The Sweet-Cordero Laboratory
Our goal is to identify novel therapeutic approaches for cancer by targeting mutations and altered signaling networks.
Our Research
We have two primary disease interests: lung cancer and pediatric sarcomas.  

Welcome to the Sweet-Cordero Labratory

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 lung cancer, our laboratory has identified novel regulators of chemoresistance in lung cancer (Oliver et al, 2010 Genes and Development). We have used functional genomics in mouse and human models to identify a novel role for Wt1 in mediating KRAS-driven oncogenesis (Vicent et al, 2010, JCI). We have identified and characterized the role of tumor-propagating cells in NSCLC and identified a key role for Notch3 as a self-renewal pathway in mouse and human NSCLC (Zheng et al, 2013, 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).  Our lab uses both genetically engineered and patient-derived xenograft models to study lung cancer.

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.  We have established a large panel of sarcoma PDX models (over 15 OS models, 5 EWS models, 4 RMS models and several other models for rare sarcomas). We are using these models to explore the genomic evolution of sarcomas and define novel therapeutics that are informed by the genomic alterations present in individual tumors.

We make extensive use of computational genomic approaches in our work and we have extensive experience in generating and using next-generation sequencing 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 100 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.

Alejandro Sweet-Cordero is a member of the following graduate programs at UCSF: