Ruben Carrasco, MD, PhD

Ruben Carrasco, MD, PhD

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Ruben Carrasco, MD, PhD

Dr. Carrasco received his MD in 1991 from the University of Chile School of Medicine. He trained in surgical pathology and hematopathology at Massachusetts General Hospital and Brigham and Women's Hospital; he is board-certified in both fields. In 2001, he worked in the laboratory of Dr. Ronald DePinho as a postdoctoral research fellow. After completing this training, Dr. Carrasco joined the faculty in 2004. He has a long-standing interest in hematological malignancies and is currently investigating the genetic events leading to disease pathogenesis in multiple myeloma.



Associate Professor of Pathology, Harvard Medical School


Board Certification

  • Anatomic Pathology, 2001
  • Hematology, 2001


  • Barros Lucos Trudeau, Pathology
  • Massachusetts General Hospital, Pathology

Medical School

  • Universidad De Chile

Recent Awards

  • Kimmel Award 2005


    Oncogenomic Studies and Disease Pathogenesis of Multiple Myeloma

    Multiple myeloma (MM), a multifocal plasma cell neoplasm, remains incurable despite conventional high-dose chemotherapy. The development of rational-based therapeutics for MM requires a detailed knowledge of the mutations driving this malignancy. It stands to reason that a more complete view of these genetic lesions would increase opportunities for cancer drug development. It is equally imperative that biological systems be developed to better validate these target genes. Genomic studies Our laboratory is working to identify the genetic events leading to MM. To this end, we have developed a thorough molecular profile of MM pathogenesis by analyzing cancer-associated alterations in the DNA and RNA of clinically annotated specimens and established cell lines. This oncogenomic analysis has yielded genetic elements of MM with strong biological and clinical correlates to other tumor types, to survival, and to known oncogenes and tumor suppressor genes, or their homologues, not previously implicated in MM pathogenesis. Biological systems - our next challenge is to identify which genes within newly identified loci are myeloma oncogenes or tumor suppressor genes, and to understand the role that these genes play in the genesis and progression of MM. To characterize these genes, we are conducting functional studies that include in vitro cell-based assays as well as hematopoietic stem cell transplantation and genetically engineered mice. Biologic correlates - in conjunction with the Pathology Department at Brigham and Women's Hospital, we are also examining a series of MM bone marrow tumors to evaluate the expression of novel disease markers. In addition, we are engaged in translational studies to develop novel markers for diagnosis and prognostication in MM patients. The increasing availability of small-molecule inhibitors of protein interaction may open the door to a series of clinical trials.


      • Hyperphosphorylation of BCL-2 family proteins underlies functional resistance to venetoclax in lymphoid malignancies. J Clin Invest. 2023 Sep 26. View in: Pubmed

      • Tuning ultrasmall theranostic nanoparticles for MRI contrast and radiation dose amplification. Theranostics. 2023; 13(14):4711-4729. View in: Pubmed

      • In vivo bone marrow microenvironment siRNA delivery using lipid-polymer nanoparticles for multiple myeloma therapy. Proc Natl Acad Sci U S A. 2023 06 20; 120(25):e2215711120. View in: Pubmed

      • Ubiquitin receptor PSMD4/Rpn10 is a novel therapeutic target in multiple myeloma. Blood. 2023 05 25; 141(21):2599-2614. View in: Pubmed

      • In Vivo Modeling of CLL Transformation to Richter Syndrome Reveals Convergent Evolutionary Paths and Therapeutic Vulnerabilities. Blood Cancer Discov. 2023 03 01; 4(2):150-169. View in: Pubmed

      • A novel ß-catenin/BCL9 complex inhibitor blocks oncogenic Wnt signaling and disrupts cholesterol homeostasis in colorectal cancer. Sci Adv. 2022 04 29; 8(17):eabm3108. View in: Pubmed

      • Activation of Notch and Myc Signaling via B-cell-Restricted Depletion of Dnmt3a Generates a Consistent Murine Model of Chronic Lymphocytic Leukemia. Cancer Res. 2021 12 15; 81(24):6117-6130. View in: Pubmed

      • ROBO1 Promotes Homing, Dissemination, and Survival of Multiple Myeloma within the Bone Marrow Microenvironment. Blood Cancer Discov. 2021 07; 2(4):338-353. View in: Pubmed

      • Essential role of the histone lysine demethylase KDM4A in the biology of malignant pleural mesothelioma (MPM). Br J Cancer. 2021 08; 125(4):582-592. View in: Pubmed

      • ERK signaling mediates resistance to immunomodulatory drugs in the bone marrow microenvironment. Sci Adv. 2021 06; 7(23). View in: Pubmed

      • Bortezomib induces anti-multiple myeloma immune response mediated by cGAS/STING pathway activation. Blood Cancer Discov. 2021 09; 2(5):468-483. View in: Pubmed

      • miR-15a/16-1 deletion in activated B cells promotes plasma cell and mature B-cell neoplasms. Blood. 2021 04 08; 137(14):1905-1919. View in: Pubmed

