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E. Alejandro Sweet-Cordero, MD

TitleAssociate Professor
InstitutionUniversity of California San Francisco
DepartmentPediatrics
Address1550 Fourth St
San Francisco CA 94158
Phone415-476-7781
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    Collapse Biography 
    Collapse Education and Training
    Stanford UniversityBA1989Biology
    Stanford UniversityBS1989Anthropology
    University of California San FranciscoMD1995Medicine

    Collapse Overview 
    Collapse Overview
    Our goal is to identify novel therapeutic approaches for cancer that target the genetic mutations and altered signaling networks that are specific to cancer cells. We use functional genomics applied to mouse and human systems (genetically engineered models, patient derived xenografts) to understand the transcriptional networks that regulate the outcome of specific oncogenic mutations and to identify new approaches for cancer therapy. We have two primary disease interests: lung cancer and pediatric sarcomas.

    In our lung cancer work, we are heavily focused on using functional genomic approaches to study how KRAS functions as an oncogene. For example, we carried out one of the first mouse and human combined screens to identify Wt1 as a synthetic vulnerability for KRAS in NSCLC (Vicent et al, 2010, JCI). More recently, we described a key role of oncogenic Ras in regulation of the response to nutrient stress (Gwinn et al 2018, Cancer Cell). We are funded by the NCI Ras initiative as part of a multi-PI effort to identify novel synthetic lethal genes in the Ras pathway (collaboration with the Bassik and Jackson labs, both at Stanford University). We are also interested in identifying and characterizing the role of tumor-propagating cells (also called cancer stem cells) in NSCLC. Using a combination of mouse and human systems, we identified a key role for Notch3 as a self-renewal pathway in mouse and human NSCLC (Zheng et al, 2013, Cancer Cell). Ongoing projects are seeking to identify other KRAS specific vulnerabilities using 2D and 3D systems in both mouse and human. We are also exploring the use of single cell genomics to further evaluate intra-tumor heterogeneity.

    In our sarcoma work, we are interested in mechanisms driving Osteosarcoma and Ewing sarcoma progression. These diseases provide an interesting contrast as clinically they are similar but from a genomic standpoint they are quite distinct. We recently identified EWSAT1 as the first lncRNA involved in the pathogenesis of Ewing sarcoma (Howarth et al, JCI, 2014). Ongoing work is focused on understanding how lncRNAs regulate the oncogenic capacity of the EWS/FLI1 fusion. In osteosarcoma, we are carrying out translational studies to evaluate the use of targeted therapies for this disease. Our sarcoma work is facilitated by access to a large (n>30) collection of patient-derived xenograft models. We are using these models to explore the genomic evolution of sarcomas and define novel therapeutics that are informed by the alterations present in individual tumors.

    We make extensive use of computational genomic approaches in our work and we have wide experience in generating and using next-generation sequencing data for gene and network discovery. We are actively involved in a multidisciplinary effort to apply next-generation sequencing (WGS/RNAseq etc.) to advance the care of relapsed and other high-risk pediatric cancer patients at UCSF/Benioff Children’s Hospitals (San Francisco and Oakland). To date, our laboratory has sequenced over 150 pediatric tumors by Whole Genome Sequencing and RNAseq. These datasets provide ample research opportunity for trainees interested in the intersection of cancer biology, functional genomics and computational biology.


    Collapse Research 
    Collapse Research Activities and Funding
    Development of novel protein-based therapeutics for lung cancer
    NIH R01CA225103Apr 1, 2018 - Mar 31, 2023
    Role: Principal Investigator
    Role of long non-coding RNAs in sarcoma pathogenesis
    NIH R01CA211657Mar 13, 2017 - Feb 28, 2022
    Role: Principal Investigator
    Using Protein Interaction Networks and Combinatorial Screens to target KRAS driven cancer
    NIH U01CA199216Sep 2, 2015 - Jul 31, 2019
    Role: Co-Investigator

    Collapse ORNG Applications 
    Collapse Featured Publications
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    Collapse Featured Presentations

