Elsa Flores, PhD
![Elsa Flores](/globalassets/images/researchers_bio/FloresElsa_17085.jpg)
Elsa Flores, PhD
Program: Molecular Oncology
Research Program: Cancer Biology & Evolution Program
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Overview
The focus of my laboratory is to understand the p53 family pathway to target this pathway therapeutically in cancer. As a basic scientist, my lab has made important discoveries in understanding the functions of the p53 family and its family members, as described below. The overarching goal of my lab is to use this knowledge to target cancers with mutations in this pathway. Becoming part of the Moffitt Cancer Center is essential and offers a unique opportunity to accomplish my goals. I look forward to integrating my laboratory with others at Moffitt.
Associations
- Molecular Oncology
- Cutaneous Oncology
- Thoracic Oncology
- Cancer Biology & Evolution Program
- Lung Cancer Metabolism Working Group
- Melanoma & Skin Cancer Center of Excellence
- Lung Cancer Center of Excellence
Education & Training
Graduate:
- University of Wisconsin-Madison-McCardle Laboratory for Cancer Research, PhD - Cancer Biology
Fellowship:
- Massachusetts Institute of Technology -
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Research Interest
The main focus of my laboratory is to understand the overlapping and unique activities of the p53 family in human cancer using mouse models and patient derived tumors. p53 is commonly mutated in human cancer and has been difficult to target therapeutically in cancer. This is due to the complex network of genes regulated by p53 and the extensive interactions with its family members, p63 and p73. Prior to my work, very little was known about p63 and p73 function in cancer. We have demonstrated that p63 and p73 are required for p53 to induce apoptosis in response to DNA damage, which is critical for the response to chemo- and radiation therapy of tumors. Additionally, my laboratory generated genetically engineered mouse models mutant for isoforms of p63 and p73 and provided the first evidence that p63 and p73 are potent suppressors of tumorigenesis and metastasis. Using our mouse models we have unveiled previously unappreciated functions for TAp63, which we identified as the tumor suppressive isoform of p63 in mouse and human tumors, and ∆Np63, the oncogenic isoform, in the regulation of microRNA biogenesis, stem cell maintenance, aging, and metabolism. We have also found that TAp63 and TAp73 can compensate for p53 function in vivo and found that inhibition of ∆Np63 or ∆Np73 leads to tumor regression in p53-/- mice by upregulation of TAp63 and TAp73 function and metabolic reprogramming within those tumors. The work from my laboratory indicates that the inter-related functions of the p53 family members must be understood for effective therapy of tumors with alterations in the p53 pathway. We are poised to make further advances in understanding the molecular mechanisms employed by this gene family in multiple biological processes. We are currently using genomic approaches to understand the regulation of multiple downstream pathways of the p53 family including the functions and regulation of long non-coding RNAs in multiple cancers, stem cell regulation, and tumor metabolism.
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Publications
- Flores ER, Sawyer WG. Engineering cancer's end: An interdisciplinary approach to confront the complexities of cancer. Cancer Cell. 2024 Jul.42(7):1133-1137. Pubmedid: 38848721.
- Jinesh GG, Smallin MT, Mtchedlidze N, Godwin I, Napoli M, Hackel N, Phadke MS, Deshpande AA, Li X, Lockhart JH, Baldwin JR, Acevedo-Acevedo S, Gao Y, Reiser MA, Smalley KSM, Flores ER, Brohl AS. C19MC miRNA-520G induces SP100 antiviral gene transcription and inhibits melanin production in skin cutaneous melanoma. Genes Dis. 2024 Jan.11(1):60-63. Pubmedid: 37588194. Pmcid: PMC10425800.
- Napoli M, Deshpande AA, Chakravarti D, Rajapakshe K, Gunaratne PH, Coarfa C, Flores ER. Genome-wide p63-Target Gene Analyses Reveal TAp63/NRF2-Dependent Oxidative Stress Responses. Cancer Res Commun. 2024 Feb.4(2):264-278. Pubmedid: 38165157. Pmcid: PMC10832605.
- Yoon SJ, Combs JA, Falzone A, Prieto-Farigua N, Caldwell S, Ackerman HD, Flores ER, DeNicola GM. Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors. Cancer Res. 2023 May.83(9):1426-1442. Pubmedid: 36862034. Pmcid: PMC10152234.
- Lockhart JH, Ackerman HD, Lee K, Abdalah M, Davis AJ, Hackel N, Boyle TA, Saller J, Keske A, Hänggi K, Ruffell B, Stringfield O, Cress WD, Tan AC, Flores ER. Grading of lung adenocarcinomas with simultaneous segmentation by artificial intelligence (GLASS-AI). NPJ Precis Oncol. 2023 Jul.7(1):68. Pubmedid: 37464050. Pmcid: PMC10354042.
- Yang Y, Peng Z, Flores ER, Kleinerman ES. Pramlintide: A Novel Therapeutic Approach for Osteosarcoma through Metabolic Reprogramming. Cancers (Basel). 2022 Sep.14(17). Pubmedid: 36077845. Pmcid: PMC9454976.
- Napoli M, Wu SJ, Gore BL, Abbas HA, Lee K, Checker R, Dhar S, Rajapakshe K, Tan AC, Lee MG, Coarfa C, Flores ER. Author Correction: ΔNp63 regulates a common landscape of enhancer associated genes in non-small cell lung cancer. Nat Commun. 2022 Mar.13(1):1717. Pubmedid: 35338160. Pmcid: PMC8956651.
