Cancer Systems Biology Consortium (CSBC)

Transcription

1 Cancer Systems Biology Consortium (CSBC) Shannon Hughes, Ph.D. Program Director, Tumor Metastasis Branch Division of Cancer Biology, NCI ITCR PI Teleconference; February 2, 2018

2 Systems Biology at NCI 10 years of the Integrative Cancer Biology Program (ICBP) program evaluation New Initiative - Cancer Systems Biology Consortium (CSBC) Approved March 2015 Three funding announcements issued: Research Centers (), Research Projects (), and Coordinating Center (U24) NCI Program Staff: Erin Wetzel, Dave Miller, Nas Zahir, Shannon Hughes, Jerry Li, Jennifer Couch, Dan Gallahan, Dinah Singer 2

3 Structure of the Cancer Systems Biology Consortium Initiative Coordinating Center U24 Research Center Research Project CSBC Steering Committee Collaborative Projects Working Groups Annual Meetings Outreach (Summer Program) CSBC s: PAR (next receipt date June 22, 2018) CSBC s: RFA-CA (closed) CSBC U24: RFA-CA (closed) 3

4 Current CSBC Portfolio 9 CSBC Research Centers (as of 5/1/17) 1 U24 CSBC/PS-ON Coordinating Center 14 Research Projects 8 Active Collaborative Research in Integrative Cancer Biology (PAR ) 6 CSBC Research Projects (PAR ) Also 5 Active Bridging the Gap Between Cancer Mechanism and Population Science Information on currently funded projects can be found at *** 4

5 Current CSBC / Award Portfolio (23 awards) Categories: Research Theme (2 Major/Minor) Experimental Approaches (2) Computational Approaches (2) For example: Research Theme 1. Tumor Heterogeneity 2. Metastasis 3. Cancer Therapeutics 4. Microenvironment 5. Tumor Immunology 6. Dormancy Research Theme Each Project/Center represented by 6 element vector Ex. MSKCC [ ] Experimental Approach Computational Approach Pairwise Hamming Distance calculated between grants 5

6 Current CSBC / Award Portfolio Edges are weights calculated from Hamming Distance Thicker/Darker line = high similarity Grouped by Research Theme Tumor Heterogeneity Metastasis Cancer Therapeutics Tumor Immune/Stroma Dormancy 6

7 Current CSBC / Award Portfolio Edges are weights calculated from Hamming Distance Thicker line = high similarity Grouped by Research Theme Colored by Experimental Method Genomics/Transcriptomics Proteomics/PPI Imaging Epigenetics Single-Cell Analysis Metabolomics 7

8 Current CSBC / Award Portfolio Edges are weights calculated from Hamming Distance Thicker line = high similarity Grouped by Research Theme Colored by Computational Approach ML/DL Approaches Network Inference/Statistical Ecological/Evolutionary Mechanistic (ODE, etc) 8

9 Example: Combating subclonal evolution of resistant cancer phenotypes Track tumor evolution to determine appropriate treatment options Modified from Brady et al. Nature Comm, Nov Andrea Bild City of Hope CSBC 9

10 Example: Combating subclonal evolution of resistant cancer phenotypes 1) Combination of bulk WGS, WES and targeted single-cell DNA Seq to determine what mutations (subclones) are present in the tumor Dot = mutation Collection of dots = subclone 2) Over time, use single-cell RNASeq to determine which pathways are active in particular clones Modified from Brady et al. Nature Comm, Nov Andrea Bild City of Hope CSBC 10

11 PanCK CD3 CD4 CD8 FoxP3 Non-small cell lung cancer (NSCLC) Slide courtesy of Vivek Mittal Weill Cornell, CSBC

12 Identify key components Stromal cells (Paracrine) or Tumor cells (Autocrine) Differentially upregulated Ligands Expressed Receptors Tumor cells Expressed Transcription Factors/Differentially Expressed Target genes CCCExplorer Algorithm for Crosstalk Signaling Discovery paracrine Ligand-Receptor interactions Downstream signaling pathways G(V,E): signaling pathway V L : up-regulated ligand list V R : expressed receptor list V TF : activated TF list V T :up-regulated target gene list Distance Matrix Combine activated signaling branches autocrine Identify activated signaling pathways as a directed graph V L V R V i Distance 0 Distance 1 Distance 2 V j V TF V T Activated signaling branches (p<0.05) wwww.synapse.org/ CSBCPSON Slide modified from Stephen Wong Methodist Hospital CSBC

13 Ash Alizadeh Stanford CSBC 13

14 Using systems biology to probe tumor-immune interactions and mechanisms of immunotherapy 14

15 Knowledge Portal: gateway to CSBC/PS-ON activities Knowledge Portal Website

16 Building the CSBC/PS-ON Knowledge Portal Exposes and provides access to research activities and resources across Centers and Projects Serves as central gateway for scientific community to discover and utilize consortium material Community CSBC/PS-ON Knowledge Portal R O U24 C Slide care of Justin Guinney, Sage Bionetworks: CSBC/PS-ON Coordinating Center

17 CSBC/PS-ON Summer Undergraduate Research Program Applications are due February 16,

18 November 7-10, 2018 Woods Hole, MA Organized by AECCSB & NCI Scientific Co-chairs: Sylvia Plevritis, Stanford University Sandy Anderson, Moffitt Cancer Center Doug Lauffenburger, MIT See speaker line-up: Travel support will be available for select abstracts. for updates 18

19 Association of Early Career Cancer Systems Biologists (AECCSB) Purpose: Build a cancer systems biology community starting from scientists trained as part of the Integrative Cancer Biology Program. Help ESIs grow a network of like-minded scientists and promote advances by young investigators in the field (aameyer@ucla.edu) (stephen.piccolo.byu@gmail.com)

20 @NCISysBio