Carl Novina, MD, PhD

Carl Novina, MD, PhD


Contact Information

Office Phone Number

(617) 582-7961


(617) 582-7962


Carl Novina, MD, PhD

Dr. Novina received his MD from Columbia University, College of Physicians and Surgeons in 2000 and his PhD from Tufts University, Sackler School of Graduate Biomedical Sciences in 1998. He completed his postdoctoral fellowship at the Massachusetts Institute of Technology in the laboratory of Nobel Laureate Dr. Phillip Sharp. In 2004, he joined Dana-Farber Cancer Institute & Harvard Medical School. His laboratory integrates basic science with development of advanced technologies to accelerate the translation of biological discoveries into novel therapies.



Principal Investigator, Cancer Immunology and Virology, Dana-Farber Cancer Institute
Associate Professor of Medicine, Dana-Farber Cancer Institute and Harvard Medical School
Associate Member, Broad Institute of Harvard and MIT

Medical School

  • Columbia University, College of Physicians & Surgeons

Recent Awards

  • Mentor-of-the-Year Award (2019)
  • NIH Director’s Pioneer Award (2014–19)
  • National Science Foundation Collaborative Research Project (2015–18)
  • NCI’s Provocative Questions Award (Group D, R01) (2014–18)
  • Department of Defense, Idea Development Award (2014–17)


    Epigenetic engineering cancer immunotherapy
    The Novina lab focuses on (1) the biology and dysregulation of non-coding RNAs in disease, (2) epigenetic engineering of gene expression, and (3) next-generation CAR-T therapies. We work closely with Dana-Farber clinicians to identify unmet medical needs and engineer tools that can be translated into the clinic to benefit Dana-Farber patients. Our current programs focus on developing technologies for multiple myeloma, brain and ovarian cancer therapies.
    Biology and dysregulation of non-coding RNAs: While less than 2% of our genome make proteins, more than 75% of our genome make RNAs that do not encode proteins. RNAs are often thought of as messengers to translate the information contained in DNA into proteins, which carry out many of the normal activities of the cell (coding RNAs). However, most RNAs in the cell do not make proteins (non-coding RNAs) but still play important roles in the normal activities of the cell. When altered, these non-coding RNAs can lead to disease.
    We are taking a protein-based approach to understanding the biology of these non-coding RNAs. For example, we discovered a long non-coding RNA (lncRNA) called SLNCR that mediates melanoma invasion (Cell Reports 2016 and 2020) and proliferation (Cell Reports 2019). By binding to different proteins, lncRNAs and their associated proteins control different cancer processes and regulate different genes relevant to cancer progression. Identifying their interacting proteins holds the key to discovering the underlying biology of non-coding RNA function. To accelerate our understanding of which proteins bind to which RNAs and how these might be targeted for therapy, we have developed a high-throughput platform that allows us to systematically test every protein in the human proteome against any RNA of interest.
    Epigenetic engineering of gene expression: My lab is developing another RNA-guided system, CRISPR-Cas9, for targeted recruitment of proteins that control the accessibility to and ultimately the level of expression of any gene in the human genome. The CRISPR-Cas9 system is programmable and can be used to recruit enzymes (epigenetic modifiers) that can artificially control the expression of disease-causing genes. We are working with clinicians to ‘turn-on’ genes that will make a tumor more susceptible to recognition by the immune system.
    Next-generation CAR-T therapies: Engineering patients’ T cells with ‘chimeric antigen receptors’ has shown great promise in the treatment of leukemias and lymphomas. Indeed, the complete response rate is between 70-100% in the first six months and ~50% after six months in leukemia patients receiving CAR T cell therapy. However, CAR-T cell therapies can also lead to life-threatening toxicities (e.g. cytokine storm) for some patients and unfortunately has not yet shown clinical benefit for patients with solid tumors. Our engineering strategies limit toxicities and improve the efficacy of CAR-T cell therapies.


      • A MIR17HG-derived long noncoding RNA provides an essential chromatin scaffold for protein interaction and myeloma growth. Blood. 2023 01 26; 141(4):391-405. View in: Pubmed

      • Light-Controllable Binary Switch Activation of CAR T Cells. ChemMedChem. 2022 06 20; 17(12):e202100722. View in: Pubmed

      • Clutch Control: Changing the Speed and Direction of CAR-T Cell Therapy. J Cancer Immunol (Wilmington). 2022; 4(2):52-59. View in: Pubmed

      • Genome-wide functional screen of 3'UTR variants uncovers causal variants for human disease and evolution. Cell. 2021 09 30; 184(20):5247-5260.e19. View in: Pubmed

      • Arhgef2 regulates mitotic spindle orientation in hematopoietic stem cells and is essential for productive hematopoiesis. Blood Adv. 2021 08 24; 5(16):3120-3133. View in: Pubmed