- Chitsazzadeh V, Nguyen TN, de Mingo Pulido A, Bittencourt BB, Du L, Adelmann CH, Rivera IO, Nguyen KA, Guerra LD, Davis A, Napoli M, Ma W, Davis RE, Rajapakshe K, Coarfa C, Flores ER, Tsai KY. miR-181a Promotes Multiple Protumorigenic Functions by Targeting TGFβR3. J Invest Dermatol. 2022 Jul.142(7):1956-1965.e2. Pubmedid: 34890627. Pmcid: PMC9174350.
- Napoli M, Wu SJ, Gore BL, Abbas H, Lee K, Checker R, Dhar S, Rajapakshe K, Tan AC, Lee MG, Coarfa C, Flores ER. ΔNp63 regulates a common landscape of enhancer associated genes in non-small cell lung cancer. Nat Commun. 2022 Feb.13(1):614. Pubmedid: 35105868. Pmcid: PMC8807845.
- Rodriguez CP, Kang H, Geiger JL, Burtness B, Chung CH, Pickering CR, Fakhry C, Le QT, Yom SS, Galloway TJ, Golemis E, Li A, Shoop J, Wong S, Mehra R, Skinner H, Saba NF, Flores ER, Myers JN, Ford JM, Karchin R, Ferris RL, Kunos C, Lynn JM, Malik S. Clinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. J Natl Cancer Inst. 2022 Dec.114(12):1619-1627. Pubmedid: 36053203. Pmcid: PMC9745425.
- Wang B, Wu HH, Abuetabh Y, Leng S, Davidge ST, Flores ER, Eisenstat DD, Leng R. p63, a key regulator of Ago2, links to the microRNA-144 cluster. Cell Death Dis. 2022 Apr.13(4):397. Pubmedid: 35459267. Pmcid: PMC9033807.
- Lee K, Lockhart JH, Xie M, Chaudhary R, Slebos RJC, Flores ER, Chung CH, Tan AC. Deep Learning of Histopathology Images at the Single Cell Level. Front Artif Intell. 2021 Sep.4:754641. Pubmedid: 34568816. Pmcid: PMC8461055.
- Napoli M, Deshpande AA, Flores ER. The Landmark Discovery That Paved the Way to a Mechanistic Understanding of P53 Gain of Function and Personalized Medicine. Cancer Res. 2021 Sep.81(17):4394-4396. Pubmedid: 34470782.
- Wu HH, Wang B, Armstrong SR, Abuetabh Y, Leng S, Roa WHY, Atfi A, Marchese A, Wilson B, Sergi C, Flores ER, Eisenstat DD, Leng RP. Hsp70 acts as a fine-switch that controls E3 ligase CHIP-mediated TAp63 and ΔNp63 ubiquitination and degradation. Nucleic Acids Res. 2021 Mar.49(5):2740-2758. Pubmedid: 33619536. Pmcid: PMC7969027.
- Jinesh GG, Napoli M, Smallin MT, Davis A, Ackerman HD, Raulji P, Montey N, Flores ER, Brohl AS. Mutant p53s and chromosome 19 microRNA cluster overexpression regulate cancer testis antigen expression and cellular transformation in hepatocellular carcinoma. Sci Rep. 2021 Jun.11(1):12673. Pubmedid: 34135394. Pmcid: PMC8209049.
- Amit M, Liu C, Mansour J, Gleber-Netto FO, Tam S, Baruch EN, Aashiq M, El-Naggar AK, Moreno AC, Rosenthal DI, Glisson BS, Ferrarotto R, Wong MK, Tsai K, Flores ER, Migden MR, Silverman DA, Li G, Khanna A, Goepfert RP, Nagarajan P, Weber RS, Myers JN, Gross ND. Elective neck dissection versus observation in patients with head and neck cutaneous squamous cell carcinoma. Cancer. 2021 Dec.127(23):4413-4420. Pubmedid: 34358340.
- Xie M, Lee K, Lockhart JH, Cukras SD, Carvajal R, Beg AA, Flores ER, Teng M, Chung CH, Tan AC. TIMEx: tumor-immune microenvironment deconvolution web-portal for bulk transcriptomics using pan-cancer scRNA-seq signatures. Bioinformatics. 2021 Apr. Pubmedid: 33901274.
- Min S, Oyelakin A, Gluck C, Bard JE, Song EC, Smalley K, Che M, Flores E, Sinha S, Romano RA. p63 and Its Target Follistatin Maintain Salivary Gland Stem/Progenitor Cell Function through TGF-β/Activin Signaling. iScience. 2020 Sep.23(9):101524. Pubmedid: 32932139. Pmcid: PMC7498843.
- Napoli M, Li X, Ackerman HD, Deshpande AA, Barannikov I, Pisegna MA, Bedrosian I, Mitsch J, Quinlan P, Thompson A, Rajapakshe K, Coarfa C, Gunaratne PH, Marchion DC, Magliocco AM, Tsai KY, Flores ER. Pan-cancer analysis reveals TAp63-regulated oncogenic lncRNAs that promote cancer progression through AKT activation. Nat Commun. 2020 Oct.11(1):5156. Pubmedid: 33056990. Pmcid: PMC7561725.
- Nguyen TN, Rajapakshe K, Nicholas C, Tordesillas L, Ehli EA, Davis CM, Coarfa C, Flores ER, Dickinson SE, Curiel-Lewandrowski C, Tsai KY. Integrative transcriptomic analysis for linking acute stress responses to squamous cell carcinoma development. Sci Rep. 2020 Oct.10(1):17209. Pubmedid: 33057049. Pmcid: PMC7560606.
