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Carl Novina, MD, PhD


Researcher


Researcher

  • 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

Contact Information

  • Office Phone Number(617) 582-7961
  • Fax(617) 582-7962

Bio

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.

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)

Research



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.



Chou DB, Frismantas V, Milton Y, David R, Pop-Damkov P, Ferguson D, MacDonald A, Vargel Bölükbasi Ö, Joyce CE, Moreira Teixeira LS, Rech A, Jiang A, Calamari E, Jalili-Firoozinezhad S, Furlong BA, O'Sullivan LR, Ng CF, Choe Y, Marquez S, Myers KC, Weinberg OK, Hasserjian RP, Novak R, Levy O, Prantil-Baun R, Novina CD, Shimamura A, Ewart L, Ingber DE. Author Correction: On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology. Nat Biomed Eng. 2020 Apr; 4(4):477.
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Chou DB, Frismantas V, Milton Y, David R, Pop-Damkov P, Ferguson D, MacDonald A, Vargel Bölükbasi Ö, Joyce CE, Moreira Teixeira LS, Rech A, Jiang A, Calamari E, Jalili-Firoozinezhad S, Furlong BA, O'Sullivan LR, Ng CF, Choe Y, Marquez S, Myers KC, Weinberg OK, Hasserjian RP, Novak R, Levy O, Prantil-Baun R, Novina CD, Shimamura A, Ewart L, Ingber DE. On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology. Nat Biomed Eng. 2020 04; 4(4):394-406.
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Schmidt K, Weidmann CA, Hilimire TA, Yee E, Hatfield BM, Schneekloth JS, Weeks KM, Novina CD. 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.
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Joyce CE, Saadatpour A, Ruiz-Gutierrez M, Bolukbasi OV, Jiang L, Thomas DD, Young S, Hofmann I, Sieff CA, Myers KC, Whangbo J, Libermann TA, Nusbaum C, Yuan GC, Shimamura A, Novina CD. TGFß signaling underlies hematopoietic dysfunction and bone marrow failure in Shwachman-Diamond Syndrome. J Clin Invest. 2019 06 18; 129(9):3821-3826.
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Schmidt K, Carroll JS, Yee E, Thomas DD, Wert-Lamas L, Neier SC, Sheynkman G, Ritz J, Novina CD. 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.
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Ruiz-Gutierrez M, Bölükbasi ÖV, Alexe G, Kotini AG, Ballotti K, Joyce CE, Russell DW, Stegmaier K, Myers K, Novina CD, Papapetrou EP, Shimamura A. Therapeutic discovery for marrow failure with MDS predisposition using pluripotent stem cells. JCI Insight. 2019 04 30; 5.
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Xiong T, Rohm D, Workman RE, Roundtree L, Novina CD, Timp W, Ostermeier M. 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.
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Moffett HF, Cartwright ANR, Kim HJ, Godec J, Pyrdol J, Äijö T, Martinez GJ, Rao A, Lu J, Golub TR, Cantor H, Sharpe AH, Novina CD, Wucherpfennig KW. Erratum: The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection. Nat Immunol. 2017 09 19; 18(10):1173.
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Xiong T, Meister GE, Workman RE, Kato NC, Spellberg MJ, Turker F, Timp W, Ostermeier M, Novina CD. Targeted DNA methylation in human cells using engineered dCas9-methyltransferases. Sci Rep. 2017 07 27; 7(1):6732.
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Hsu JH, Hubbell-Engler B, Adelmant G, Huang J, Joyce CE, Vazquez F, Weir BA, Montgomery P, Tsherniak A, Giacomelli AO, Perry JA, Trowbridge J, Fujiwara Y, Cowley GS, Xie H, Kim W, Novina CD, Hahn WC, Marto JA, Orkin SH. PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer. Cancer Res. 2017 09 01; 77(17):4613-4625.
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Moffett HF, Cartwright ANR, Kim HJ, Godec J, Pyrdol J, Äijö T, Martinez GJ, Rao A, Lu J, Golub TR, Cantor H, Sharpe AH, Novina CD, Wucherpfennig KW. The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection. Nat Immunol. 2017 Jul; 18(7):791-799.
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Schmidt K, Buquicchio F, Carroll JS, Distel RJ, Novina CD. RATA: A method for high-throughput identification of RNA bound transcription factors. J Biol Methods. 2017; 4(1).
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Joyce CE, Yanez AG, Mori A, Yoda A, Carroll JS, Novina CD. Differential Regulation of the Melanoma Proteome by eIF4A1 and eIF4E. Cancer Res. 2017 02 01; 77(3):613-622.
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Izar B, Joyce CE, Goff S, Cho NL, Shah PM, Sharma G, Li J, Ibrahim N, Gold J, Hodi FS, Garraway LA, Novina CD, Bertagnolli MM, Yoon CH. 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.
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Schmidt K, Joyce CE, Buquicchio F, Brown A, Ritz J, Distel RJ, Yoon CH, Novina CD. The lncRNA SLNCR1 Mediates Melanoma Invasion through a Conserved SRA1-like Region. Cell Rep. 2016 05 31; 15(9):2025-37.
