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Alejandro Sweet-Cordero

Academic Appointments

  • Associate Professor (Research) of Pediatrics (Cancer Biology)

Key Documents

Contact Information

  • Clinical Offices
    Pediatric Hematology-Oncology LLSCRB 2078B MC 5457 Stanford, CA 94305
    Tel Work (650) 725-5901 Fax (650) 725-5903
  • Academic Offices
    Personal Information
    Email
    Administrative Assistant
    Alyssa Ray Duran Administrative Assistant Tel Work 49246
    Not for medical emergencies or patient use

Bio

I completed by undergraduate studies at Stanford (BA-Anthropology, BS-Biology)., followed by medical school and pediatric residency at UCSF. I then completed clinical training in pediatric oncology at the Dana Farber Cancer Institute and Boston Children's Hospital, followed by a research post-doctoral fellowship under the mentorship of Tyler Jacks at MIT. I have been on the Stanford faculty since 2005. I run a research lab focused on cancer biology with disease interests in pediatric sarcomas and lung cancer. I am a physician-scientist and I attend on the oncology service at Packard Children's Hospital.

Clinical Focus

  • Pediatric Hematology-Oncology
  • clinical genomics
  • pediatric sarcomas

Academic Appointments

Honors and Awards

  • Innovative Research Award, SU2C (6/2011-6/2014)
  • member, American Society for Clinical Investigation (2010)
  • Scholar Award, Rita Allen Foundation (2008-2011)
  • Clinical Scientist Development Award, Doris Duke Foundation (2007-2010)
  • Sidney Kimmel Scholar, Sidney Kimmel Foundation (2006-2008)

Boards, Advisory Committees, Professional Organizations

  • Member, American Association for Cancer Research (2006 - present)

Professional Education

Residency: Univ of California San Francisco CA (1998)
Internship: Univ of California San Francisco CA (1996)
Fellowship: Dana-Farber Cancer Institute MA (2002)
Medical Education: UCSF School of Medicine CA (1995)
B.A.: Stanford University, Anthropology (1989)
B.S.: Stanford University, Biology (1989)
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Research & Scholarship

Current Research and Scholarly Interests

The long-term goal of our laboratory is to identify novel targets for cancer therapy in order to improve the lives of cancer patients. We use genome-wide analysis tools (RNAseq, WGS, microarrays etc) to understand the consequences of oncogenic mutations at a system-wide level. We have found that comparing genome-wide changes in mouse models of cancer with those seen in primary human tumors is a fruitful approach for the discovery of novel genes and pathways important in oncogenesis. We continue to exploit such cross species comparisons as a tool for understanding cancer pathways and networks. We also use shRNA technology both in vitro and in vivo to perform functional studies of genes identified in our genomic screens. Our laboratory has a genome-wide lentiviral shRNA library available which greatly facilitates these studies.

Specific Projects Include:

Kras signaling.

Kras is one of the most frequently mutated genes in human cancer. Many signaling pathways have been described as being necessary for Kras induced oncogenic transformation. However, the specific pathways required are strongly dependent on the tissue origin (fibroblast vs epithelial cell) and the species of the model system used. Using cross-species microarray analysis, we have uncovered a gene expression profile associated with Kras mutation across species and in different tissues (Sweet-Cordero, Nature Genetics 2005). We have used shRNA- based screens to study the functional significance of this signature. For example, we identified Wt1 as a key regulator of the Kras signature and also a gene whose loss leads to “synthetic senescence” in the context of oncogenic Kras activation (Vicent et al, JCI, 2010). Current studies are focused on identifying novel critical regulators of Kras function, primarily in lung cancer.

Chemotherapy response in vivo

Despite decades of clinical use, much is still unknown about the molecular and cellular determinants of chemotherapy response in cancer. We rely on mouse models that closely recapitulate important aspects of human oncogenesis to study chemotherapy response (Oliver et al Genes and Development, 2010). We are particularly interested in uncovering why tumor-propagating cells (TPCs, also called cancer stem cells) are chemoresistant. Recently, we described and characterized a tumor-propagating population of cells that is dependent on Notch3 signaling (Zheng et al Cancer Cell 2013). Other work is focused on determining how the tumor microenvironment contributes to tumor growth (Vicent et al, Cancer Research 2012) and understanding the kinetics of TPCs in vivo (Zheng et al, Cancer Research 2013).

Modeling solid tumor translocations in vivo and in vitro

Translocations are genetic events present in many cancer types. They are particularly frequent in tumors common in pediatric patients. We use gene targeting to produce mouse models in which translocation events can be activated temporally or in specific tissues. We are using gene targeting approaches in the mouse to study the oncogenesis mediated by fusion of the gene EWS with ets family transcription factors such as Fli-1 and Erg. Such translocations are seen in Ewing’s Sarcoma, a bone tumor found mostly in children. Using human mesenchymal stem cells, we are also exploring what genetic events other than oncogenic translocation are required for tumor initiation and progression. Recently we described a role for a long non-coding RNA (lncRNA) in the pathogenesis of Ewing sarcoma (Howarth et al Journal of Clinical Investigation, 2014).

Personalized Approaches to Pediatric Oncology

Our lab is leading an effort in the division of pediatric oncology at Packard Children’s hospital to develop more focused, genomics-based approaches to the care of patients with solid tumors. This effort focuses on using WGS, RNAseq and other genomic technologies to identify novel theapies for patients with metastatic or relapsed cancer.

Clinical Trials

Teaching

Courses

2014-15

Postdoctoral Advisees

Dana GwinnAmanda KoehneSiu Ping NgokDavid Simpson

Graduate and Fellowship Program Affiliations

Publications

Publications

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Publication Topics

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