      • Author Correction: On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology. Nat Biomed Eng. 2020 Apr; 4(4):477. View in: Pubmed

      • On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology. Nat Biomed Eng. 2020 04; 4(4):394-406. View in: Pubmed

      • Targeting the Oncogenic Long Non-coding RNA SLNCR1 by Blocking Its Sequence-Specific Binding to the Androgen Receptor. Cell Rep. 2020 01 14; 30(2):541-554.e5. View in: Pubmed

      • TGFß signaling underlies hematopoietic dysfunction and bone marrow failure in Shwachman-Diamond Syndrome. J Clin Invest. 2019 06 18; 129(9):3821-3826. View in: Pubmed

      • The lncRNA SLNCR Recruits the Androgen Receptor to EGR1-Bound Genes in Melanoma and Inhibits Expression of Tumor Suppressor p21. Cell Rep. 2019 05 21; 27(8):2493-2507.e4. View in: Pubmed

      • Therapeutic discovery for marrow failure with MDS predisposition using pluripotent stem cells. JCI Insight. 2019 04 30; 5. View in: Pubmed

      • Protein engineering strategies for improving the selective methylation of target CpG sites by a dCas9-directed cytosine methyltransferase in bacteria. PLoS One. 2018; 13(12):e0209408. View in: Pubmed

      • Erratum: The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection. Nat Immunol. 2017 09 19; 18(10):1173. View in: Pubmed

      • Targeted DNA methylation in human cells using engineered dCas9-methyltransferases. Sci Rep. 2017 07 27; 7(1):6732. View in: Pubmed

      • PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer. Cancer Res. 2017 09 01; 77(17):4613-4625. View in: Pubmed

      • The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection. Nat Immunol. 2017 Jul; 18(7):791-799. View in: Pubmed

      • RATA: A method for high-throughput identification of RNA bound transcription factors. J Biol Methods. 2017; 4(1). View in: Pubmed

      • Differential Regulation of the Melanoma Proteome by eIF4A1 and eIF4E. Cancer Res. 2017 02 01; 77(3):613-622. View in: Pubmed

      • Bidirectional cross talk between patient-derived melanoma and cancer-associated fibroblasts promotes invasion and proliferation. Pigment Cell Melanoma Res. 2016 11; 29(6):656-668. View in: Pubmed

      • The lncRNA SLNCR1 Mediates Melanoma Invasion through a Conserved SRA1-like Region. Cell Rep. 2016 05 31; 15(9):2025-37. View in: Pubmed

      • Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9. Nat Med. 2016 Mar; 22(3):288-97. View in: Pubmed

      • Unique patterns of transcript and miRNA expression in the South American strong voltage electric eel (Electrophorus electricus). BMC Genomics. 2015 Mar 26; 16:243. View in: Pubmed

      • Nonhuman genetics. Genomic basis for the convergent evolution of electric organs. Science. 2014 Jun 27; 344(6191):1522-5. View in: Pubmed

      • The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia. J Exp Med. 2013 Jul 29; 210(8):1545-57. View in: Pubmed

      • miR-155 in acute myeloid leukemia: not merely a prognostic marker? J Clin Oncol. 2013 Jun 10; 31(17):2219-21. View in: Pubmed

      • Akt-mediated phosphorylation of argonaute 2 downregulates cleavage and upregulates translational repression of MicroRNA targets. Mol Cell. 2013 May 09; 50(3):356-67. View in: Pubmed

      • Alternative RISC assembly: binding and repression of microRNA-mRNA duplexes by human Ago proteins. RNA. 2012 Nov; 18(11):2041-55. View in: Pubmed

      • Reduced expression of ribosomal proteins relieves microRNA-mediated repression. Mol Cell. 2012 Apr 27; 46(2):171-86. View in: Pubmed

      • Not lost in translation: stepwise regulation of microRNA targets. EMBO J. 2012 May 30; 31(11):2446-7. View in: Pubmed

      • Feed-forward microprocessing and splicing activities at a microRNA-containing intron. PLoS Genet. 2011 Oct; 7(10):e1002330. View in: Pubmed

      • New insights into the biology of melanomas using a microRNA tool-KIT. Cell Cycle. 2011 Sep 01; 10(17):2828-9. View in: Pubmed

      • Repression of tumor suppressor miR-451 is essential for NOTCH1-induced oncogenesis in T-ALL. J Exp Med. 2011 Apr 11; 208(4):663-75. View in: Pubmed

      • MicroRNA expression profiling identifies activated B cell status in chronic lymphocytic leukemia cells. PLoS One. 2011 Mar 08; 6(3):e16956. View in: Pubmed

      • Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma. Mol Cell. 2010 Dec 10; 40(5):841-9. View in: Pubmed

      • Distinct passenger strand and mRNA cleavage activities of human Argonaute proteins. Nat Struct Mol Biol. 2009 Dec; 16(12):1259-66. View in: Pubmed

