Research Summary

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.  Our research spans the continuum from basic discovery to clinical application, done in a dynamic and interactive environment that is highly collaborative. 

In our lung cancer work, we use functional genomic approaches to study how KRAS functions as an oncogene and to identify novel therapeutic opportunities. We performed one of the first mouse and human in vivo functional screens to identify WT1 loss as a synthetic vulnerability for KRAS-driven NSCLC (Vicent et al, 2010, JCI). More recently, we described a key role of oncogenic KRAS in regulation of the response to nutrient stress (Gwinn et al 2018, Cancer Cell). Through a multidisciplinary collaboration we have performed a high-throughput proteomic and genomics screen to characterize novel KRAS specific combinatorial vulnerabilities (Kelly, Kostyrko and Han, Cancer Discovery 2020). 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).  We also have identified novel methods for targeting tumor-stroma interactions in lung cancer (Kim and Marquez et al, Nature Medicine, 2019). Ongoing projects are seeking to identify other KRAS specific vulnerabilities using 2D and 3D systems in both mouse and human. We are also using single-cell sequencing and other genomics approaches (ATACseq, etc) to study the role of TPCs in lung cancer. 

In our sarcoma work, we study mechanisms driving sarcoma progression using in vivo patient-derived xenograft models. We identified EWSAT1 as the first lncRNA involved in the pathogenesis of Ewing sarcoma (Howarth et al, JCI, 2014) and ongoing work is focused on understanding how lncRNAs regulate oncogenesis in sarcomas. Recently we described how genomic analysis of osteosarcoma can help identify targeted therapies for this disease (Sayles and Breese et al, Cancer Discovery 2019). Our sarcoma work is facilitated by access to a large collection of patient-derived xenograft models and to primary tumor samples.  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. These datasets provide ample research opportunity for trainees interested in the intersection of cancer biology, functional genomics and computational biology. 

E. Alejandro Sweet-Cordero is a member of both the Biomedical Sciences (BMS) and the Pharmaceutical Sciences and Pharmacogenomics (PSPG) graduate programs. The laboratory is also affiliated with the Bakar Institute for Computational Health Sciences at UCSF. Alejandro Sweet-Cordero also directs the Molecular Oncology Initiative at UCSF and has expertise in the clinical implementation of precision medicine for adult and pediatric cancer.

Individuals interested in joining our research group are encouraged to forward a Curriculum Vitae to [email protected]. For more information please refer to the lab website at sweetcorderolab.ucsf.edu
 

Research Funding

  • April 1, 2018 - March 31, 2023 - Development of novel protein-based therapeutics for lung cancer, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01CA225103
  • March 13, 2017 - February 28, 2022 - Role of long non-coding RNAs in sarcoma pathogenesis, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01CA211657
  • September 2, 2015 - July 31, 2019 - Using Protein Interaction Networks and Combinatorial Screens to target KRAS driven cancer, Co-Investigator. Sponsor: NIH, Sponsor Award ID: U01CA199216
  • April 1, 2018 - March 31, 2023 - Development of novel protein-based therapeutics for lung cancer, Principal Investigator. Sponsor: NIH, Sponsor Award ID: R01CA225103

Education

Stanford University, B.S., 06/1989, Biology
Stanford University, B.A., 06/1989, Anthropology
University of California San Francisco, M.D., 06/1995, Medicine
University of California San Francisco, Residency, 06/1998, Pediatrics
Dana Farber Cancer Institute/Boston Children’s Hospital, Subspecialty training, 06/2002, Pediatric Hematology/Oncology

Honors & Awards

  • 1989
    Stanford University Firestone Award for Excellence in Undergraduate Research
  • 2006
    Sidney Kimmel Scholar Award
  • 2007
    Doris Duke Clinical Scientist Award
  • 2008
    Rita Allen Scholar Award
  • 2009
    Morgridge Scholar Award

