E. Alejandro Sweet-Cordero, MD

Associate Professor
Department of Pediatrics
Benioff Chair of Child Health
Division of Hematology and Oncology
+1 415 476-7781

The goal of my laboratory 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 understand how cancers become resistant to chemotherapy. We have two primary disease interests: lung cancer and pediatric sarcomas. 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). In our sarcoma work, we are interested in mechanisms driving osteosarcoma and Ewing sarcoma progression. We recently identified the first lncRNA involved in the pathogenesis of Ewing sarcoma (Howarth et al, JCI, 2014). We rely heavily on computational genomic analysis in our work and we have extensive experience in generating and using high-throughput datasets and next-generation sequencing for gene and network discovery. We are also 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.

Primary Thematic Area: 
Cancer Biology & Cell Signaling
Secondary Thematic Area: 
Developmental & Stem Cell Biology
Research Summary: 
We use genetics and functional genomics to study cancer biology in mouse and human systems. Current emphasis is on lung cancer and pediatric sarcomas.

Websites

Publications: 

An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency.

Cancer cell

Brady JJ, Chuang CH, Greenside PG, Rogers ZN, Murray CW, Caswell DR, Hartmann U, Connolly AJ, Sweet-Cordero EA, Kundaje A, Winslow MM

Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma.

Nature medicine

Mazur PK, Herner A, Mello SS, Wirth M, Hausmann S, Sánchez-Rivera FJ, Lofgren SM, Kuschma T, Hahn SA, Vangala D, Trajkovic-Arsic M, Gupta A, Heid I, Noël PB, Braren R, Erkan M, Kleeff J, Sipos B, Sayles LC, Heikenwalder M, Heßmann E, Ellenrieder V, Esposito I, Jacks T, Bradner JE, Khatri P, Sweet-Cordero EA, Attardi LD, Schmid RM, Schneider G, Sage J, Siveke JT

Long noncoding RNA EWSAT1-mediated gene repression facilitates Ewing sarcoma oncogenesis.

The Journal of clinical investigation

Marques Howarth M, Simpson D, Ngok SP, Nieves B, Chen R, Siprashvili Z, Vaka D, Breese MR, Crompton BD, Alexe G, Hawkins DS, Jacobson D, Brunner AL, West R, Mora J, Stegmaier K, Khavari P, Sweet-Cordero EA

A meta-analysis of lung cancer gene expression identifies PTK7 as a survival gene in lung adenocarcinoma.

Cancer research

Chen R, Khatri P, Mazur PK, Polin M, Zheng Y, Vaka D, Hoang CD, Shrager J, Xu Y, Vicent S, Butte AJ, Sweet-Cordero EA

A rare population of CD24(+)ITGB4(+)Notch(hi) cells drives tumor propagation in NSCLC and requires Notch3 for self-renewal.

Cancer cell

Zheng Y, de la Cruz CC, Sayles LC, Alleyne-Chin C, Vaka D, Knaak TD, Bigos M, Xu Y, Hoang CD, Shrager JB, Fehling HJ, French D, Forrest W, Jiang Z, Carano RA, Barck KH, Jackson EL, Sweet-Cordero EA