- Napoli M, Flores ER. The p53 family reaches the final frontier: the variegated regulation of the dark matter of the genome by the p53 family in cancer. RNA Biol. 2020 Nov.17(11):1636-1647. Pubmedid: 31910062. Pmcid: PMC7567494.
- Kumar S, Nandi A, Mahesh A, Sinha S, Flores E, Chakrabarti R. Inducible knockout of ∆Np63 alters cell polarity and metabolism during pubertal mammary gland development. FEBS Lett. 2020 Mar.594(6):973-985. Pubmedid: 31794060. Pmcid: PMC8088331.
- Davis AJ, Tsinkevich M, Rodencal J, Abbas HA, Su XH, Gi YJ, Fang B, Rajapakshe K, Coarfa C, Gunaratne PH, Koomen JM, Tsai KY, Flores ER. TAp63-Regulated miRNAs Suppress Cutaneous Squamous Cell Carcinoma through Inhibition of a Network of Cell-Cycle Genes. Cancer Res. 2020 Jun.80(12):2484-2497. Pubmedid: 32156775. Pmcid: PMC7299759.
- Jinesh GG, Napoli M, Ackerman HD, Raulji PM, Montey N, Flores ER, Brohl AS. Regulation of MYO18B mRNA by a network of C19MC miRNA-520G, IFN-γ, CEBPB, p53 and bFGF in hepatocellular carcinoma. Sci Rep. 2020 Jul.10(1):12371. Pubmedid: 32704163. Pmcid: PMC7378193.
- Bui NHB, Napoli M, Davis AJ, Abbas HA, Rajapakshe K, Coarfa C, Flores ER. Spatiotemporal Regulation of ΔNp63 by TGFβ-Regulated miRNAs Is Essential for Cancer Metastasis. Cancer Res. 2020 Jul.80(13):2833-2847. Pubmedid: 32312834. Pmcid: PMC7385751.
- Napoli M, Flores ER. Loss of p53 protein strikes a nerve to aid tumour growth. Nature. 2020 Feb.578(7795):367-369. Pubmedid: 32066916.
- Setty BA, Jinesh GG, Arnold M, Pettersson F, Cheng CH, Cen L, Yoder SJ, Teer JK, Flores ER, Reed DR, Brohl AS. The genomic landscape of undifferentiated embryonal sarcoma of the liver is typified by C19MC structural rearrangement and overexpression combined with TP53 mutation or loss. PLoS Genet. 2020 Apr.16(4):e1008642. Pubmedid: 32310940. Pmcid: PMC7192511.
- Mohamed E, Sierra RA, Trillo-Tinoco J, Cao Y, Innamarato P, Payne KK, de Mingo Pulido A, Mandula J, Zhang S, Thevenot P, Biswas S, Abdalla SK, Costich TL, Hänggi K, Anadon CM, Flores ER, Haura EB, Mehrotra S, Pilon-Thomas S, Ruffell B, Munn DH, Cubillos-Ruiz JR, Conejo-Garcia JR, Rodriguez PC. The Unfolded Protein Response Mediator PERK Governs Myeloid Cell-Driven Immunosuppression in Tumors through Inhibition of STING Signaling. Immunity. 2020 Apr.52(4):668-682.e7. Pubmedid: 32294407. Pmcid: PMC7207019.
- Alam H, Tang M, Maitituoheti M, Dhar SS, Kumar M, Han CY, Ambati CR, Amin SB, Gu B, Chen TY, Lin YH, Chen J, Muller FL, Putluri N, Flores ER, DeMayo FJ, Baseler L, Rai K, Lee MG. KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer. Cancer Cell. 2020 Apr.37(4):599-617.e7. Pubmedid: 32243837. Pmcid: PMC7178078.
- Trillo-Tinoco J, Sierra RA, Mohamed E, Cao Y, de Mingo-Pulido Á, Gilvary DL, Anadon CM, Costich TL, Wei S, Flores ER, Ruffell B, Conejo-Garcia JR, Rodriguez PC. AMPK Alpha-1 Intrinsically Regulates the Function and Differentiation of Tumor Myeloid-Derived Suppressor Cells. Cancer Res. 2019 Oct.79(19):5034-5047. Pubmedid: 31409640. Pmcid: PMC6774829.
- Napoli M, Flores ER. Beware of thy neighbor: Senescent cancer cells feast on adjacent cells to persist. J Cell Biol. 2019 Nov.218(11):3535-3536. Pubmedid: 31628158. Pmcid: PMC6829664.
- Gunaratne PH, Pan Y, Rao AK, Lin C, Hernandez-Herrera A, Liang K, Rait AS, Venkatanarayan A, Benham AL, Rubab F, Kim SS, Rajapakshe K, Chan CK, Mangala LS, Lopez-Berestein G, Sood AK, Rowat AC, Coarfa C, Pirollo KF, Flores ER, Chang EH. Activating p53 family member TAp63: A novel therapeutic strategy for targeting p53-altered tumors. Cancer. 2019 Jul.125(14):2409-2422. Pubmedid: 31012964. Pmcid: PMC6617807.
- Jinesh GG, Flores ER, Brohl AS. Chromosome 19 miRNA cluster and CEBPB expression specifically mark and potentially drive triple negative breast cancers. PLoS One. 2018 Oct.13(10):e0206008. Pubmedid: 30335837. Pmcid: PMC6193703.