      • A hotspot mutation in transcription factor IKZF3 drives B cell neoplasia via transcriptional dysregulation. Cancer Cell. 2021 03 08; 39(3):380-393.e8. View in: Pubmed

      • Characteristic nuclear membrane ALK reactivity in chronic myelomonocytic leukemia with RANBP2-ALK fusion. Am J Hematol. 2023 02; 98(2):365-367. View in: Pubmed

      • Aggressive CD4/CD8 Double-Negative Primary Cutaneous T-Cell Lymphoma With Dural Invasion: A Rare Presentation of Mycosis Fungoides? Am J Dermatopathol. 2021 Jan 01; 43(1):63-66. View in: Pubmed

      • Multicenter phase 2 study of daratumumab monotherapy in patients with previously treated Waldenström macroglobulinemia. Blood Adv. 2020 10 27; 4(20):5089-5092. View in: Pubmed

      • HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis. J Clin Invest. 2020 07 01; 130(7):3848-3864. View in: Pubmed

      • BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins. Nat Commun. 2020 01 07; 11(1):19. View in: Pubmed

      • Human MYD88L265P is insufficient by itself to drive neoplastic transformation in mature mouse B cells. Blood Adv. 2019 11 12; 3(21):3360-3374. View in: Pubmed

      • Correction: Dual Inhibition of Canonical and Noncanonical NF-?B Pathways Demonstrates Significant Antitumor Activities in Multiple Myeloma. Clin Cancer Res. 2019 May 01; 25(9):2938. View in: Pubmed

      • Citron Rho-interacting kinase silencing causes cytokinesis failure and reduces tumor growth in multiple myeloma. Blood Adv. 2019 04 09; 3(7):995-1002. View in: Pubmed

      • A Murine Model of Chronic Lymphocytic Leukemia Based on B Cell-Restricted Expression of Sf3b1 Mutation and Atm Deletion. Cancer Cell. 2019 02 11; 35(2):283-296.e5. View in: Pubmed

      • Splicing modulation sensitizes chronic lymphocytic leukemia cells to venetoclax by remodeling mitochondrial apoptotic dependencies. JCI Insight. 2018 10 04; 3(19). View in: Pubmed

      • Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma. Cell. 2018 09 20; 175(1):101-116.e25. View in: Pubmed

      • ZMYM2-FGFR1 fusion as secondary change in acute myeloid leukemia. Leuk Lymphoma. 2019 02; 60(2):556-558. View in: Pubmed

      • MYD88 mutated and wild-type Waldenström's Macroglobulinemia: characterization of chromosome 6q gene losses and their mutual exclusivity with mutations in CXCR4. Haematologica. 2018 09; 103(9):e408-e411. View in: Pubmed

      • Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy. ACS Nano. 2018 02 27; 12(2):912-931. View in: Pubmed

      • Constitutive Ras signaling and Ink4a/Arf inactivation cooperate during the development of B-ALL in mice. Blood Adv. 2017 Nov 28; 1(25):2361-2374. View in: Pubmed

      • Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma. Leukemia. 2018 04; 32(4):996-1002. View in: Pubmed

      • A novel in vivo model for studying conditional dual loss of BLIMP-1 and p53 in B-cells, leading to tumor transformation. Am J Hematol. 2017 Aug; 92(8):E138-E145. View in: Pubmed

      • Blockade of deubiquitylating enzyme Rpn11 triggers apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Oncogene. 2017 10 05; 36(40):5631-5638. View in: Pubmed

      • Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature. 2017 03 16; 543(7645):428-432. View in: Pubmed

      • Discovery of selective small-molecule HDAC6 inhibitor for overcoming proteasome inhibitor resistance in multiple myeloma. Proc Natl Acad Sci U S A. 2016 11 15; 113(46):13162-13167. View in: Pubmed

      • Targeting proteasome ubiquitin receptor Rpn13 in multiple myeloma. Leukemia. 2016 09; 30(9):1877-86. View in: Pubmed

      • The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival. Nat Commun. 2016 Jan 05; 7:10258. View in: Pubmed

      • Evidence for a role of the histone deacetylase SIRT6 in DNA damage response of multiple myeloma cells. Blood. 2016 Mar 03; 127(9):1138-50. View in: Pubmed

      • Clonal architecture of CXCR4 WHIM-like mutations in Waldenström Macroglobulinaemia. Br J Haematol. 2016 Mar; 172(5):735-44. View in: Pubmed

      • Targeting the miR-221-222/PUMA/BAK/BAX Pathway Abrogates Dexamethasone Resistance in Multiple Myeloma. Cancer Res. 2015 Oct 15; 75(20):4384-4397. View in: Pubmed

      • The Cyclophilin A-CD147 complex promotes the proliferation and homing of multiple myeloma cells. Nat Med. 2015 Jun; 21(6):572-80. View in: Pubmed

