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Ruben Carrasco, MD, PhD


Oncologic Pathology

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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

Location

Dana-Farber Cancer Institute
450 Brookline Avenue
Jimmy Fund Building 215H
Boston MA, 02215
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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.

Guimarães PPG, Gaglione S, Sewastianik T, Carrasco RD, Langer R, Mitchell MJ. Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy. ACS Nano. 2018 Feb 06.
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Gullà A, Hideshima T, Bianchi G, Fulciniti M, Kemal Samur M, Qi J, Tai YT, Harada T, Morelli E, Amodio N, Carrasco R, Tagliaferri P, Munshi NC, Tassone P, Anderson KC. Protein arginine methyltransferase 5 has prognostic relevance and is a druggable target in multiple myeloma. Leukemia. 2017 Nov 21.
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Sewastianik T, Jiang M, Sukhdeo K, Patel SS, Roberts K, Kang Y, Alduaij A, Dennis PS, Lawney B, Liu R, Song Z, Xiong J, Zhang Y, Lemieux ME, Pinkus GS, Rich JN, Weinstock DM, Mullighan CG, Sharpless NE, Carrasco RD. 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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Sacco A, Kawano Y, Moschetta M, Zavidij O, Huynh D, Reagan M, Mishima Y, Manier S, Park J, Morgan E, Takagi S, Wong KK, Carrasco R, Ghobrial IM, Roccaro AM. 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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Song Y, Li S, Ray A, Das DS, Qi J, Samur MK, Tai YT, Munshi N, Carrasco RD, Chauhan D, Anderson KC. Blockade of deubiquitylating enzyme Rpn11 triggers apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Oncogene. 2017 Oct 05; 36(40):5631-5638.
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Guerriero JL, Sotayo A, Ponichtera HE, Castrillon JA, Pourzia AL, Schad S, Johnson SF, Carrasco RD, Lazo S, Bronson RT, Davis SP, Lobera M, Nolan MA, Letai A. 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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Hideshima T, Qi J, Paranal RM, Tang W, Greenberg E, West N, Colling ME, Estiu G, Mazitschek R, Perry JA, Ohguchi H, Cottini F, Mimura N, Görgün G, Tai YT, Richardson PG, Carrasco RD, Wiest O, Schreiber SL, Anderson KC, Bradner JE. Discovery of selective small-molecule HDAC6 inhibitor for overcoming proteasome inhibitor resistance in multiple myeloma. Proc Natl Acad Sci U S A. 2016 Nov 15; 113(46):13162-13167.
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Song Y, Ray A, Li S, Das DS, Tai YT, Carrasco RD, Chauhan D, Anderson KC. Targeting proteasome ubiquitin receptor Rpn13 in multiple myeloma. Leukemia. 2016 09; 30(9):1877-86.
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Ohguchi H, Hideshima T, Bhasin MK, Gorgun GT, Santo L, Cea M, Samur MK, Mimura N, Suzuki R, Tai YT, Carrasco RD, Raje N, Richardson PG, Munshi NC, Harigae H, Sanda T, Sakai J, Anderson KC. The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival. Nat Commun. 2016 Jan 05; 7:10258.
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Cea M, Cagnetta A, Adamia S, Acharya C, Tai YT, Fulciniti M, Ohguchi H, Munshi A, Acharya P, Bhasin MK, Zhong L, Carrasco R, Monacelli F, Ballestrero A, Richardson P, Gobbi M, Lemoli RM, Munshi N, Hideshima T, Nencioni A, Chauhan D, Anderson KC. 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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Xu L, Hunter ZR, Tsakmaklis N, Cao Y, Yang G, Chen J, Liu X, Kanan S, Castillo JJ, Tai YT, Zehnder JL, Brown JR, Carrasco RD, Advani R, Sabile JM, Argyropoulos K, Lia Palomba M, Morra E, Trojani A, Greco A, Tedeschi A, Varettoni M, Arcaini L, Munshi NM, Anderson KC, Treon SP. Clonal architecture of CXCR4 WHIM-like mutations in Waldenström Macroglobulinaemia. Br J Haematol. 2016 Mar; 172(5):735-44.
