Alejandro Sweet-Cordero
Academic Appointments
- Associate Professor (Research), Pediatrics - Cancer Biology
- Member, Stanford Cancer Institute
- Member, Bio-X
- Member, Child Health Research Institute
Key Documents
Contact Information
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Clinical Offices
Pediatric Hematology-Oncology 725 Welch Rd MC 5798 Palo Alto, CA 94034 Tel Work (650) 497-8953 Fax (650) 497-8959Practices at Stanford Hospital and Clinics and Lucile Packard Children's Hospital
- Academic Offices
Personal Information EmailAlternate Contact Joel Schaefer Administrative Assistant Email Tel Work 49246Not for medical emergencies or patient use
Professional Overview
Clinical Focus
- Pediatric Hematology-Oncology
- Ewing's sarcoma
- Osteosarcoma
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)
Professional Education
| Fellowship: | Dana-Farber Cancer Institute MA (2002) |
| Internship: | UCSF Medical Center CA (1996) |
| Medical Education: | UCSF School of Medicine CA (1995) |
| B.A.: | Stanford University, Anthropology (1989) |
| B.S.: | Stanford University, Biology (1989) |
| MD: | UC San Francisco, Medicine (1995) |
Postdoctoral Advisees
Alexandra Abrams, Katherine Fuh, Dana Gwinn, Michelle Marques, Bethsaida Nieves, David Simpson
Graduate & Fellowship Program Affiliations
Internet Links
Scientific Focus
Current Research 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 use in clinical medicine, much is still unknown about the molecular and cellular determinants of chemotherapy response in cancer. We believe that important differences exist between how tumor cells in a plastic dish respond to therapy and how tumors in an organism respond to therapy. Therefore, 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. 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 in press).
Modeling solid tumor translocations in vivo and in vitro
Translocations are frequent genetic events in the genesis of many human cancers. They are particularly frequent in tumors common in pediatric patients (leukemias, sarcomas). We use gene targeting to produce mouse models in which translocation events can be activated temporally or in specific tissues. In particular, our laboratory is 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. A particular interest in the laboratory is the role of long non-coding RNAs in Ewing’s pathogenesis.
Publications
- Mathematical modeling of tumor cell proliferation kinetics and label retention in a mouse model of lung cancer. Cancer Res. 2013
- 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; (22): 5744-56
- Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer. Genes Dev. 2010; (8): 837-52
- Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models. J Clin Invest. 2010; (11): 3940-52
- The Phosphatase PP2A Links Glutamine to the Tumor Suppressor p53. Mol Cell. 2013; (2): 157-8
- Two Is Better Than One: Combining IGF1R and MEK Blockade as a Promising Novel Treatment Strategy Against KRAS-Mutant Lung Cancer. Cancer Discov. 2013; (5): 491-3
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