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Gwinn DM, Lee AG, Briones-Martin-Del-Campo M, Conn CS, Simpson DR, Scott AI, Le A, Cowan TM, Ruggero D, Sweet-Cordero E. Oncogenic KRAS Regulates Amino Acid Homeostasis and Asparagine Biosynthesis via ATF4 and Alters Sensitivity to L-Asparaginase. Cancer Cell. 2018 Jan 08; 33(1):91-107.e6. PMID: 29316436.
      View in: PubMed
    2. Hsieh G, Bierman R, Szabo L, Lee AG, Freeman DE, Watson N, Sweet-Cordero E, Salzman J. Statistical algorithms improve accuracy of gene fusion detection. Nucleic Acids Res. 2017 Jul 27; 45(13):e126. PMID: 28541529.
      View in: PubMed
    3. Vallejo A, Perurena N, Guruceaga E, Mazur PK, Martinez-Canarias S, Zandueta C, Valencia K, Arricibita A, Gwinn D, Sayles LC, Chuang CH, Guembe L, Bailey P, Chang DK, Biankin A, Ponz-Sarvise M, Andersen JB, Khatri P, Bozec A, Sweet-Cordero E, Sage J, Lecanda F, Vicent S. An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer. Nat Commun. 2017 Feb 21; 8:14294. PMID: 28220783.
      View in: PubMed
    4. Chuang CH, Greenside PG, Rogers ZN, Brady JJ, Yang D, Ma RK, Caswell DR, Chiou SH, Winters AF, Grüner BM, Ramaswami G, Spencley AL, Kopecky KE, Sayles LC, Sweet-Cordero E, Li JB, Kundaje A, Winslow MM. Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis. Nat Med. 2017 Mar; 23(3):291-300. PMID: 28191885.
      View in: PubMed
    5. Brady JJ, Chuang CH, Greenside PG, Rogers ZN, Murray CW, Caswell DR, Hartmann U, Connolly AJ, Sweet-Cordero E, Kundaje A, Winslow MM. An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency. Cancer Cell. 2016 05 09; 29(5):697-710. PMID: 27150038; PMCID: PMC4864124 [Available on 05/09/17].
    6. Mazur PK, Herner A, Mello SS, Wirth M, Hausmann S, Sánchez-Rivera FJ, Lofgren SM, Kuschma T, Hahn SA, Vangala D, Trajkovic-Arsic M, Gupta A, Heid I, Noël PB, Braren R, Erkan M, Kleeff J, Sipos B, Sayles LC, Heikenwalder M, Heßmann E, Ellenrieder V, Esposito I, Jacks T, Bradner JE, Khatri P, Sweet-Cordero E, Attardi LD, Schmid RM, Schneider G, Sage J, Siveke JT. Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma. Nat Med. 2015 Oct; 21(10):1163-71. PMID: 26390243; PMCID: PMC4959788.
    7. Marques Howarth M, Simpson D, Ngok SP, Nieves B, Chen R, Siprashvili Z, Vaka D, Breese MR, Crompton BD, Alexe G, Hawkins DS, Jacobson D, Brunner AL, West R, Mora J, Stegmaier K, Khavari P, Sweet-Cordero E. Long noncoding RNA EWSAT1-mediated gene repression facilitates Ewing sarcoma oncogenesis. J Clin Invest. 2014 Dec; 124(12):5275-90. PMID: 25401475.
      View in: PubMed
    8. Chen R, Khatri P, Mazur PK, Polin M, Zheng Y, Vaka D, Hoang CD, Shrager J, Xu Y, Vicent S, Butte AJ, Sweet-Cordero E. A meta-analysis of lung cancer gene expression identifies PTK7 as a survival gene in lung adenocarcinoma. Cancer Res. 2014 May 15; 74(10):2892-902. PMID: 24654231.
      View in: PubMed
    9. Valdmanis PN, Roy-Chaudhuri B, Kim HK, Sayles LC, Zheng Y, Chuang CH, Caswell DR, Chu K, Zhang Y, Winslow MM, Sweet-Cordero E, Kay MA. Upregulation of the microRNA cluster at the Dlk1-Dio3 locus in lung adenocarcinoma. Oncogene. 2015 Jan 02; 34(1):94-103. PMID: 24317514; PMCID: PMC4065842.
