRNAs identifies microRNA-638/Dnm2 as a two-hit oncogenic locus. Cell Rep. 2014 Aug.8(3):714-722. Pubmedid: 25088422. Pmcid: PMC4128194.
    • Sadow PM, Priolo C, Nanni S, Karreth FA, Duquette M, Martinelli R, Husain A, Clohessy J, Kutzner H, Mentzel T, Carman CV, Farsetti A, Henske EP, Palescandolo E, Macconaill LE, Chung S, Fadda G, Lombardi CP, De Angelis AM, Durante O, Parker JA, Pontecorvi A, Dvorak HF, Fletcher C, Pandolfi PP, Lawler J, Nucera C. Role of BRAFV600E in the first preclinical model of multifocal infiltrating myopericytoma development and microenvironment. J Natl Cancer Inst. 2014 Aug.106(8). Pubmedid: 25063326. Pmcid: PMC4155429.
    • Karreth FA, Tay Y, Pandolfi PP. Target competition: transcription factors enter the limelight. Genome Biol. 2014 Apr.15(4):114. Pubmedid: 25001290. Pmcid: PMC4052382.
    • Karreth FA, Pandolfi PP. ceRNA cross-talk in cancer: when ce-bling rivalries go awry. Cancer Discov. 2013 Oct.3(10):1113-1121. Pubmedid: 24072616. Pmcid: PMC3801300.
    • Ala U, Karreth FA, Bosia C, Pagnani A, Taulli R, Léopold V, Tay Y, Provero P, Zecchina R, Pandolfi PP. Integrated transcriptional and competitive endogenous RNA networks are cross-regulated in permissive molecular environments. Proc Natl Acad Sci U S A. 2013 Apr.110(18):7154-7159. Pubmedid: 23536298. Pmcid: PMC3645534.
    • Gopinathan A, Denicola GM, Frese KK, Cook N, Karreth FA, Mayerle J, Lerch MM, Reinheckel T, Tuveson DA. Cathepsin B promotes the progression of pancreatic ductal adenocarcinoma in mice. Gut. 2012 Jun.61(6):877-884. Pubmedid: 22157328.
    • Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, Karreth F, Poliseno L, Provero P, Di Cunto F, Lieberman J, Rigoutsos I, Pandolfi PP. Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell. 2011 Oct.147(2):344-357. Pubmedid: 22000013. Pmcid: PMC3235920.
    • Karreth FA, Tay Y, Perna D, Ala U, Tan SM, Rust AG, DeNicola G, Webster KA, Weiss D, Perez-Mancera PA, Krauthammer M, Halaban R, Provero P, Adams DJ, Tuveson DA, Pandolfi PP. In vivo identification of tumor- suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell. 2011 Oct.147(2):382-395. Pubmedid: 22000016. Pmcid: PMC3236086.
    • Karreth FA, Frese KK, DeNicola GM, Baccarini M, Tuveson DA. C-Raf is required for the initiation of lung cancer by K-Ras(G12D). Cancer Discov. 2011 Jul.1(2):128-136. Pubmedid: 22043453. Pmcid: PMC3203527.
    • DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, Mangal D, Yu KH, Yeo CJ, Calhoun ES, Scrimieri F, Winter JM, Hruban RH, Iacobuzio-Donahue C, Kern SE, Blair IA, Tuveson DA. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature. 2011 Jul.475(7354):106-109. Pubmedid: 21734707. Pmcid: PMC3404470.
    • Meixner A, Karreth F, Kenner L, Penninger JM, Wagner EF. Jun and JunD-dependent functions in cell proliferation and stress response. Cell Death Differ. 2010 Sep.17(9):1409-1419. Pubmedid: 20300111.
    • Skoulidis F, Cassidy LD, Pisupati V, Jonasson JG, Bjarnason H, Eyfjord JE, Karreth FA, Lim M, Barber LM, Clatworthy SA, Davies SE, Olive KP, Tuveson DA, Venkitaraman AR. Germline Brca2 heterozygosity promotes Kras(G12D) -driven carcinogenesis in a murine model of familial pancreatic cancer. Cancer Cell. 2010 Nov.18(5):499-509. Pubmedid: 21056012.
    • Karreth FA, DeNicola GM, Winter SP, Tuveson DA. C-Raf inhibits MAPK activation and transformation by B-Raf(V600E). Mol Cell. 2009 Nov.36(3):477-486. Pubmedid: 19917255.
