Alejandro Sweet-Cordero

Clinical Focus

• Pediatric Hematology-Oncology

Honors and Awards

• 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

Postdoctoral Advisees

Diego Jaitin , Shuang Niu , Yanyan Zheng

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Pediatrics

Web Site Links

• Sweet-Cordero Laboratory

Research Interests

Our laboratory is devoted to the analysis of pathways involved in the initiation, progression, and maintenance of cancer. Utilizing the mouse as a model system, we strive to understand aberrant oncogenic signaling, the role of the tumor microenvironment and the mechanisms involved in chemotherapy response and resistance at the molecular, cellular, and organismal levels.

We use genome-wide analysis tools (microarrays, proteomics, etc) to understand the consequences of oncogenic mutations at a system-wide level. We have found that comparing genome-wide changes in a model system 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 rely heavily on shRNA technology both in vitro and in vivo to perform functional studies of genes identified in our genomic screens.

Specific Projects Include:

Kras signaling.

Kras is one of the most frequently mutated genes in human cancer. Many signaling pathways (MAPK, AKT, RALGDS) 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. We are using shRNA- based screens to study the functional significance of this signature. We are using this gene expression signature to understand how aberrant Kras signaling relays information to transcription factors that ultimately lead to changes in gene expression. Using a combination of biochemical, cell-based and in vivo studies, we are identifying novel genes involved in Kras induced oncogenesis and characterizing...

Publications

• Comparison of gene expression and DNA copy number changes in a murine model of lung cancer. Sweet-Cordero A, Tseng GC, You H, Douglass M, Huey B, Albertson D, Jacks T. Genes Chromosomes Cancer. 2006; 45 (4): 338-48
• An oncogenic KRAS2 expression signature identified by cross-species gene-expression analysis. Sweet-Cordero A, Mukherjee S, Subramanian A, You H, Roix JJ, Ladd-Acosta C, Mesirov J, Golub TR, Jacks T. Nat Genet. 2005; 37 (1): 48-55
• Requirement for Rac1 in a K-ras induced lung cancer in the mouse. Kissil JL, Walmsley MJ, Hanlon L, Haigis KM, Bender Kim CF, Sweet-Cordero A, Eckman MS, Tuveson DA, Capobianco AJ, Tybulewicz VL, Jacks T. Cancer Res. 2007; 67 (17): 8089-94
• Mouse models of human non-small-cell lung cancer: raising the bar. Kim CF, Jackson EL, Kirsch DG, Grimm J, Shaw AT, Lane K, Kissil J, Olive KP, Sweet-Cordero A, Weissleder R, Jacks T. Cold Spring Harb Symp Quant Biol. 2005: 70 241-50
• MicroRNA expression profiles classify human cancers. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. Nature. 2005; 435 (7043): 834-8