1. A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.

    Cell 162(1):146 (2015) PMID 26140595

    KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell...
  2. Leukemia-Associated Somatic Mutations Drive Distinct Patterns of Age-Related Clonal Hemopoiesis

    Cell Reports 10(8):1239 (2015) PMID 25732814

    Clonal hemopoiesis driven by leukemia-associated gene mutations can occur without evidence of a blood disorder. To investigate this phenomenon, we interrogated 15 mutation hot spots in blood DNA from 4,219 individuals using ultra-deep sequencing. Using only the hot spots studied, we id...
  3. Leukemia-Associated Somatic Mutations Drive Distinct Patterns of Age-Related Clonal Hemopoiesis

    Cell Reports 10(8):1239 (2015) PMID 25732814

    Clonal hemopoiesis driven by leukemia-associated gene mutations can occur without evidence of a blood disorder. To investigate this phenomenon, we interrogated 15 mutation hot spots in blood DNA from 4,219 individuals using ultra-deep sequencing. Using only the hot spots studied, we id...
  4. A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer.

    Nature Genetics 47(1):47 (2015) PMID 25485836

    Here we describe a conditional piggyBac transposition system in mice and report the discovery of large sets of new cancer genes through a pancreatic insertional mutagenesis screen. We identify Foxp1 as an oncogenic transcription factor that drives pancreatic cancer invasion and spread in a mouse...
  5. A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer.

    Nature Genetics 47(1):47 (2015) PMID 25485836

    Here we describe a conditional piggyBac transposition system in mice and report the discovery of large sets of new cancer genes through a pancreatic insertional mutagenesis screen. We identify Foxp1 as an oncogenic transcription factor that drives pancreatic cancer invasion and spread in a mouse...
  6. Disruption of the PRKCD-FBXO25-HAX-1 axis attenuates the apoptotic response and drives lymphomagenesis.

    Nature Medicine 20(12):1401 (2014) PMID 25419709

    We searched for genetic alterations in human B cell lymphoma that affect the ubiquitin-proteasome system. This approach identified FBXO25 within a minimal common region of frequent deletion in mantle cell lymphoma (MCL). FBXO25 encodes an orphan F-box protein that determines the substrate specif...
  7. Disruption of the PRKCD-FBXO25-HAX-1 axis attenuates the apoptotic response and drives lymphomagenesis.

    Nature Medicine 20(12):1401 (2014) PMID 25419709

    We searched for genetic alterations in human B cell lymphoma that affect the ubiquitin-proteasome system. This approach identified FBXO25 within a minimal common region of frequent deletion in mantle cell lymphoma (MCL). FBXO25 encodes an orphan F-box protein that determines the substrate specif...
  8. Disruption of the PRKCD-FBXO25-HAX-1 axis attenuates the apoptotic response and drives lymphomagenesis.

    Nature Medicine 20(12):1401 (2014) PMID 25419709

    We searched for genetic alterations in human B cell lymphoma that affect the ubiquitin-proteasome system. This approach identified FBXO25 within a minimal common region of frequent deletion in mantle cell lymphoma (MCL). FBXO25 encodes an orphan F-box protein that determines the substrate specif...
  9. Disruption of the PRKCD-FBXO25-HAX-1 axis attenuates the apoptotic response and drives lymphomagenesis.

    Nature Medicine 20(12):1401 (2014) PMID 25419709

    We searched for genetic alterations in human B cell lymphoma that affect the ubiquitin-proteasome system. This approach identified FBXO25 within a minimal common region of frequent deletion in mantle cell lymphoma (MCL). FBXO25 encodes an orphan F-box protein that determines the substrate specif...
  10. A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer.

    Nature Medicine 20(11):1340 (2014) PMID 25326799 PMCID PMC4270133

    Genetically engineered mouse models (GEMMs) have dramatically improved our understanding of tumor evolution and therapeutic resistance. However, sequential genetic manipulation of gene expression and targeting of the host is almost impossible using conventional Cre-loxP-based models. We have dev...
  11. A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer.

