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Jason X. Cheng

TitleAssociate Professor
InstitutionUniversity of Chicago
DepartmentPathology
AddressChicago IL 60637
Phone+1 (773) 7021254
Email
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    Collapse Overview 
    Collapse overview
    Dr. Cheng is a board-certified pathologist in Anatomic Pathology and Clinical Pathology (AP/CP) as well as in Hematology/Hematopathology. His clinical and research interests focus on hematologic diseases, including myelodysplastic syndromes (MDS), aplastic anemia/bone marrow failure, myeloproliferative neoplasms (MPN) and acute myeloid leukemia (AML). Some highlights of his academic career include: 1. Invention of a novel technology to identify sequence-specific DNA-binding peptides for transcriptional regulation and gene editing (U.S. patent no 5,869,250. Filing date: 1996/12/02; Granted date: 1999/02/09); 2. The first discovery of INI1/hSNF5/ SMARCB1 loss as a hallmark for renal medullary carcinoma (Modern Pathology, 2008); 3. Conducting the first genome-wide epigenetic profiling of MDS specimens (the 2008 USCAP-SH Pathologist-in-Training Award and the 2008 Paul E. Strandjord Young Investigator Award); 4. Receiving the Cancer Research Foundation Young Investigator Award, the Swim Across America-Rush University/University of Chicago Cancer Research Award and the Michael Reese Foundation Bench-to-Bedside Translational Science Award for exploring chromatin structure-based epigenetic diagnostics and therapeutics in MDS and AML; and 5. Discovery of RNA 5-methylcytsoine (RNA:m5C) methyltransferases (NSUN1 and NSUN2)-mediated drug-responsive/resistant chromatin structures in MDS and AML (Nature Communications 2018) and receiving the 2019 Taub Medical Foundation MDS Award to study the role of RNA:m5C and its methyltransferases in MDS.

    The current focus of Dr. Cheng’s research is on elucidating the role of RNA epigenetics, more specifically RNA:m5C and its writers NSUN1 (NOP2/NOL1) and NSUN2, in the regulation of cellular organelle structures and functions, and developing novel RNA epigenetics-driven diagnostics and therapeutics for cancer/leukemia and other human diseases. Both NSUN1 and NSUN2 methylate cytosine residues in various RNA species to regulate multiple essential bioprocesses, including chromatin organization, gene expression, and mitochondrial metabolism, and play an important role in cell/organ development, tumor immune evasion, metastasis and drug resistance (Willbanks A, Wood S, Cheng JX. Genes. 2021). Dr. Cheng’s lab has developed novel nascent RNA-driven flow imaging technologies, NSUN1/2 expression cell lines and Nsun2 knockout (KO) mouse models, which provide valuable tools to dissect the RNA:m5C and NSUN1/2-mediated chromatin structure, transcription, translation and metabolism, and to explore the clinical potential of RNA epigenetics-driven diagnostics and therapeutics in various human diseases. More recently, in collaboration with Professor Rick Stevens at the Argonne National Laboratory (ANL), Dr. Cheng’s lab leveraged the Argonne artificial Intelligence (AI) supercomputer and novel RNA epigenetics-driven technologies to design and screen small-molecule compound libraries that target the computationally predicted ligand-binding surfaces/modules in NSUN1 and NSUN2 proteins. They have identified several selective small-molecule inhibitors of NSUN1 and NSUN2 and demonstrated a high efficacy of the NSUN1/2 inhibitors in killing drug-resistant leukemia cells using in vitro cell lines and in vivo syngeneic AML mouse models. Those novel RNA epigenetics-driven technologies and small-molecule inhibitors hold a high-promise for development of novel NSUN1/2/RNA epigenetics-driven novel diagnostics and therapeutics for leukemia and cancer.

    Collapse Biography 
    Collapse education and training
    University of Chicago, ChicagoClinical Fellowship mentored by Dr. James Vardiman06/2010Hematopathology
    University of Chicago, ChicagoResidency 07/2008Anatomic and Clinical Pathology (AP/CP)
    Memorial Sloan Kettering Cancer Center, New YorkPost-doc in Dr. Mark Ptashne Lab06/2004Molecular Biology & Yeast Genetics
    University of North Carolina, Chapel HillPost-doc in Dr. Rudy Juliano Lab08/1999Pharmacology
    University of North Carolina, Chapel HillPhD mentored by Dr. Rudy Juliano08/1997Pharmacology
    University of North Carolina, Chapel HillResearch Fellow08/1993Pathology
    People’s Hospital of Beijing Medical University, BeijingInstructor08/1992Pathology
    Beijing Medical University, BeijingMaster of Science (MS) mentored by Dr. Guo Quanxin08/1990Pathology
    Yunnan Red Cross Hospital, KunmingResidency08/1987Surgery
    Kunming Medical University, KunmingBachelor (MD equivalent)08/1983Medicine
    Collapse awards and honors
    2007The Robert E. Priest Fellowship, University of Chicago
    2007The winner of Chicago Pathology Society Resident Research Awards, Chicago Pathology Society
    2008The Pathologist-in-Training Award, Society for Hematopathology/United States and Canadian Academy of Pathology (USACP)
    2008The Paul E. Strandjord Young Investigator Award, Academy of Clinical Physicians and Scientists
    2008The USCAP Best Abstract Award, The International Association of Chinese Pathologists
    2012The Best Oral Platform Presentation, The American Society for Clinical Pathology
    2013The American Cancer Society (ACS-IRG) Award, University of Chicago
    2014The American Cancer Society (ACS-IRG), University of Chicago
    2014The Young Investigator Award, Cancer Research Foundation
    2016The Swim Across America: Rush University/UChicago ITM Pilot Award, Swim Across America.org
    2019The Michael Reese Bench-to-Bedside Translational Science Award, Michael Reese Foundation
    2019The Taub Medical foundation for MDS program Awards, The Henry and Marilyn Taub Foundation