- Jiang Y, Xu E, Zhang J, Chen M, Flores E, Chen X. The Rbm38-p63 feedback loop is critical for tumor suppression and longevity. Oncogene. 2018 May.37(21):2863-2872. Pubmedid: 29520104. Pmcid: PMC5970038.
- Dhar SS, Zhao D, Lin T, Gu B, Pal K, Wu SJ, Alam H, Lv J, Yun K, Gopalakrishnan V, Flores ER, Northcott PA, Rajaram V, Li W, Shilatifard A, Sillitoe RV, Chen K, Lee MG. MLL4 Is Required to Maintain Broad H3K4me3 Peaks and Super-Enhancers at Tumor Suppressor Genes. Mol Cell. 2018 Jun.70(5):825-841.e6. Pubmedid: 29861161. Pmcid: PMC6528658.
- Alam H, Li N, Dhar SS, Wu SJ, Lv J, Chen K, Flores ER, Baseler L, Lee MG. HP1γ Promotes Lung Adenocarcinoma by Downregulating the Transcription-Repressive Regulators NCOR2 and ZBTB7A. Cancer Res. 2018 Jul.78(14):3834-3848. Pubmedid: 29764865. Pmcid: PMC6443096.
- Abbas H, Bao Bui NH, Rajapakshe K, Wong J, Gunaratne P, Tsai KY, Coarfa C, Flores ER. Distinct TP63 Isoform-Driven Transcriptional Signatures Predict Tumor Progression and Clinical Outcomes. Cancer Res. 2018 Jan.78(2):451-462. Pubmedid: 29180475. Pmcid: PMC5771893.
- Lu Y, Cao J, Napoli M, Xia Z, Zhao N, Creighton CJ, Li W, Chen X, Flores ER, McManus MT, Rosen JM. miR-205 Regulates Basal Cell Identity and Stem Cell Regenerative Potential During Mammary Reconstitution. Stem Cells. 2018 Dec.36(12):1875-1889. Pubmedid: 30267595. Pmcid: PMC6379077.
- Patel V, Singh VP, Pinnamaneni JP, Sanagasetti D, Olive J, Mathison M, Cooney A, Flores ER, Crystal RG, Yang J, Rosengart TK. p63 Silencing induces reprogramming of cardiac fibroblasts into cardiomyocyte-like cells. J Thorac Cardiovasc Surg. 2018 Aug.156(2):556-565.e1. Pubmedid: 29716728. Pmcid: PMC6050095.
- Wang C, He Y, Xu P, Yang Y, Saito K, Xia Y, Yan X, Hinton A, Yan C, Ding H, Yu L, Shu G, Gupta R, Wu Q, Tong Q, Lagor WR, Flores ER, Xu Y. TAp63 contributes to sexual dimorphism in POMC neuron functions and energy homeostasis. Nat Commun. 2018 Apr.9(1):1544. Pubmedid: 29670083. Pmcid: PMC5906443.
- Campbell JD, Yau C, Bowlby R, Liu Y, Brennan K, Fan H, Taylor AM, Wang C, Walter V, Akbani R, Byers LA, Creighton CJ, Coarfa C, Shih J, Cherniack AD, Gevaert O, Prunello M, Shen H, Anur P, Chen J, Cheng H, Hayes DN, Bullman S, Pedamallu CS, Ojesina AI, Sadeghi S, Mungall KL, Robertson AG, Benz C, Schultz A, Kanchi RS, Gay CM, Hegde A, Diao L, Wang J, Ma W, Sumazin P, Chiu HS, Chen TW, Gunaratne P, Donehower L, Rader JS, Zuna R, Al-Ahmadie H, Lazar AJ, Flores ER, Tsai KY, Zhou JH, Rustgi AK, Drill E, Shen R, Wong CK, Stuart JM, Laird PW, Hoadley KA, Weinstein JN, Peto M, Pickering CR, Chen Z, Van Waes C. Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas. Cell Rep. 2018 Apr.23(1):194-212.e6. Pubmedid: 29617660. Pmcid: PMC6002769.
- Martin-Lopez M, Maeso-Alonso L, Fuertes-Alvarez S, Balboa D, Rodríguez-Cortez V, Weltner J, Diez-Prieto I, Davis A, Wu Y, Otonkoski T, Flores ER, Menéndez P, Marques MM, Marin MC. p73 is required for appropriate BMP-induced mesenchymal-to-epithelial transition during somatic cell reprogramming. Cell Death Dis. 2017 Sep.8(9):e3034. Pubmedid: 28880267. Pmcid: PMC5636977.
- Napoli M, Flores ER. Another case for diet restriction: TAp73-expressing medulloblastomas are stunted by glutamine withdrawal. Gene Dev. 2017 Sep.31(17):1715-1716. Pubmedid: 28982757. Pmcid: PMC5666670.
- Rigoutsos I, Lee SK, Nam SY, Anfossi S, Pasculli B, Pichler M, Jing Y, Rodriguez-Aguayo C, Telonis AG, Rossi S, Ivan C, Catela Ivkovic T, Fabris L, Clark PM, Ling H, Shimizu M, Redis RS, Shah MY, Zhang X, Okugawa Y, Jung EJ, Tsirigos A, Huang L, Ferdin J, Gafà R, Spizzo R, Nicoloso MS, Paranjape AN, Shariati M, Tiron A, Yeh JJ, Teruel-Montoya R, Xiao L, Melo SA, Menter D, Jiang ZQ, Flores ER, Negrini M, Goel A, Bar-Eli M, Mani SA, Liu CG, Lopez-Berestein G, Berindan-Neagoe I, Esteller M, Kopetz S, Lanza G, Calin GA. N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration. Genome Biol. 2017 May.18(1):98. Pubmedid: 28535802. Pmcid: PMC5442648.
