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Ruben Carrasco, MD, PhD


Pathology

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Ruben Carrasco, MD, PhD

Physician

  • Associate Professor of Pathology, Harvard Medical School

Centers/Programs

Contact Information

  • Appointments877-332-4294
  • Office Phone Number617-582-8159
  • Fax617-632-6069

Bio

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.

Board Certification:

  • Anatomic Pathology, 2001
  • Hematology, 2001

Residency:

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

Medical School:

  • Universidad De Chile

Recent Awards:

  • Kimmel Award 2005

Research

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.

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.
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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.
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ROBO1 Promotes Homing, Dissemination, and Survival of Multiple Myeloma within the Bone Marrow Microenvironment. Blood Cancer Discov. 2021 07; 2(4):338-353.
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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.
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ERK signaling mediates resistance to immunomodulatory drugs in the bone marrow microenvironment. Sci Adv. 2021 06; 7(23).
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Bortezomib induces anti-multiple myeloma immune response mediated by cGAS/STING pathway activation. Blood Cancer Discov. 2021 09; 2(5):468-483.
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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.
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A hotspot mutation in transcription factor IKZF3 drives B cell neoplasia via transcriptional dysregulation. Cancer Cell. 2021 03 08; 39(3):380-393.e8.
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Characteristic nuclear membrane ALK reactivity in chronic myelomonocytic leukemia with RANBP2-ALK fusion. Am J Hematol. 2021 Jan 25.
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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.
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Multicenter phase 2 study of daratumumab monotherapy in patients with previously treated Waldenström macroglobulinemia. Blood Adv. 2020 10 27; 4(20):5089-5092.
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HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis. J Clin Invest. 2020 07 01; 130(7):3848-3864.
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BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins. Nat Commun. 2020 01 07; 11(1):19.
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Human MYD88L265P is insufficient by itself to drive neoplastic transformation in mature mouse B cells. Blood Adv. 2019 11 12; 3(21):3360-3374.
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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.
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Citron Rho-interacting kinase silencing causes cytokinesis failure and reduces tumor growth in multiple myeloma. Blood Adv. 2019 04 09; 3(7):995-1002.
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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.
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Splicing modulation sensitizes chronic lymphocytic leukemia cells to venetoclax by remodeling mitochondrial apoptotic dependencies. JCI Insight. 2018 10 04; 3(19).
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Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma. Cell. 2018 09 20; 175(1):101-116.e25.
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ZMYM2-FGFR1 fusion as secondary change in acute myeloid leukemia. Leuk Lymphoma. 2019 02; 60(2):556-558.
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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.
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Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy. ACS Nano. 2018 02 27; 12(2):912-931.
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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.
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Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma. Leukemia. 2018 04; 32(4):996-1002.
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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.
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Blockade of deubiquitylating enzyme Rpn11 triggers apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Oncogene. 2017 10 05; 36(40):5631-5638.
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Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature. 2017 03 16; 543(7645):428-432.
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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.
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Targeting proteasome ubiquitin receptor Rpn13 in multiple myeloma. Leukemia. 2016 09; 30(9):1877-86.
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The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival. Nat Commun. 2016 Jan 05; 7:10258.
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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.
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Clonal architecture of CXCR4 WHIM-like mutations in Waldenström Macroglobulinaemia. Br J Haematol. 2016 Mar; 172(5):735-44.
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Targeting the miR-221-222/PUMA/BAK/BAX Pathway Abrogates Dexamethasone Resistance in Multiple Myeloma. Cancer Res. 2015 Oct 15; 75(20):4384-4397.
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The Cyclophilin A-CD147 complex promotes the proliferation and homing of multiple myeloma cells. Nat Med. 2015 Jun; 21(6):572-80.
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Multimodality imaging and clinical features in Castleman disease: single institute experience in 30 patients. Br J Radiol. 2015 May; 88(1049):20140670.
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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.
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Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers. Nat Med. 2014 Jun; 20(6):599-606.
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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.
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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.
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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.
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Novel tumor suppressor function of glucocorticoid-induced TNF receptor GITR in multiple myeloma. PLoS One. 2013; 8(6):e66982.
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Relative mitochondrial priming of myeloblasts and normal HSCs determines chemotherapeutic success in AML. Cell. 2012 Oct 12; 151(2):344-55.
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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.
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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.
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Hypoxia promotes dissemination of multiple myeloma through acquisition of epithelial to mesenchymal transition-like features. Blood. 2012 Jun 14; 119(24):5782-94.
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P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment. Blood. 2012 Feb 09; 119(6):1468-78.
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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.
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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.
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Pathogenesis of myeloma. Annu Rev Pathol. 2011; 6:249-74.
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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.
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A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma. Blood. 2010 Jun 24; 115(25):5202-13.
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Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target. Cancer Cell. 2009 Oct 06; 16(4):309-23.
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International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009 Dec; 23(12):2210-21.
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Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells. Blood. 2009 Jul 30; 114(5):1046-52.
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Biologic sequelae of I{kappa}B kinase (IKK) inhibition in multiple myeloma: therapeutic implications. Blood. 2009 May 21; 113(21):5228-36.
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Expression of regulatory genes for lymphoplasmacytic cell differentiation in Waldenstrom Macroglobulinemia. Br J Haematol. 2009 Apr; 145(1):59-63.
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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.
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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.
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The Akt pathway regulates survival and homing in Waldenstrom macroglobulinemia. Blood. 2007 Dec 15; 110(13):4417-26.
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The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis. Cancer Cell. 2007 Apr; 11(4):349-60.
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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.
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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.
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Constitutive telomerase expression promotes mammary carcinomas in aging mice. Proc Natl Acad Sci U S A. 2002 Jun 11; 99(12):8191-6.
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[Interferon treatment of giant hemangioma]. Cir Pediatr. 1999 Apr; 12(2):80-2.
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