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Schneider RK, Schenone M, Ferreira MV, Kramann R, Joyce CE, Hartigan C, Beier F, Brümmendorf TH, Germing U, Platzbecker U, Büsche G, Knüchel R, Chen MC, Waters CS, Chen E, Chu LP, Novina CD, Lindsley RC, Carr SA, Ebert BL. Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9. Nat Med. 2016 Mar; 22(3):288-97.
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Traeger LL, Volkening JD, Moffett H, Gallant JR, Chen PH, Novina CD, Phillips GN, Anand R, Wells GB, Pinch M, Güth R, Unguez GA, Albert JS, Zakon H, Sussman MR, Samanta MP. Unique patterns of transcript and miRNA expression in the South American strong voltage electric eel (Electrophorus electricus). BMC Genomics. 2015 Mar 26; 16:243.
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Gallant JR, Traeger LL, Volkening JD, Moffett H, Chen PH, Novina CD, Phillips GN, Anand R, Wells GB, Pinch M, Güth R, Unguez GA, Albert JS, Zakon HH, Samanta MP, Sussman MR. Nonhuman genetics. Genomic basis for the convergent evolution of electric organs. Science. 2014 Jun 27; 344(6191):1522-5.
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Mansour MR, Sanda T, Lawton LN, Li X, Kreslavsky T, Novina CD, Brand M, Gutierrez A, Kelliher MA, Jamieson CH, von Boehmer H, Young RA, Look AT. 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.
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Joyce CE, Novina CD. miR-155 in acute myeloid leukemia: not merely a prognostic marker? J Clin Oncol. 2013 Jun 10; 31(17):2219-21.
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Horman SR, Janas MM, Litterst C, Wang B, MacRae IJ, Sever MJ, Morrissey DV, Graves P, Luo B, Umesalma S, Qi HH, Miraglia LJ, Novina CD, Orth AP. Akt-mediated phosphorylation of argonaute 2 downregulates cleavage and upregulates translational repression of MicroRNA targets. Mol Cell. 2013 May 09; 50(3):356-67.
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Janas MM, Wang B, Harris AS, Aguiar M, Shaffer JM, Subrahmanyam YV, Behlke MA, Wucherpfennig KW, Gygi SP, Gagnon E, Novina CD. Alternative RISC assembly: binding and repression of microRNA-mRNA duplexes by human Ago proteins. RNA. 2012 Nov; 18(11):2041-55.
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Janas MM, Wang E, Love T, Harris AS, Stevenson K, Semmelmann K, Shaffer JM, Chen PH, Doench JG, Yerramilli SV, Neuberg DS, Iliopoulos D, Housman DE, Burge CB, Novina CD. Reduced expression of ribosomal proteins relieves microRNA-mediated repression. Mol Cell. 2012 Apr 27; 46(2):171-86.
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Janas MM, Novina CD. Not lost in translation: stepwise regulation of microRNA targets. EMBO J. 2012 May 30; 31(11):2446-7.
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Janas MM, Khaled M, Schubert S, Bernstein JG, Golan D, Veguilla RA, Fisher DE, Shomron N, Levy C, Novina CD. Feed-forward microprocessing and splicing activities at a microRNA-containing intron. PLoS Genet. 2011 Oct; 7(10):e1002330.
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Novina CD. New insights into the biology of melanomas using a microRNA tool-KIT. Cell Cycle. 2011 Sep 01; 10(17):2828-9.
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Li X, Sanda T, Look AT, Novina CD, von Boehmer H. 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.
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Li S, Moffett HF, Lu J, Werner L, Zhang H, Ritz J, Neuberg D, Wucherpfennig KW, Brown JR, Novina CD. MicroRNA expression profiling identifies activated B cell status in chronic lymphocytic leukemia cells. PLoS One. 2011 Mar 08; 6(3):e16956.
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Levy C, Khaled M, Iliopoulos D, Janas MM, Schubert S, Pinner S, Chen PH, Li S, Fletcher AL, Yokoyama S, Scott KL, Garraway LA, Song JS, Granter SR, Turley SJ, Fisher DE, Novina CD. Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma. Mol Cell. 2010 Dec 10; 40(5):841-9.
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Wang B, Li S, Qi HH, Chowdhury D, Shi Y, Novina CD. Distinct passenger strand and mRNA cleavage activities of human Argonaute proteins. Nat Struct Mol Biol. 2009 Dec; 16(12):1259-66.
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Omer AD, Janas MM, Novina CD. The chicken or the egg: microRNA-mediated regulation of mRNA translation or mRNA stability. Mol Cell. 2009 Sep 24; 35(6):739-40.
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Cosmopoulos K, Pegtel M, Hawkins J, Moffett H, Novina C, Middeldorp J, Thorley-Lawson DA. Comprehensive profiling of Epstein-Barr virus microRNAs in nasopharyngeal carcinoma. J Virol. 2009 Mar; 83(5):2357-67.
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Roccaro AM, Sacco A, Chen C, Runnels J, Leleu X, Azab F, Azab AK, Jia X, Ngo HT, Melhem MR, Burwick N, Varticovski L, Novina CD, Rollins BJ, Anderson KC, Ghobrial IM. microRNA expression in the biology, prognosis, and therapy of Waldenström macroglobulinemia. Blood. 2009 Apr 30; 113(18):4391-402.
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Wang B, Yanez A, Novina CD. MicroRNA-repressed mRNAs contain 40S but not 60S components. Proc Natl Acad Sci U S A. 2008 Apr 08; 105(14):5343-8.
