We have developed several novel approaches for analysis of massively parallel gene expression datasets. First, StepMiner, a tool that identi?es step-wise transitions in the time course microarray datasets. Second, BooleanNet, a method of discovering Boolean implications between genes using these large numbers of gene expression datasets. Recently, we published a new method called MiDReG (Mining Developmentally Regulated Genes) that uses Boolean implications to successfully predict genes in developmental pathways. By initially applying this approach to lymphocyte differentitaion, we discovered previously unrecognized markers for B cell differentiation, as well as a novel branchpoint of B cell and T cell development. The proposed project will build on our successful prediction of human B cell developmental genes using MiDReG to develop a general method for discovering cancer stem and progenitor cells. I am planning to validate this approach in human bladder cancer (Transitional Cell Carcinoma), ?rst, because it is a simple model cancer to test, and, second, because our laboratory has the expertise to isolate and test cell populations for tumor-initiating potential. This method will be optimized for the discovery of stem and progenitor cells in bladder cancer and hopefully it will serve as a starting point for similar studies in other types of cancers. More than 90% of human bladder cancers arise from a simple epithelial tissue called urothelium, and are commonly called transitional cell carcinomas (TCC). Furthermore, human bladder cancer is ?fth most common cancer in the United States. Our laboratory has established a working model for the xenotransplantation of human bladder cancer in mice and has recently discovered a tumor-initiating population in bladder cancer. Recent studies show that cancer is heterogeneous and forms a hierarchy of original tumor cell populations. However, a detailed bladder cancer developmental hierarchy remains unknown. My primary near-term goal in this proposal is to understand this hierarchy of bladder cancer cells using a systems biology approach to predict (diagnostic/prognostic) genes that mark speci?c populations. I will validate this approach using human cancer tissue microarrays in collaboration with Dr. Matt van de Rijn ,and using xenotransplantation in collaboration with Drs. Robert Chin and Jens-Peter Volkmer. In the longer term, I will extend the method to identify stem and progenitor cells in other types of cancers during my independent investigator phase.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Transition Award (R00)
Project #
Application #
Study Section
No Study Section (in-house review) (NSS)
Program Officer
Li, Jerry
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
Schools of Medicine
La Jolla
United States
Zip Code
Sereti, Konstantina-Ioanna; Nguyen, Ngoc B; Kamran, Paniz et al. (2018) Analysis of cardiomyocyte clonal expansion during mouse heart development and injury. Nat Commun 9:754
Sahoo, Debashis; Wei, Wei; Auman, Heidi et al. (2018) Boolean analysis identifies CD38 as a biomarker of aggressive localized prostate cancer. Oncotarget 9:6550-6561
Kahn, Suzana A; Wang, Xin; Nitta, Ryan T et al. (2018) Notch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma. Nat Commun 9:4121
Cai, Shang; Kalisky, Tomer; Sahoo, Debashis et al. (2017) A Quiescent Bcl11b High Stem Cell Population Is Required for Maintenance of the Mammary Gland. Cell Stem Cell 20:247-260.e5
Sin, Mandy L Y; Mach, Kathleen E; Sinha, Rahul et al. (2017) Deep Sequencing of Urinary RNAs for Bladder Cancer Molecular Diagnostics. Clin Cancer Res 23:3700-3710
Medal, Rachel M; Im, Amanda M; Yamamoto, Yasutoshi et al. (2017) The innate immune response in fetal lung mesenchymal cells targets VEGFR2 expression and activity. Am J Physiol Lung Cell Mol Physiol 312:L861-L872
Dalerba, Piero; Sahoo, Debashis; Paik, Soonmyung et al. (2016) CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer. N Engl J Med 374:211-22
Skelton, Rhys J P; Brady, Bevin; Khoja, Suhail et al. (2016) CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells. Stem Cell Reports 6:95-108
Krampitz, Geoffrey Wayne; George, Benson M; Willingham, Stephen B et al. (2016) Identification of tumorigenic cells and therapeutic targets in pancreatic neuroendocrine tumors. Proc Natl Acad Sci U S A 113:4464-9
Dalerba, Piero; Sahoo, Debashis; Clarke, Michael F (2016) CDX2 as a Prognostic Biomarker in Colon Cancer. N Engl J Med 374:2184

Showing the most recent 10 out of 20 publications