- Marcet-Ortega M, Pacheco S, Martínez-Marchal A, Castillo H, Flores E, Jasin M, Keeney S, Roig I. p53 and TAp63 participate in the recombination-dependent pachytene arrest in mouse spermatocytes. PLoS Genet. 2017 Jun.13(6):e1006845. Pubmedid: 28617799. Pmcid: PMC5491309.
- Napoli M, Flores ER. The p53 family orchestrates the regulation of metabolism: physiological regulation and implications for cancer therapy. Brit J Cancer. 2017 Jan.116(2):149-155. Pubmedid: 27884017. Pmcid: PMC5243983.
- Wang S, Liang K, Hu Q, Li P, Song J, Yang Y, Yao J, Mangala LS, Li C, Yang W, Park PK, Hawke DH, Zhou J, Zhou Y, Xia W, Hung MC, Marks JR, Gallick GE, Lopez-Berestein G, Flores ER, Sood AK, Huang S, Yu D, Yang L, Lin C. JAK2-binding long noncoding RNA promotes breast cancer brain metastasis. J Clin Invest. 2017 Dec.127(12):4498-4515. Pubmedid: 29130936. Pmcid: PMC5707156.
- Liao W, Liu H, Zhang Y, Jung JH, Chen J, Su X, Kim YC, Flores ER, Wang SM, Czarny-Ratajczak M, Li W, Zeng SX, Lu H. Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism. Sci Rep. 2017 Aug.7(1):9020. Pubmedid: 28827783. Pmcid: PMC5566403.
- Su X, Napoli M, Abbas HA, Venkatanarayan A, Bui NH, Coarfa C, Gi YJ, Kittrell F, Gunaratne PH, Medina D, Rosen JM, Behbod F, Flores ER. TAp63 suppresses mammary tumorigenesis through regulation of the Hippo pathway. Oncogene. 2017 Apr.36(17):2377-2393. Pubmedid: 27869165. Pmcid: PMC5415945.
- Adelmann CH, Truong KA, Liang RJ, Bansal V, Gandee L, Saporito R, Lee W, Du L, Nicholas C, Napoli M, Mino B, South AP, Proby CM, Leigh IM, Coarfa C, Flores ER, Tsai KY. MEK Is a Therapeutic and Chemopreventative Target in Squamous Cell Carcinoma. J Invest Dermatol. 2016 Sep.136(9):1920-1924. Pubmedid: 27293029. Pmcid: PMC5303342.
- Venkatanarayan A, Raulji P, Norton W, Flores ER. Novel therapeutic interventions for p53-altered tumors through manipulation of its family members, p63 and p73. Cell Cycle. 2016 Oct.15(2):164-171. Pubmedid: 26652033. Pmcid: PMC4825839.
- Matre P, Velez J, Jacamo R, Qi Y, Su X, Cai T, Chan SM, Lodi A, Sweeney SR, Ma H, Davis RE, Baran N, Haferlach T, Su X, Flores ER, Gonzalez D, Konoplev S, Samudio I, DiNardo C, Majeti R, Schimmer AD, Li W, Wang T, Tiziani S, Konopleva M. Inhibiting glutaminase in acute myeloid leukemia: metabolic dependency of selected AML subtypes. Oncotarget. 2016 Nov.7(48):79722-79735. Pubmedid: 27806325. Pmcid: PMC5340236.
- Napoli M, Venkatanarayan A, Raulji P, Meyers BA, Norton W, Mangala LS, Sood AK, Rodriguez-Aguayo C, Lopez-Berestein G, Vin H, Duvic M, Tetzlaff MB, Curry JL, Rook AH, Abbas HA, Coarfa C, Gunaratne PH, Tsai KY, Flores ER. ΔNp63/DGCR8-Dependent MicroRNAs Mediate Therapeutic Efficacy of HDAC Inhibitors in Cancer. Cancer Cell. 2016 Jun.29(6):874-888. Pubmedid: 27300436. Pmcid: PMC4908836.
- Napoli M, Flores ER. Unifying the p73 knockout phenotypes: TAp73 orchestrates multiciliogenesis. Gene Dev. 2016 Jun.30(11):1253-1254. Pubmedid: 27298333. Pmcid: PMC4911924.
- Flores ER. Commentary on "Apoptosis, p53, and Tumor Cell Sensitivity to Anticancer Agents". Cancer Res. 2016 Dec.76(23):6763-6764. Pubmedid: 27909063.
- Wang Y, Wang X, Flores ER, Yu J, Chang S. Dysfunctional telomeres induce p53-dependent and independent apoptosis to compromise cellular proliferation and inhibit tumor formation. Aging Cell. 2016 Aug.15(4):646-660. Pubmedid: 27113195. Pmcid: PMC4933665.