      • Multimodality imaging and clinical features in Castleman disease: single institute experience in 30 patients. Br J Radiol. 2015 May; 88(1049):20140670. View in: Pubmed

      • Crosstalk between microRNA30a/b/c/d/e-5p and the canonical Wnt pathway: implications for multiple myeloma therapy. Cancer Res. 2014 Oct 01; 74(19):5351-8. View in: Pubmed

      • Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers. Nat Med. 2014 Jun; 20(6):599-606. View in: Pubmed

      • Transcriptional repression of plasma cell differentiation is orchestrated by aberrant over-expression of the ETS factor SPIB in Waldenström macroglobulinaemia. Br J Haematol. 2014 Sep; 166(5):677-89. View in: Pubmed

      • miR-30-5p functions as a tumor suppressor and novel therapeutic tool by targeting the oncogenic Wnt/ß-catenin/BCL9 pathway. Cancer Res. 2014 Mar 15; 74(6):1801-13. View in: Pubmed

      • A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Blood. 2014 Jan 30; 123(5):706-16. View in: Pubmed

      • Novel tumor suppressor function of glucocorticoid-induced TNF receptor GITR in multiple myeloma. PLoS One. 2013; 8(6):e66982. View in: Pubmed

      • Relative mitochondrial priming of myeloblasts and normal HSCs determines chemotherapeutic success in AML. Cell. 2012 Oct 12; 151(2):344-55. View in: Pubmed

      • A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Cancer Cell. 2012 Sep 11; 22(3):345-58. View in: Pubmed

      • Dual inhibition of canonical and noncanonical NF-?B pathways demonstrates significant antitumor activities in multiple myeloma. Clin Cancer Res. 2012 Sep 01; 18(17):4669-81. View in: Pubmed

      • Hypoxia promotes dissemination of multiple myeloma through acquisition of epithelial to mesenchymal transition-like features. Blood. 2012 Jun 14; 119(24):5782-94. View in: Pubmed

      • P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment. Blood. 2012 Feb 09; 119(6):1468-78. View in: Pubmed

      • Eph-B2/ephrin-B2 interaction plays a major role in the adhesion and proliferation of Waldenstrom's macroglobulinemia. Clin Cancer Res. 2012 Jan 01; 18(1):91-104. View in: Pubmed

      • Identification of novel myeloma-specific XBP1 peptides able to generate cytotoxic T lymphocytes: a potential therapeutic application in multiple myeloma. Leukemia. 2011 Oct; 25(10):1610-9. View in: Pubmed

      • Pathogenesis of myeloma. Annu Rev Pathol. 2011; 6:249-74. View in: Pubmed

      • PD-1 on immature and PD-1 ligands on migratory human Langerhans cells regulate antigen-presenting cell activity. J Invest Dermatol. 2010 Sep; 130(9):2222-30. View in: Pubmed

      • A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma. Blood. 2010 Jun 24; 115(25):5202-13. View in: Pubmed

      • Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target. Cancer Cell. 2009 Oct 06; 16(4):309-23. View in: Pubmed

      • International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009 Dec; 23(12):2210-21. View in: Pubmed

      • Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells. Blood. 2009 Jul 30; 114(5):1046-52. View in: Pubmed

      • Biologic sequelae of I{kappa}B kinase (IKK) inhibition in multiple myeloma: therapeutic implications. Blood. 2009 May 21; 113(21):5228-36. View in: Pubmed

      • Expression of regulatory genes for lymphoplasmacytic cell differentiation in Waldenstrom Macroglobulinemia. Br J Haematol. 2009 Apr; 145(1):59-63. View in: Pubmed

      • CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated interactions with bone marrow stromal cells. Blood. 2009 Apr 30; 113(18):4309-18. View in: Pubmed

      • Preclinical activity of P276-00, a novel small-molecule cyclin-dependent kinase inhibitor in the therapy of multiple myeloma. Leukemia. 2009 May; 23(5):961-70. View in: Pubmed

      • The Akt pathway regulates survival and homing in Waldenstrom macroglobulinemia. Blood. 2007 Dec 15; 110(13):4417-26. View in: Pubmed

      • The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis. Cancer Cell. 2007 Apr; 11(4):349-60. View in: Pubmed

      • Haploinsufficiency of the mSds3 chromatin regulator promotes chromosomal instability and cancer only upon complete neutralization of p53. Oncogene. 2006 Nov 30; 25(56):7354-60. View in: Pubmed

      • High resolution chromosome 3p, 8p, 9q and 22q allelotyping analysis in the pathogenesis of gallbladder carcinoma. Br J Cancer. 2002 Aug 12; 87(4):432-40. View in: Pubmed

      • Constitutive telomerase expression promotes mammary carcinomas in aging mice. Proc Natl Acad Sci U S A. 2002 Jun 11; 99(12):8191-6. View in: Pubmed

      • [Interferon treatment of giant hemangioma]. Cir Pediatr. 1999 Apr; 12(2):80-2. View in: Pubmed


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