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The Carrasco Lab applies cutting-edge experimental and computational platforms to better understand, diagnose and treat human cancer and pre-cancerous conditions. With over two decades of experience in the field of pathology, oncology, hematology and molecular biology, our team develops and implements innovative methodologies to discover and characterize the fundamental drivers and vulnerabilities of cancer. The ultimate goal is to translate these discoveries into effective diagnostic and therapeutic strategies.
Carrasco Lab
Department of Pathology, Dana-Farber Cancer Institute
The Carrasco Lab investigates the role of genetic aberrations and associated signaling changes in cancer development and progression, with a focus on B-cell lymphoma (Waldenstrom's macroglobulinemia, DLBCL), colorectal cancer, gastric cancer, and multiple myeloma. Our research seeks to uncover the molecular mechanisms driving these malignancies at both premalignant and malignant stages, with the ultimate goal of developing rational, targeted therapies grounded in the principles of precision medicine.
Research highlights (click here to see more):
Research highlights (click here to see more):
The role and targeting of Wnt signaling in cancer
We have developed stabilized alpha-helix peptides of BCL9 that disrupt the β-catenin/BCL9 complex. These peptides selectively inhibit Wnt-driven transcription, suppress CRC and MM cell migration, and exhibit antitumor effects in both in vitro and in vivo models. This represents a novel pharmacological strategy for targeting oncogenic Wnt signaling. (image: Wang et al., Nature Communications, 2021)
We have developed stabilized alpha-helix peptides of BCL9 that disrupt the β-catenin/BCL9 complex. These peptides selectively inhibit Wnt-driven transcription, suppress CRC and MM cell migration, and exhibit antitumor effects in both in vitro and in vivo models. This represents a novel pharmacological strategy for targeting oncogenic Wnt signaling. (image: Wang et al., Nature Communications, 2021)
The role of 6q deletion in lymphoma
We have developed mouse models with Cre-inducible deletion of the minimal consensus region corresponding to 6q deletion commonly observed in blood and solid cancers. These models allow the targeted deletion of a 30.5 Mb region on syntenic murine chromosome 10q, resulting in the loss of 162 syntenic genes. We are interested in the early and late cellular consequences induced by 6q deletion. Our studies of lymphoma development in mice allow us to discover early lymphoma precursors, describe the events leading to oncogenic transformation, and search for therapeutic targets. Ultimately, our mouse models are ideal for testing new anti-lymphoma drugs before initiating clinical trials.
We have developed mouse models with Cre-inducible deletion of the minimal consensus region corresponding to 6q deletion commonly observed in blood and solid cancers. These models allow the targeted deletion of a 30.5 Mb region on syntenic murine chromosome 10q, resulting in the loss of 162 syntenic genes. We are interested in the early and late cellular consequences induced by 6q deletion. Our studies of lymphoma development in mice allow us to discover early lymphoma precursors, describe the events leading to oncogenic transformation, and search for therapeutic targets. Ultimately, our mouse models are ideal for testing new anti-lymphoma drugs before initiating clinical trials.
Discovery of new β-catenin/BCL9 PPI inhibitors
We are actively refining our β-catenin/BCL9 protein-protein interaction small-molecule inhibitors through collaboration with Jun Qi's medicinal chemistry team, aiming to develop compounds with improved pharmacokinetics and pharmacodynamics for enhanced therapeutic potential.
We are actively refining our β-catenin/BCL9 protein-protein interaction small-molecule inhibitors through collaboration with Jun Qi's medicinal chemistry team, aiming to develop compounds with improved pharmacokinetics and pharmacodynamics for enhanced therapeutic potential.
Preclinical murine models
Our lab has established mouse xenograft models for CRC and MM to study tumor progression, metastasis, and test novel Wnt inhibitors. These models provide invaluable insights into the cellular and molecular mechanisms of cancer pathogenesis.
Our lab has established mouse xenograft models for CRC and MM to study tumor progression, metastasis, and test novel Wnt inhibitors. These models provide invaluable insights into the cellular and molecular mechanisms of cancer pathogenesis.
- We have also generated transgenic mice that spontaneously develop B-cell acute lymphoblastic leukemia, as well as lung and gastric carcinomas. These models serve as robust platforms for testing the efficacy and specificity of small-molecule inhibitors targeting the β-catenin/BCL9 interaction. (image: Sewastianik, Guerrera et al., Blood Advances, 2019).
Featured publications (click here to see more):
A novel β-catenin/BCL9 complex inhibitor blocks oncogenic Wnt signaling and disrupts cholesterol homeostasis in colorectal cancer
Tanton, Sewastianik et al., Science Advances, 2021
Dysregulated Wnt/β-catenin signaling drives many cancers, including colorectal cancer (CRC). To target this pathway, we developed a high-throughput AlphaScreen assay to identify small-molecule inhibitors of the β-catenin/BCL9 interaction. We discovered a compound that binds β-catenin, disrupts its complex with BCL9, inhibits Wnt signaling, alters cholesterol homeostasis, and suppresses CRC cell proliferation and tumor growth in a xenograft model. This inhibitor offers a valuable tool for studying Wnt signaling and holds promise for developing new CRC therapies. Read more
Tanton, Sewastianik et al., Science Advances, 2021
Dysregulated Wnt/β-catenin signaling drives many cancers, including colorectal cancer (CRC). To target this pathway, we developed a high-throughput AlphaScreen assay to identify small-molecule inhibitors of the β-catenin/BCL9 interaction. We discovered a compound that binds β-catenin, disrupts its complex with BCL9, inhibits Wnt signaling, alters cholesterol homeostasis, and suppresses CRC cell proliferation and tumor growth in a xenograft model. This inhibitor offers a valuable tool for studying Wnt signaling and holds promise for developing new CRC therapies. Read more
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