Selected Publications

  1. Levinson A, Lee AG, Martell HJ, Breese MR, Zaloudek C, Van Ziffle J, Laguna B, Leung SG, Chen MD, Chen LM, Pfeil J, Ladwig NR, Shah AT, Behroozfard I, Rao AA, Salama SR, Sweet-Cordero EA, Stieglitz E Complete Response to PD-1 Inhibition in an Adolescent With Relapsed Clear Cell Adenocarcinoma of the Cervix Predicted by Neoepitope Burden and APOBEC Signature.  View on PubMed
  2. Kostyrko K, Sweet-Cordero EA An Expanded Tool Kit for Modeling the Oncogenic Functions of KRAS.  View on PubMed
  3. Hawkins C, Pfister S, Jones DTW, Shah NN, Gilbertson RJ, Sweet-Cordero EA, Dyer MA, Mossé YP, Haber M, DuBois SG Advances and Challenges in Pediatric and Childhood Cancers.  View on PubMed
  4. Broyde J, Simpson DR, Murray D, Paull EO, Chu BW, Tagore S, Jones SJ, Griffin AT, Giorgi FM, Lachmann A, Jackson P, Sweet-Cordero EA, Honig B, Califano A Oncoprotein-specific molecular interaction maps (SigMaps) for cancer network analyses.  View on PubMed
  5. Behnert A, Lee AG, Young EP, Breese MR, Leung SG, Behroozfard I, Maruffi M, Sweet-Cordero EA, Dvorak CC, Chu J, Stieglitz E NUP98-NSD1 Driven MDS/MPN in Childhood Masquerading as JMML.  View on PubMed
  6. Kelly MR, Kostyrko K, Han K, Mooney NA, Jeng EE, Spees K, Dinh PT, Abbott KL, Gwinn DM, Sweet-Cordero EA, Bassik MC, Jackson PK Combined Proteomic and Genetic Interaction Mapping Reveals New RAS Effector Pathways and Susceptibilities.  View on PubMed
  7. Kim JW, Marquez CP, Sperberg RAP, Wu J, Bae WG, Huang PS, Sweet-Cordero EA, Cochran JR Engineering a potent receptor superagonist or antagonist from a novel IL-6 family cytokine ligand.  View on PubMed
  8. Pfeil J, Sanders LM, Anastopoulos I, Lyle AG, Weinstein AS, Xue Y, Blair A, Beale HC, Lee A, Leung SG, Dinh PT, Shah AT, Breese MR, Devine WP, Bjork I, Salama SR, Sweet-Cordero EA, Haussler D, Vaske OM Hydra: A mixture modeling framework for subtyping pediatric cancer cohorts using multimodal gene expression signatures.  View on PubMed
  9. Valencia K, Erice O, Kostyrko K, Hausmann S, Guruceaga E, Tathireddy A, Flores NM, Sayles LC, Lee AG, Fragoso R, Sun TQ, Vallejo A, Roman M, Entrialgo-Cadierno R, Migueliz I, Razquin N, Fortes P, Lecanda F, Lu J, Ponz-Sarvise M, Chen CZ, Mazur PK, Sweet-Cordero EA, Vicent S The Mir181ab1 cluster promotes KRAS-driven oncogenesis and progression in lung and pancreas.  View on PubMed
  10. Han K, Pierce SE, Li A, Spees K, Anderson GR, Seoane JA, Lo YH, Dubreuil M, Olivas M, Kamber RA, Wainberg M, Kostyrko K, Kelly MR, Yousefi M, Simpkins SW, Yao D, Lee K, Kuo CJ, Jackson PK, Sweet-Cordero A, Kundaje A, Gentles AJ, Curtis C, Winslow MM, Bassik MC CRISPR screens in cancer spheroids identify 3D growth-specific vulnerabilities.  View on PubMed
  11. Schott C, Shah AT, Sweet-Cordero EA Genomic Complexity of Osteosarcoma and Its Implication for Preclinical and Clinical Targeted Therapies.  View on PubMed