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Zhao JJ, Chu ZB, Hu Y, Lin J, Wang Z, Jiang M, Chen M, Wang X, Kang Y, Zhou Y, Ni Chonghaile T, Johncilla ME, Tai YT, Cheng JQ, Letai A, Munshi NC, Anderson KC, Carrasco RD. 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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Zhu D, Wang Z, Zhao JJ, Calimeri T, Meng J, Hideshima T, Fulciniti M, Kang Y, Ficarro SB, Tai YT, Hunter Z, McMilin D, Tong H, Mitsiades CS, Wu CJ, Treon SP, Dorfman DM, Pinkus G, Munshi NC, Tassone P, Marto JA, Anderson KC, Carrasco RD. 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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Hill AJ, Tirumani SH, Rosenthal MH, Shinagare AB, Carrasco RD, Munshi NC, Ramaiya NH, Howard SA. 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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Zhao JJ, Carrasco RD. 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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Cottini F, Hideshima T, Xu C, Sattler M, Dori M, Agnelli L, ten Hacken E, Bertilaccio MT, Antonini E, Neri A, Ponzoni M, Marcatti M, Richardson PG, Carrasco R, Kimmelman AC, Wong KK, Caligaris-Cappio F, Blandino G, Kuehl WM, Anderson KC, Tonon G. 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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Zhou Y, Liu X, Xu L, Hunter ZR, Cao Y, Yang G, Carrasco R, Treon SP. 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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Zhao JJ, Lin J, Zhu D, Wang X, Brooks D, Chen M, Chu ZB, Takada K, Ciccarelli B, Admin S, Tao J, Tai YT, Treon S, Pinkus G, Kuo WP, Hideshima T, Bouxsein M, Munshi N, Anderson K, Carrasco R. 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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Tian Z, D'Arcy P, Wang X, Ray A, Tai YT, Hu Y, Carrasco RD, Richardson P, Linder S, Chauhan D, Anderson KC. 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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Liu Y, Quang P, Braggio E, Ngo H, Badalian-Very G, Flores L, Zhang Y, Sacco A, Maiso P, Azab AK, Azab F, Carrasco R, Rollins BJ, Roccaro AM, Ghobrial IM. Novel tumor suppressor function of glucocorticoid-induced TNF receptor GITR in multiple myeloma. PLoS One. 2013; 8(6):e66982.
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Vo TT, Ryan J, Carrasco R, Neuberg D, Rossi DJ, Stone RM, Deangelo DJ, Frattini MG, Letai A. 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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Chauhan D, Tian Z, Nicholson B, Kumar KG, Zhou B, Carrasco R, McDermott JL, Leach CA, Fulcinniti M, Kodrasov MP, Weinstock J, Kingsbury WD, Hideshima T, Shah PK, Minvielle S, Altun M, Kessler BM, Orlowski R, Richardson P, Munshi N, Anderson KC. 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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Fabre C, Mimura N, Bobb K, Kong SY, Gorgun G, Cirstea D, Hu Y, Minami J, Ohguchi H, Zhang J, Meshulam J, Carrasco RD, Tai YT, Richardson PG, Hideshima T, Anderson KC. 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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Azab AK, Hu J, Quang P, Azab F, Pitsillides C, Awwad R, Thompson B, Maiso P, Sun JD, Hart CP, Roccaro AM, Sacco A, Ngo HT, Lin CP, Kung AL, Carrasco RD, Vanderkerken K, Ghobrial IM. 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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Azab AK, Quang P, Azab F, Pitsillides C, Thompson B, Chonghaile T, Patton JT, Maiso P, Monrose V, Sacco A, Ngo HT, Flores LM, Lin CP, Magnani JL, Kung AL, Letai A, Carrasco R, Roccaro AM, Ghobrial IM. 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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Azab F, Azab AK, Maiso P, Calimeri T, Flores L, Liu Y, Quang P, Roccaro AM, Sacco A, Ngo HT, Zhang Y, Morgan BL, Carrasco RD, Ghobrial IM. 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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Bae J, Carrasco R, Lee AH, Prabhala R, Tai YT, Anderson KC, Munshi NC. 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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Anderson KC, Carrasco RD. Pathogenesis of myeloma. Annu Rev Pathol. 2011; 6:249-74.