    Nature Medicine 20(11):1340 (2014) PMID 25326799 PMCID PMC4270133

    Genetically engineered mouse models (GEMMs) have dramatically improved our understanding of tumor evolution and therapeutic resistance. However, sequential genetic manipulation of gene expression and targeting of the host is almost impossible using conventional Cre-loxP-based models. We have dev...
  12. Chromatin landscapes of retroviral and transposon integration profiles.

    PLoS Genetics 10(4):e1004250 (2014) PMID 24721906 PMCID PMC3983033

    The ability of retroviruses and transposons to insert their genetic material into host DNA makes them widely used tools in molecular biology, cancer research and gene therapy. However, these systems have biases that may strongly affect research outcomes. To address this issue, we generated very ...
  13. Chromatin landscapes of retroviral and transposon integration profiles.

    PLoS Genetics 10(4):e1004250 (2014) PMID 24721906 PMCID PMC3983033

    The ability of retroviruses and transposons to insert their genetic material into host DNA makes them widely used tools in molecular biology, cancer research and gene therapy. However, these systems have biases that may strongly affect research outcomes. To address this issue, we generated very ...
  14. Tumor imaging and targeting potential of an Hsp70-derived 14-mer peptide.

    PLoS ONE 9(8):e105344 (2014) PMID 25165986 PMCID PMC4148261

    We have previously used a unique mouse monoclonal antibody cmHsp70.1 to demonstrate the selective presence of a membrane-bound form of Hsp70 (memHsp70) on a variety of leukemia cells and on single cell suspensions derived from solid tumors of different entities, but not on non-transformed cells ...
  15. Tumor imaging and targeting potential of an Hsp70-derived 14-mer peptide.

    PLoS ONE 9(8):e105344 (2014) PMID 25165986 PMCID PMC4148261

    We have previously used a unique mouse monoclonal antibody cmHsp70.1 to demonstrate the selective presence of a membrane-bound form of Hsp70 (memHsp70) on a variety of leukemia cells and on single cell suspensions derived from solid tumors of different entities, but not on non-transformed cells ...
  16. A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention.

    Cancer Cell 24(1):15 (2013) PMID 23845441 PMCID PMC3706745

    We show that BRAF(V600E) initiates an alternative pathway to colorectal cancer (CRC), which progresses through a hyperplasia/adenoma/carcinoma sequence. This pathway underlies significant subsets of CRCs with distinctive pathomorphologic/genetic/epidemiologic/clinical characteristics. Genetic an...
  17. A Genetic Progression Model of BrafV600E-Induced Intestinal Tumorigenesis Reveals Targets for Therapeutic Intervention

    Cancer Cell 24(1):15 (2013)

    We show that BRAFV600E initiates an alternative pathway to colorectal cancer (CRC), which progresses through a hyperplasia/adenoma/carcinoma sequence. This pathway underlies significant subsets of CRCs with distinctive pathomorphologic/genetic/epidemiologic/clinical characteristics. Ge...
  18. Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer.

    Cancer Cell 23(3):406 (2013) PMID 23453624

    Oncogenic Kras activates a plethora of signaling pathways, but our understanding of critical Ras effectors is still very limited. We show that cell-autonomous phosphoinositide 3-kinase (PI3K) and 3-phosphoinositide-dependent protein kinase 1 (PDK1), but not Craf, are key effectors of oncogenic K...
  19. Selective Requirement of PI3K/PDK1 Signaling for Kras Oncogene-Driven Pancreatic Cell Plasticity and Cancer

    Cancer Cell 23(3):406 (2013)

    Oncogenic Kras activates a plethora of signaling pathways, but our understanding of critical Ras effectors is still very limited. We show that cell-autonomous phosphoinositide 3-kinase (PI3K) and 3-phosphoinositide-dependent protein kinase 1 (PDK1), but not Craf, are key effectors of o...
  20. Selective Requirement of PI3K/PDK1 Signaling for Kras Oncogene-Driven Pancreatic Cell Plasticity and Cancer

    Cancer Cell 23(3):406 (2013) PMID 23453624

    Oncogenic Kras activates a plethora of signaling pathways, but our understanding of critical Ras effectors is still very limited. We show that cell-autonomous phosphoinositide 3-kinase (PI3K) and 3-phosphoinositide-dependent protein kinase 1 (PDK1), but not Craf, are key effectors of o...