    10. Zheng Y, de la Cruz CC, Sayles LC, Alleyne-Chin C, Vaka D, Knaak TD, Bigos M, Xu Y, Hoang CD, Shrager JB, Fehling HJ, French D, Forrest W, Jiang Z, Carano RA, Barck KH, Jackson EL, Sweet-Cordero E. A rare population of CD24(+)ITGB4(+)Notch(hi) cells drives tumor propagation in NSCLC and requires Notch3 for self-renewal. Cancer Cell. 2013 Jul 08; 24(1):59-74. PMID: 23845442.
      View in: PubMed
    11. Chen R, Sweet-Cordero E. Two is better than one: combining IGF1R and MEK blockade as a promising novel treatment strategy against KRAS-mutant lung cancer. Cancer Discov. 2013 May; 3(5):491-3. PMID: 23658296.
      View in: PubMed
    12. Gwinn D, Sweet-Cordero E. The phosphatase PP2A links glutamine to the tumor suppressor p53. Mol Cell. 2013 Apr 25; 50(2):157-8. PMID: 23622513.
      View in: PubMed
    13. Zheng Y, Moore H, Piryatinska A, Solis T, Sweet-Cordero E. Mathematical modeling of tumor cell proliferation kinetics and label retention in a mouse model of lung cancer. Cancer Res. 2013 Jun 15; 73(12):3525-33. PMID: 23576555; PMCID: PMC3703454.
    14. Hegde GV, de la Cruz CC, Chiu C, Alag N, Schaefer G, Crocker L, Ross S, Goldenberg D, Merchant M, Tien J, Shao L, Roth L, Tsai SP, Stawicki S, Jin Z, Wyatt SK, Carano RA, Zheng Y, Sweet-Cordero E, Wu Y, Jackson EL. Blocking NRG1 and other ligand-mediated Her4 signaling enhances the magnitude and duration of the chemotherapeutic response of non-small cell lung cancer. Sci Transl Med. 2013 Feb 06; 5(171):171ra18. PMID: 23390248.
      View in: PubMed
    15. Hegde GV, de la Cruz C, Eastham-Anderson J, Zheng Y, Sweet-Cordero E, Jackson EL. Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity. PLoS One. 2012; 7(10):e45647. PMID: 23115623; PMCID: PMC3480356.
    16. Vicent S, Sayles LC, Vaka D, Khatri P, Gevaert O, Chen R, Zheng Y, Gillespie AK, Clarke N, Xu Y, Shrager J, Hoang CD, Plevritis S, Butte AJ, Sweet-Cordero E. Cross-species functional analysis of cancer-associated fibroblasts identifies a critical role for CLCF1 and IL-6 in non-small cell lung cancer in vivo. Cancer Res. 2012 Nov 15; 72(22):5744-56. PMID: 22962265; PMCID: PMC3856949.
    17. Vicent S, Chen R, Sayles LC, Lin C, Walker RG, Gillespie AK, Subramanian A, Hinkle G, Yang X, Saif S, Root DE, Huff V, Hahn WC, Sweet-Cordero E. Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models. J Clin Invest. 2010 Nov; 120(11):3940-52. PMID: 20972333; PMCID: PMC2965578.
    18. Schaffer BE, Park KS, Yiu G, Conklin JF, Lin C, Burkhart DL, Karnezis AN, Sweet-Cordero E, Sage J. Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma. Cancer Res. 2010 May 15; 70(10):3877-83. PMID: 20406986; PMCID: PMC2873158.
    19. Oliver TG, Mercer KL, Sayles LC, Burke JR, Mendus D, Lovejoy KS, Cheng MH, Subramanian A, Mu D, Powers S, Crowley D, Bronson RT, Whittaker CA, Bhutkar A, Lippard SJ, Golub T, Thomale J, Jacks T, Sweet-Cordero E. Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer. Genes Dev. 2010 Apr 15; 24(8):837-52. PMID: 20395368; PMCID: PMC2854397.
    20. Sweet-Cordero E, Tseng GC, You H, Douglass M, Huey B, Albertson D, Jacks T. Comparison of gene expression and DNA copy number changes in a murine model of lung cancer. Genes Chromosomes Cancer. 2006 Apr; 45(4):338-48. PMID: 16323170.
      View in: PubMed
    21. Sweet-Cordero E, Mukherjee S, Subramanian A, You H, Roix JJ, Ladd-Acosta C, Mesirov J, Golub TR, Jacks T. An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis. Nat Genet. 2005 Jan; 37(1):48-55. PMID: 15608639.
      View in: PubMed