      • The chicken or the egg: microRNA-mediated regulation of mRNA translation or mRNA stability. Mol Cell. 2009 Sep 24; 35(6):739-40. View in: Pubmed

      • Comprehensive profiling of Epstein-Barr virus microRNAs in nasopharyngeal carcinoma. J Virol. 2009 Mar; 83(5):2357-67. View in: Pubmed

      • microRNA expression in the biology, prognosis, and therapy of Waldenström macroglobulinemia. Blood. 2009 Apr 30; 113(18):4391-402. View in: Pubmed

      • MicroRNA-repressed mRNAs contain 40S but not 60S components. Proc Natl Acad Sci U S A. 2008 Apr 08; 105(14):5343-8. View in: Pubmed

      • Not miR-ly small RNAs: big potential for microRNAs in therapy. J Allergy Clin Immunol. 2008 Feb; 121(2):309-19. View in: Pubmed

      • RNA-Directed Therapy: The Next Step in the miRNA Revolution. Oncologist. 2008 Jan; 13(1):1-3. View in: Pubmed

      • Analysis of microRNA effector functions in vitro. Methods. 2007 Oct; 43(2):91-104. View in: Pubmed

      • Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest. 2007 Jan; 117(1):112-21. View in: Pubmed

      • A small RNA makes a Bic difference. Genome Biol. 2007; 8(7):221. View in: Pubmed

      • Opposing functions of TFII-I spliced isoforms in growth factor-induced gene expression. Mol Cell. 2006 Oct 20; 24(2):301-8. View in: Pubmed

      • Recapitulation of short RNA-directed translational gene silencing in vitro. Mol Cell. 2006 May 19; 22(4):553-60. View in: Pubmed

      • Genetic analysis of the subunit organization and function of the conserved oligomeric golgi (COG) complex: studies of COG5- and COG7-deficient mammalian cells. J Biol Chem. 2005 Sep 23; 280(38):32736-45. View in: Pubmed

      • Potential roles for short RNAs in lymphocytes. Immunol Cell Biol. 2005 Jun; 83(3):201-10. View in: Pubmed

      • RNAi and RNA-based regulation of immune system function. Adv Immunol. 2005; 88:267-92. View in: Pubmed

      • The RNAi revolution. Nature. 2004 Jul 08; 430(6996):161-4. View in: Pubmed

      • Sustained small interfering RNA-mediated human immunodeficiency virus type 1 inhibition in primary macrophages. J Virol. 2003 Jul; 77(13):7174-81. View in: Pubmed

      • Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol. 2003 Jun; 4(6):457-67. View in: Pubmed

      • Lentivirus-delivered stable gene silencing by RNAi in primary cells. RNA. 2003 Apr; 9(4):493-501. View in: Pubmed

      • Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A. Nat Immunol. 2003 Feb; 4(2):145-53. View in: Pubmed

      • siRNA-directed inhibition of HIV-1 infection. Nat Med. 2002 Jul; 8(7):681-6. View in: Pubmed

      • Human Müllerian-inhibiting substance promoter contains a functional TFII-I-binding initiator. Biol Reprod. 2000 Oct; 63(4):1075-83. View in: Pubmed

      • Regulation of nuclear localization and transcriptional activity of TFII-I by Bruton's tyrosine kinase. Mol Cell Biol. 1999 Jul; 19(7):5014-24. View in: Pubmed

      • Regulation of TFII-I activity by phosphorylation. J Biol Chem. 1998 Dec 11; 273(50):33443-8. View in: Pubmed

      • TFII-I regulates Vbeta promoter activity through an initiator element. Mol Cell Biol. 1998 Aug; 18(8):4444-54. View in: Pubmed

      • Cloning of an inr- and E-box-binding protein, TFII-I, that interacts physically and functionally with USF1. EMBO J. 1997 Dec 01; 16(23):7091-104. View in: Pubmed

      • A multifunctional DNA-binding protein that promotes the formation of serum response factor/homeodomain complexes: identity to TFII-I. Genes Dev. 1997 Oct 01; 11(19):2482-93. View in: Pubmed

      • Methods for studying the biochemical properties of an Inr element binding protein: TFII-I. Methods. 1997 Jul; 12(3):254-63. View in: Pubmed

      • Core promoters and transcriptional control. Trends Genet. 1996 Sep; 12(9):351-5. View in: Pubmed

      • TFII is required for transcription of the naturally TATA-less but initiator-containing Vbeta promoter. J Biol Chem. 1996 May 17; 271(20):12076-81. View in: Pubmed


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      450 Brookline Avenue, Smith 570 Boston, MA 02215
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      Dana-Farber Cancer Institute

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      Dana-Farber Cancer Institute

      450 Brookline Avenue, Smith 570 Boston, MA 02215
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