  12. Kim JW, Marquez CP, Kostyrko K, Koehne AL, Marini K, Simpson DR, Lee AG, Leung SG, Sayles LC, Shrager J, Ferrer I, Paz-Ares L, Gephart MH, Vicent S, Cochran JR, Sweet-Cordero EA Antitumor activity of an engineered decoy receptor targeting CLCF1-CNTFR signaling in lung adenocarcinoma.  View on PubMed
  13. Sanders LM, Rangaswami A, Bjork I, Lam DL, Beale HC, Kephart ET, Durbin A, Learned K, Currie R, Lyle AG, Pfeil J, Shah AT, Lee AG, Leung SG, Behroozfard IH, Breese MR, Peralez J, Hazard FK, Lacayo N, Spunt SL, Haussler D, Salama SR, Sweet-Cordero EA, Vaske OM Comparative RNA-seq analysis aids in diagnosis of a rare pediatric tumor.  View on PubMed
  14. Fernandez KS, Turski ML, Shah AT, Bastian BC, Horvai A, Hardee S, Sweet-Cordero EA Ewing sarcoma in a child with neurofibromatosis type 1.  View on PubMed
  15. Vaske OM, Bjork I, Salama SR, Beale H, Tayi Shah A, Sanders L, Pfeil J, Lam DL, Learned K, Durbin A, Kephart ET, Currie R, Newton Y, Swatloski T, McColl D, Vivian J, Zhu J, Lee AG, Leung SG, Spillinger A, Liu HY, Liang WS, Byron SA, Berens ME, Resnick AC, Lacayo N, Spunt SL, Rangaswami A, Huynh V, Torno L, Plant A, Kirov I, Zabokrtsky KB, Rassekh SR, Deyell RJ, Laskin J, Marra MA, Sender LS, Mueller S, Sweet-Cordero EA, Goldstein TC, Haussler D Comparative Tumor RNA Sequencing Analysis for Difficult-to-Treat Pediatric and Young Adult Patients With Cancer.  View on PubMed
  16. Chao AK, Meyer JA, Lee AG, Hecht A, Tarver T, Van Ziffle J, Koegel AK, Golden C, Braun BS, Sweet-Cordero EA, Smith CC, Dvorak CC, Loh ML, Stieglitz E Fusion driven JMML: a novel CCDC88C-FLT3 fusion responsive to sorafenib identified by RNA sequencing.  View on PubMed
  17. Roberts RD, Lizardo MM, Reed DR, Hingorani P, Glover J, Allen-Rhoades W, Fan T, Khanna C, Sweet-Cordero EA, Cash T, Bishop MW, Hegde M, Sertil AR, Koelsche C, Mirabello L, Malkin D, Sorensen PH, Meltzer PS, Janeway KA, Gorlick R, Crompton BD Provocative questions in osteosarcoma basic and translational biology: A report from the Children's Oncology Group.  View on PubMed
  18. Ren Y, Huang S, Dai C, Xie D, Zheng L, Xie H, Zheng H, She Y, Zhou F, Wang Y, Li P, Fei K, Jiang G, Zhang Y, Su B, Sweet-Cordero EA, Tran NL, Yang Y, Patel JN, Rolfo C, Rocco G, Cardona AF, Tuzi A, Suter MB, Yang P, Xu W, Chen C Germline Predisposition and Copy Number Alteration in Pre-stage Lung Adenocarcinomas Presenting as Ground-Glass Nodules.  View on PubMed
  19. Sweet-Cordero EA, Biegel JA The genomic landscape of pediatric cancers: Implications for diagnosis and treatment.  View on PubMed
  20. Sayles LC, Breese MR, Koehne AL, Leung SG, Lee AG, Liu HY, Spillinger A, Shah AT, Tanasa B, Straessler K, Hazard FK, Spunt SL, Marina N, Kim GE, Cho SJ, Avedian RS, Mohler DG, Kim MO, DuBois SG, Hawkins DS, Sweet-Cordero EA Genome-Informed Targeted Therapy for Osteosarcoma.  View on PubMed

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