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Love TM, Moffett HF, Novina CD. Not miR-ly small RNAs: big potential for microRNAs in therapy. J Allergy Clin Immunol. 2008 Feb; 121(2):309-19.
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Novina CD, Chabner BA. RNA-Directed Therapy: The Next Step in the miRNA Revolution. Oncologist. 2008 Jan; 13(1):1-3.
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Wang B, Doench JG, Novina CD. Analysis of microRNA effector functions in vitro. Methods. 2007 Oct; 43(2):91-104.
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Del Gaizo Moore V, Brown JR, Certo M, Love TM, Novina CD, Letai A. 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.
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Moffett HF, Novina CD. A small RNA makes a Bic difference. Genome Biol. 2007; 8(7):221.
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Hakre S, Tussie-Luna MI, Ashworth T, Novina CD, Settleman J, Sharp PA, Roy AL. Opposing functions of TFII-I spliced isoforms in growth factor-induced gene expression. Mol Cell. 2006 Oct 20; 24(2):301-8.
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Wang B, Love TM, Call ME, Doench JG, Novina CD. Recapitulation of short RNA-directed translational gene silencing in vitro. Mol Cell. 2006 May 19; 22(4):553-60.
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Oka T, Vasile E, Penman M, Novina CD, Dykxhoorn DM, Ungar D, Hughson FM, Krieger M. 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.
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Chowdhury D, Novina CD. Potential roles for short RNAs in lymphocytes. Immunol Cell Biol. 2005 Jun; 83(3):201-10.
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Chowdhury D, Novina CD. RNAi and RNA-based regulation of immune system function. Adv Immunol. 2005; 88:267-92.
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Novina CD, Sharp PA. The RNAi revolution. Nature. 2004 Jul 08; 430(6996):161-4.
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Song E, Lee SK, Dykxhoorn DM, Novina C, Zhang D, Crawford K, Cerny J, Sharp PA, Lieberman J, Manjunath N, Shankar P. Sustained small interfering RNA-mediated human immunodeficiency virus type 1 inhibition in primary macrophages. J Virol. 2003 Jul; 77(13):7174-81.
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Dykxhoorn DM, Novina CD, Sharp PA. Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol. 2003 Jun; 4(6):457-67.
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Stewart SA, Dykxhoorn DM, Palliser D, Mizuno H, Yu EY, An DS, Sabatini DM, Chen IS, Hahn WC, Sharp PA, Weinberg RA, Novina CD. Lentivirus-delivered stable gene silencing by RNAi in primary cells. RNA. 2003 Apr; 9(4):493-501.
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Fan Z, Beresford PJ, Zhang D, Xu Z, Novina CD, Yoshida A, Pommier Y, Lieberman J. Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A. Nat Immunol. 2003 Feb; 4(2):145-53.
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Novina CD, Murray MF, Dykxhoorn DM, Beresford PJ, Riess J, Lee SK, Collman RG, Lieberman J, Shankar P, Sharp PA. siRNA-directed inhibition of HIV-1 infection. Nat Med. 2002 Jul; 8(7):681-6.
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Morikawa N, Clarke TR, Novina CD, Watanabe K, Haqq C, Weiss M, Roy AL, Donahoe PK. Human Müllerian-inhibiting substance promoter contains a functional TFII-I-binding initiator. Biol Reprod. 2000 Oct; 63(4):1075-83.
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Novina CD, Kumar S, Bajpai U, Cheriyath V, Zhang K, Pillai S, Wortis HH, Roy AL. Regulation of nuclear localization and transcriptional activity of TFII-I by Bruton's tyrosine kinase. Mol Cell Biol. 1999 Jul; 19(7):5014-24.
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Novina CD, Cheriyath V, Roy AL. Regulation of TFII-I activity by phosphorylation. J Biol Chem. 1998 Dec 11; 273(50):33443-8.
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Cheriyath V, Novina CD, Roy AL. TFII-I regulates Vbeta promoter activity through an initiator element. Mol Cell Biol. 1998 Aug; 18(8):4444-54.
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Roy AL, Du H, Gregor PD, Novina CD, Martinez E, Roeder RG. 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.
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Grueneberg DA, Henry RW, Brauer A, Novina CD, Cheriyath V, Roy AL, Gilman M. 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.
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Novina CD, Cheriyath V, Denis MC, Roy AL. Methods for studying the biochemical properties of an Inr element binding protein: TFII-I. Methods. 1997 Jul; 12(3):254-63.
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Novina CD, Roy AL. Core promoters and transcriptional control. Trends Genet. 1996 Sep; 12(9):351-5.
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Manzano-Winkler B, Novina CD, Roy AL. 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.
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