- Chitsazzadeh V, Coarfa C, Drummond JA, Nguyen T, Joseph A, Chilukuri S, Charpiot E, Adelmann CH, Ching G, Nguyen TN, Nicholas C, Thomas VD, Migden M, MacFarlane D, Thompson E, Shen J, Takata Y, McNiece K, Polansky MA, Abbas HA, Rajapakshe K, Gower A, Spira A, Covington KR, Xiao W, Gunaratne P, Pickering C, Frederick M, Myers JN, Shen L, Yao H, Su X, Rapini RP, Wheeler DA, Hawk ET, Flores ER, Tsai KY. Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates. Nat Commun. 2016 Aug.7:12601. Pubmedid: 27574101. Pmcid: PMC5013636.
- Wu Y, Lindblad JL, Garnett J, Kamber Kaya HE, Xu D, Zhao Y, Flores ER, Hardy J, Bergmann A. Genetic characterization of two gain-of-function alleles of the effector caspase DrICE in Drosophila. Cell Death Differ. 2016 Apr.23(4):723-732. Pubmedid: 26542461. Pmcid: PMC4986642.
- Singh MM, Johnson B, Venkatarayan A, Flores ER, Zhang J, Su X, Barton M, Lang F, Chandra J. Preclinical activity of combined HDAC and KDM1A inhibition in glioblastoma. Neurooncol. 2015 Nov.17(11):1463-1473. Pubmedid: 25795306. Pmcid: PMC4648298.
- Eskander MA, Ruparel S, Green DP, Chen PB, Por ED, Jeske NA, Gao X, Flores ER, Hargreaves KM. Persistent Nociception Triggered by Nerve Growth Factor (NGF) Is Mediated by TRPV1 and Oxidative Mechanisms. J Neurosci. 2015 Jun.35(22):8593-8603. Pubmedid: 26041925. Pmcid: PMC4452557.
- Venkatanarayan A, Raulji P, Norton W, Chakravarti D, Coarfa C, Su X, Sandur SK, Ramirez MS, Lee J, Kingsley CV, Sananikone EF, Rajapakshe K, Naff K, Parker-Thornburg J, Bankson JA, Tsai KY, Gunaratne PH, Flores ER. IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo. Nature. 2015 Jan.517(7536):626-630. Pubmedid: 25409149. Pmcid: PMC4312210.
- Tan EH, Morton JP, Timpson P, Tucci P, Melino G, Flores ER, Sansom OJ, Vousden KH, Muller PA. Functions of TAp63 and p53 in restraining the development of metastatic cancer. Oncogene. 2014 Jun.33(25):3325-3333. Pubmedid: 23873029. Pmcid: PMC4181588.
- Chakravarti D, Su X, Cho MS, Bui NH, Coarfa C, Venkatanarayan A, Benham AL, Flores González RE, Alana J, Xiao W, Leung ML, Vin H, Chan IL, Aquino A, Müller N, Wang H, Cooney AJ, Parker-Thornburg J, Tsai KY, Gunaratne PH, Flores ER. Induced multipotency in adult keratinocytes through down-regulation of ΔNp63 or DGCR8. Proc Natl Acad Sci U S A. 2014 Feb.111(5):E572-E581. Pubmedid: 24449888. Pmcid: PMC3918754.
- Chaluvally-Raghavan P, Zhang F, Pradeep S, Hamilton MP, Zhao X, Rupaimoole R, Moss T, Lu Y, Yu S, Pecot CV, Aure MR, Peuget S, Rodriguez-Aguayo C, Han HD, Zhang D, Venkatanarayan A, Krohn M, Kristensen VN, Gagea M, Ram P, Liu W, Lopez-Berestein G, Lorenzi PL, Børresen-Dale AL, Chin K, Gray J, Dusetti NJ, McGuire SE, Flores ER, Sood AK, Mills GB. Copy number gain of hsa-miR-569 at 3q26.2 leads to loss of TP53INP1 and aggressiveness of epithelial cancers. Cancer Cell. 2014 Dec.26(6):863-879. Pubmedid: 25490449. Pmcid: PMC4261159.
- Botchkarev VA, Flores ER. p53/p63/p73 in the epidermis in health and disease. Cold Spring Harb Perspect Med. 2014 Aug.4(8). Pubmedid: 25085956. Pmcid: PMC4109579.
- Vin H, Ojeda SS, Ching G, Leung ML, Chitsazzadeh V, Dwyer DW, Adelmann CH, Restrepo M, Richards KN, Stewart LR, Du L, Ferguson SB, Chakravarti D, Ehrenreiter K, Baccarini M, Ruggieri R, Curry JL, Kim KB, Ciurea AM, Duvic M, Prieto VG, Ullrich SE, Dalby KN, Flores ER, Tsai KY. BRAF inhibitors suppress apoptosis through off-target inhibition of JNK signaling. Elife. 2013 Nov.2:e00969. Pubmedid: 24192036. Pmcid: PMC3814616.
- Napoli M, Flores ER. The family that eats together stays together: new p53 family transcriptional targets in autophagy. Gene Dev. 2013 May.27(9):971-974. Pubmedid: 23651851. Pmcid: PMC3656325.
- Liao JM, Zhang Y, Liao W, Zeng SX, Su X, Flores ER, Lu H. IκB kinase β (IKKβ) inhibits p63 isoform γ (TAp63γ) transcriptional activity. J Biol Chem. 2013 Jun.288(25):18184-18193. Pubmedid: 23589370. Pmcid: PMC3689961.
- Cancino GI, Yiu AP, Fatt MP, Dugani CB, Flores ER, Frankland PW, Josselyn SA, Miller FD, Kaplan DR. p63 Regulates adult neural precursor and newly born neuron survival to control hippocampal-dependent Behavior. J Neurosci. 2013 Jul.33(31):12569-12585. Pubmedid: 23904595. Pmcid: PMC3728680.