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Peña-Cruz V, McDonough SM, Diaz-Griffero F, Crum CP, Carrasco RD, Freeman GJ. 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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Görgün G, Calabrese E, Hideshima T, Ecsedy J, Perrone G, Mani M, Ikeda H, Bianchi G, Hu Y, Cirstea D, Santo L, Tai YT, Nahar S, Zheng M, Bandi M, Carrasco RD, Raje N, Munshi N, Richardson P, Anderson KC. 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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Chauhan D, Singh AV, Brahmandam M, Carrasco R, Bandi M, Hideshima T, Bianchi G, Podar K, Tai YT, Mitsiades C, Raje N, Jaye DL, Kumar SK, Richardson P, Munshi N, Anderson KC. 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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Fonseca R, Bergsagel PL, Drach J, Shaughnessy J, Gutierrez N, Stewart AK, Morgan G, Van Ness B, Chesi M, Minvielle S, Neri A, Barlogie B, Kuehl WM, Liebisch P, Davies F, Chen-Kiang S, Durie BG, Carrasco R, Sezer O, Reiman T, Pilarski L, Avet-Loiseau H. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009 Dec; 23(12):2210-21.
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Hideshima T, Ikeda H, Chauhan D, Okawa Y, Raje N, Podar K, Mitsiades C, Munshi NC, Richardson PG, Carrasco RD, Anderson KC. Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells. Blood. 2009 Jul 30; 114(5):1046-52.
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Hideshima T, Chauhan D, Kiziltepe T, Ikeda H, Okawa Y, Podar K, Raje N, Protopopov A, Munshi NC, Richardson PG, Carrasco RD, Anderson KC. 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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Leleu X, Hunter ZR, Xu L, Roccaro AM, Moreau AS, Santos DD, Hatjiharissi E, Bakthavachalam V, Adamia S, Ho AW, Soumerai J, Patterson CJ, Manning RJ, Hamilton S, Verselis S, Fox E, Carrasco R, Ghobrial IM, Treon SP. Expression of regulatory genes for lymphoplasmacytic cell differentiation in Waldenstrom Macroglobulinemia. Br J Haematol. 2009 Apr; 145(1):59-63.
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Tai YT, Soydan E, Song W, Fulciniti M, Kim K, Hong F, Li XF, Burger P, Rumizen MJ, Nahar S, Podar K, Hideshima T, Munshi NC, Tonon G, Carrasco RD, Afar DE, Anderson KC. 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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Raje N, Hideshima T, Mukherjee S, Raab M, Vallet S, Chhetri S, Cirstea D, Pozzi S, Mitsiades C, Rooney M, Kiziltepe T, Podar K, Okawa Y, Ikeda H, Carrasco R, Richardson PG, Chauhan D, Munshi NC, Sharma S, Parikh H, Chabner B, Scadden D, Anderson KC. 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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Leleu X, Jia X, Runnels J, Ngo HT, Moreau AS, Farag M, Spencer JA, Pitsillides CM, Hatjiharissi E, Roccaro A, O'Sullivan G, McMillin DW, Moreno D, Kiziltepe T, Carrasco R, Treon SP, Hideshima T, Anderson KC, Lin CP, Ghobrial IM. The Akt pathway regulates survival and homing in Waldenstrom macroglobulinemia. Blood. 2007 Dec 15; 110(13):4417-26.
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Carrasco DR, Sukhdeo K, Protopopova M, Sinha R, Enos M, Carrasco DE, Zheng M, Mani M, Henderson J, Pinkus GS, Munshi N, Horner J, Ivanova EV, Protopopov A, Anderson KC, Tonon G, DePinho RA. The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis. Cancer Cell. 2007 Apr; 11(4):349-60.
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David G, Dannenberg JH, Simpson N, Finnerty PM, Miao L, Turner GM, Ding Z, Carrasco R, Depinho RA. 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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Artandi SE, Alson S, Tietze MK, Sharpless NE, Ye S, Greenberg RA, Castrillon DH, Horner JW, Weiler SR, Carrasco RD, DePinho RA. 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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