    • Karreth FA, Tuveson DA. Modelling oncogenic Ras/Raf signalling in the mouse. Curr Opin Genet Dev. 2009 Feb.19(1):4-11. Pubmedid: 19201597. Pmcid: PMC3389704.
    • King AJ, Patrick DR, Batorsky RS, Ho ML, Do HT, Zhang SY, Kumar R, Rusnak DW, Takle AK, Wilson DM, Hugger E, Wang L, Karreth F, Lougheed JC, Lee J, Chau D, Stout TJ, May EW, Rominger CM, Schaber MD, Luo L, Lakdawala AS, Adams JL, Contractor RG, Smalley KS, Herlyn M, Morrissey MM, Tuveson DA, Huang PS. Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885. Cancer Res. 2006 Dec.66(23):11100-11105. Pubmedid: 17145850.
    • Karreth F, Tuveson DA. Twist induces an epithelial-mesenchymal transition to facilitate tumor metastasis. Cancer Biol Ther. 2004 Nov.3(11):1058-1059. Pubmedid: 15640618.
    • Karreth F, Hoebertz A, Scheuch H, Eferl R, Wagner EF. The AP1 transcription factor Fra2 is required for efficient cartilage development. Development. 2004 Nov.131(22):5717-5725. Pubmedid: 15509771.
    • Meixner A, Karreth F, Kenner L, Wagner EF. JunD regulates lymphocyte proliferation and T helper cell cytokine expression. Embo J. 2004 Mar.23(6):1325-1335. Pubmedid: 15029240. Pmcid: PMC381408.
    • Eferl R, Hoebertz A, Schilling AF, Rath M, Karreth F, Kenner L, Amling M, Wagner EF. The Fos-related antigen Fra-1 is an activator of bone matrix formation. Embo J. 2004 Jul.23(14):2789-2799. Pubmedid: 15229648. Pmcid: PMC514946.
    • Gruber R, Karreth F, Kandler B, Fuerst G, Rot A, Fischer MB, Watzek G. Platelet-released supernatants increase migration and proliferation, and decrease osteogenic differentiation of bone marrow-derived mesenchymal progenitor cells under in vitro conditions. Platelets. 2004 Feb.15(1):29-35. Pubmedid: 14985174.
    • Kenner L, Hoebertz A, Beil FT, Beil T, Keon N, Karreth F, Eferl R, Scheuch H, Szremska A, Amling M, Schorpp-Kistner M, Angel P, Wagner EF. Mice lacking JunB are osteopenic due to cell-autonomous osteoblast and osteoclast defects. J Cell Biol. 2004 Feb.164(4):613-623. Pubmedid: 14769860. Pmcid: PMC2171977.
    • Gruber R, Karreth F, Frommlet F, Fischer MB, Watzek G. Platelets are mitogenic for periosteum-derived cells. J Orthop Res. 2003 Sep.21(5):941-948. Pubmedid: 12919885.
    • Gruber R, Schöfnagl M, Karreth F, Fischer MB, Watzek G. The stable analog carbocyclic TXA2 but not platelet-released TXA2 induces osteoclast-like cell formation. Prostag Leukotr Ess. 2003 Apr.68(4):267-272. Pubmedid: 12628222.
    • Gruber R, Karreth F, Fischer MB, Watzek G. Platelet-released supernatants stimulate formation of osteoclast-like cells through a prostaglandin/RANKL-dependent mechanism. Bone. 2002 May.30(5):726-732. Pubmedid: 11996911.
  • Grants

    • Title: Elucidating the oncogenic role of sMAF proteins in melanoma (supplement)
      Sponsor: Amer Cancer Society
      PI: Karreth, F.
    • Title: Defining the non-canonical functions of MYBL2 in melanoma progression
      Sponsor: Florida Biomedical Research Program (FBRP)
      PI: Karreth, F.
    • Title: Targeting a PHGDH Metabolic Vulnerability in Melanoma
      Sponsor: Nat Institutes of Health
      PI: Karreth, F.
    • Title: Novel genetic mouse models of uveal melanoma progression and metastasis
      Sponsor: US Army
      PI: Karreth, F.
    • Title: Defining the glyco-RNAome in melanoma progression
      Sponsor: US Army
      PI: Karreth, F.
    • Title: Elucidating the Oncogenic Role of sMAF Proteins in Melanoma
      Sponsor: Amer Cancer Society
      PI: Karreth, F.
    • Title: Chromosome 1q ceRNAs in melanoma progression and metastasis
      Sponsor: Nat Institutes of Health
      PI: Karreth, F.

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