- Tran MN, Choi W, Wszolek MF, Navai N, Lee IL, Nitti G, Wen S, Flores ER, Siefker-Radtke A, Czerniak B, Dinney C, Barton M, McConkey DJ. The p63 protein isoform ΔNp63α inhibits epithelial-mesenchymal transition in human bladder cancer cells: role of MIR-205. J Biol Chem. 2013 Feb.288(5):3275-3288. Pubmedid: 23239884. Pmcid: PMC3561548.
- Su X, Chakravarti D, Flores ER. p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis. Nat Rev Cancer. 2013 Feb.13(2):136-143. Pubmedid: 23344544. Pmcid: PMC4181578.
- Eno CO, Zhao G, Venkatanarayan A, Wang B, Flores ER, Li C. Noxa couples lysosomal membrane permeabilization and apoptosis during oxidative stress. Free Radical Bio Med. 2013 Dec.65:26-37. Pubmedid: 23770082. Pmcid: PMC3816129.
- Chari NS, Romano RA, Koster MI, Jaks V, Roop D, Flores ER, Teglund S, Sinha S, Gruber W, Aberger F, Medeiros LJ, Toftgard R, McDonnell TJ. Interaction between the TP63 and SHH pathways is an important determinant of epidermal homeostasis. Cell Death Differ. 2013 Aug.20(8):1080-1088. Pubmedid: 23686138. Pmcid: PMC3705600.
- Terrinoni A, Serra V, Bruno E, Strasser A, Valente E, Flores ER, van Bokhoven H, Lu X, Knight RA, Melino G. Role of p63 and the Notch pathway in cochlea development and sensorineural deafness. Proc Natl Acad Sci U S A. 2013 Apr.110(18):7300-7305. Pubmedid: 23589895. Pmcid: PMC3645580.
- Flores ER, Lozano G. The p53 family grows old. Gene Dev. 2012 Sep.26(18):1997-2000. Pubmedid: 22987633. Pmcid: PMC3444725.
- Ahn YH, Gibbons DL, Chakravarti D, Creighton CJ, Rizvi ZH, Adams HP, Pertsemlidis A, Gregory PA, Wright JA, Goodall GJ, Flores ER, Kurie JM. ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression. J Clin Invest. 2012 Sep.122(9):3170-3183. Pubmedid: 22850877. Pmcid: PMC3428095.
- Su X, Gi YJ, Chakravarti D, Chan IL, Zhang A, Xia X, Tsai KY, Flores ER. TAp63 is a master transcriptional regulator of lipid and glucose metabolism. Cell Metab. 2012 Oct.16(4):511-525. Pubmedid: 23040072. Pmcid: PMC3483083.
- Lee DF, Su J, Ang YS, Carvajal-Vergara X, Mulero-Navarro S, Pereira CF, Gingold J, Wang HL, Zhao R, Sevilla A, Darr H, Williamson AJ, Chang B, Niu X, Aguilo F, Flores ER, Sher YP, Hung MC, Whetton AD, Gelb BD, Moore KA, Snoeck HW, Ma'ayan A, Schaniel C, Lemischka IR. Regulation of embryonic and induced pluripotency by aurora kinase-p53 signaling. Cell Stem Cell. 2012 Aug.11(2):179-194. Pubmedid: 22862944. Pmcid: PMC3413175.
- Flores ER. p73 is critical for the persistence of memory. Cell Death Differ. 2011 Mar.18(3):381-382. Pubmedid: 21317911. Pmcid: PMC3131993.
- Mitani Y, Li J, Weber RS, Lippman SL, Flores ER, Caulin C, El-Naggar AK. Expression and regulation of the ΔN and TAp63 isoforms in salivary gland tumorigenesis clinical and experimental findings. Am J Pathol. 2011 Jul.179(1):391-399. Pubmedid: 21703418. Pmcid: PMC3123859.
- Flores ER, Halder G. Stem cell proliferation in the skin: alpha-catenin takes over the hippo pathway. Sci Signal. 2011 Jul.4(183):pe34. Pubmedid: 21791701.
- Wu H, Zeinab RA, Flores ER, Leng RP. Pirh2, a ubiquitin E3 ligase, inhibits p73 transcriptional activity by promoting its ubiquitination. Mol Cancer Res. 2011 Dec.9(12):1780-1790. Pubmedid: 21994467.
- Bornstein C, Brosh R, Molchadsky A, Madar S, Kogan-Sakin I, Goldstein I, Chakravarti D, Flores ER, Goldfinger N, Sarig R, Rotter V. SPATA18, a spermatogenesis-associated gene, is a novel transcriptional target of p53 and p63. Mol Cell Biol. 2011 Apr.31(8):1679-1689. Pubmedid: 21300779. Pmcid: PMC3126342.
- Su X, Chakravarti D, Cho MS, Liu L, Gi YJ, Lin YL, Leung ML, El-Naggar A, Creighton CJ, Suraokar MB, Wistuba I, Flores ER. TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature. 2010 Oct.467(7318):986-990. Pubmedid: 20962848. Pmcid: PMC3055799.
- Cho MS, Chan IL, Flores ER. ΔNp63 transcriptionally regulates brachyury, a gene with diverse roles in limb development, tumorigenesis and metastasis. Cell Cycle. 2010 Jun.9(12):2434-2441. Pubmedid: 20519941.
- Lin YL, Sengupta S, Gurdziel K, Bell GW, Jacks T, Flores ER. p63 and p73 transcriptionally regulate genes involved in DNA repair. PLoS Genet. 2009 Oct.5(10):e1000680. Pubmedid: 19816568. Pmcid: PMC2752189.
- Su X, Flores ER. TAp63: The fountain of youth. Aging (Albany NY). 2009 Oct.1(10):866-869. Pubmedid: 20157559. Pmcid: PMC2815729.
- Su X, Paris M, Gi YJ, Tsai KY, Cho MS, Lin YL, Biernaskie JA, Sinha S, Prives C, Pevny LH, Miller FD, Flores ER. TAp63 prevents premature aging by promoting adult stem cell maintenance. Cell Stem Cell. 2009 Jul.5(1):64-75. Pubmedid: 19570515. Pmcid: PMC3418222.
- Su X, Cho MS, Gi YJ, Ayanga BA, Sherr CJ, Flores ER. Rescue of key features of the p63-null epithelial phenotype by inactivation of Ink4a and Arf. Embo J. 2009 Jul.28(13):1904-1915. Pubmedid: 19494829. Pmcid: PMC2711186.
- Talos F, Nemajerova A, Flores ER, Petrenko O, Moll UM. p73 suppresses polyploidy and aneuploidy in the absence of functional p53. Mol Cell. 2007 Aug.27(4):647-659. Pubmedid: 17707235.
- Iwakuma T, Lozano G, Flores ER. Li-Fraumeni syndrome: a p53 family affair. Cell Cycle. 2005 Jul.4(7):865-867. Pubmedid: 15917654.
- Flores ER, Sengupta S, Miller JB, Newman JJ, Bronson R, Crowley D, Yang A, McKeon F, Jacks T. Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell. 2005 Apr.7(4):363-373. Pubmedid: 15837625.
- Reczek EE, Flores ER, Tsay AS, Attardi LD, Jacks T. Multiple response elements and differential p53 binding control Perp expression during apoptosis. Mol Cancer Res. 2003 Dec.1(14):1048-1057. Pubmedid: 14707288.
- de Vries A, Flores ER, Miranda B, Hsieh HM, van Oostrom CT, Sage J, Jacks T. Targeted point mutations of p53 lead to dominant-negative inhibition of wild-type p53 function. Proc Natl Acad Sci U S A. 2002 Mar.99(5):2948-2953. Pubmedid: 11867759. Pmcid: PMC122453.
- Flores ER, Tsai KY, Crowley D, Sengupta S, Yang A, McKeon F, Jacks T. p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature. 2002 Apr.416(6880):560-564. Pubmedid: 11932750.
- Duensing S, Duensing A, Flores ER, Do A, Lambert PF, Münger K. Centrosome abnormalities and genomic instability by episomal expression of human papillomavirus type 16 in raft cultures of human keratinocytes. J Virol. 2001 Aug.75(16):7712-7716. Pubmedid: 11462043. Pmcid: PMC115006.
- Irwin M, Marin MC, Phillips AC, Seelan RS, Smith DI, Liu W, Flores ER, Tsai KY, Jacks T, Vousden KH, Kaelin WG. Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature. 2000 Oct.407(6804):645-648. Pubmedid: 11034215.
- Flores ER, Allen-Hoffmann BL, Lee D, Lambert PF. The human papillomavirus type 16 E7 oncogene is required for the productive stage of the viral life cycle. J Virol. 2000 Jul.74(14):6622-6631. Pubmedid: 10864676. Pmcid: PMC112172.
- Flores ER, Allen-Hoffmann BL, Lee D, Sattler CA, Lambert PF. Establishment of the human papillomavirus type 16 (HPV-16) life cycle in an immortalized human foreskin keratinocyte cell line. Virology. 1999 Sep.262(2):344-354. Pubmedid: 10502513.
- Flores ER, Lambert PF. Evidence for a switch in the mode of human papillomavirus type 16 DNA replication during the viral life cycle. J Virol. 1997 Oct.71(10):7167-7179. Pubmedid: 9311789. Pmcid: PMC192056.
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Grants
- Title: Dual Up- and Downstream Targeting of POU2F3 in Small Cell Lung Cancer
Sponsor: US Army
PI: Rix, U., CO-PI: Flores, E. - Title: Community Project Funding/Congressionally Directed Spending ‐ Construction
Sponsor: Dept of Health & Human Services (DHHS)
PI: Flores, E. - Title: Novel combination approaches for targeting oncogenic signaling dependencies in POU2F3- driven small cell lung cancer
Sponsor: Florida Biomedical Research Program (FBRP)
PI (Contact): Rix, U., PI: Flores, E. - Title: Targeting "Undruggable" Pathways
Sponsor: Florida Biomedical Research Program (FBRP)
PI: Flores, E. - Title: Identifying Metabolic Vulnerabilities in Lung Cancer
Sponsor: Nat Institutes of Health
PI (Contact): Flores, E., PI (MPI): Haura, E., Project PI: DeNicola, G., Project PI: Rodriguez, P., Project PI: Cleveland, J. - Title: Integrated Program in Cancer and Data Science
Sponsor: Nat Institutes of Health
PI (Contact): Cress, D., PI (MPI): Flores, E., PI (MPI): Fridley, B.
- Title: Dual Up- and Downstream Targeting of POU2F3 in Small Cell Lung Cancer