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Johnston H, Rahmani Youshanlouei H, Osei C, Patel AA, DuVall AS, Wang P, Wanjari P, Segal JP, Venkataraman G, Cheng JX, Gurbuxani S, Lager AM, Fitzpatrick C, Thirman MJ, Nawas MT, Liu H, Drazer MW, Odenike O, Larson RA, Stock W, Saygin C, Johnston H, Youshanlouei HR, Osei C, Patel AA, DuVall A, Wang P, Wanjari P, Segal J, Venkataraman G, Cheng JX, Gurbuxani S, Lager A, Fitzpatrick C, Thirman M, Nawas M, Liu H, Drazer M, Odenike O, Larson R, Stock W, Saygin C. Socioeconomic determinants of the biology and outcomes of acute lymphoblastic leukemia in adults. Blood Adv. 2024 01 09; 8(1):164-171. PMID: 38039510; PMCID: PMC10787242.
      Citations:    Fields:    Translation:Humans
    2. Saygin C, Zhang P, Stauber J, Aldoss I, Sperling AS, Weeks LD, Luskin MR, Knepper TC, Wanjari P, Wang P, Lager AM, Fitzpatrick C, Segal JP, Gharghabi M, Gurbuxani S, Venkataraman G, Cheng JX, Eisfelder BJ, Bohorquez O, Patel AA, Umesh Nagalakshmi S, Jayaram S, Odenike OM, Larson RA, Godley LA, Arber DA, Gibson CJ, Munshi NC, Marcucci G, Ebert BL, Greally JM, Steidl U, Lapalombella R, Shah BD, Stock W. Acute lymphoblastic leukemia with myeloid mutations is a high-risk disease associated with clonal hematopoiesis. Blood Cancer Discov. 2023 Dec 27. PMID: 38150184.
      Citations:    Fields:    
    3. Cohen NA, Weber CR, Cheng JX, Choi D, Garcia NM, Choi NK, Rubin DT. Ozanimod-Exposed Patients with Ulcerative Colitis Undergoing Total Colectomy Exhibit Unique Lymph Node Histologic Changes. J Crohns Colitis. 2023 Oct 25. PMID: 37879626.
      Citations:    Fields:    
    4. Kaumeyer BA, Fidai SS, Thakral B, Wang SA, Arber DA, Cheng JX, Gurbuxani S, Venkataraman G. GLUT1 Immunohistochemistry Is a Highly Sensitive and Relatively Specific Marker for Erythroid Lineage in Benign and Malignant Hematopoietic Tissues. Am J Clin Pathol. 2022 08 04; 158(2):228-234. PMID: 35311938.
      Citations:    Fields:    Translation:Humans
    5. Willbanks A, Wood S, Cheng JX. RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases. Genes (Basel). 2021 04 22; 12(5). PMID: 33922187; PMCID: PMC8145807.
      Citations: 9     Fields:    Translation:HumansAnimalsCells
    6. Eisfelder BJ, Saygin C, Wynne J, Colton MW, Fischietti M, Beauchamp EM, Cheng JX, Odenike O, Roboz G, Alachkar H, Stock W. OTS167 blocks FLT3 translation and synergizes with FLT3 inhibitors in FLT3 mutant acute myeloid leukemia. Blood Cancer J. 2021 03 03; 11(3):48. PMID: 33658483; PMCID: PMC7930094.
      Citations: 2     Fields:    Translation:HumansAnimalsCells
    7. Willbank A, Wood S, Cheng JX. Development of a Novel Flow Cytometric Technique for Quantitative Measurements of Transcriptional Addiction and Drug Resistance in Leukemia Cells. Modern Pathology. 2021; 34(2):927-1049.
    8. Wood S, Willbanks A, Cheng JX. The Role of RNA Modifications and RNA-modifying Proteins in Cancer Therapy and Drug Resistance. Curr Cancer Drug Targets. 2021; 21(4):326-352. PMID: 33504307.
      Citations: 13     Fields:    Translation:HumansCells
    9. Wood S, Willbanks A, Cheng JX. RNA Cytosine Methyltransferases NSUN1 and NSUN2 Mediate the Lineage-Associated Resistance to Venetoclax in Leukemia. Blood. 2020; 136(Supplement):13-14.
    10. Stoddart A, Wang J, Fernald AA, Davis EM, Johnson CR, Hu C, Cheng JX, McNerney ME, Le Beau MM. Cytotoxic Therapy-Induced Effects on Both Hematopoietic and Marrow Stromal Cells Promotes Therapy-Related Myeloid Neoplasms. Blood Cancer Discov. 2020 07; 1(1):32-47. PMID: 32924016; PMCID: PMC7486063.
      Citations: 14     Fields:    Translation:AnimalsCells
    11. Wood S, Willbanks A, Cheng JX. RNA Cytosine Methyltransferases NSUN1 and NSUN2 Mediate the Lineage-associated Resistance to Venetoclax in Leukemia (abstract). The 62th ASH annual meeting. 2020.
    12. Wood S, Chen L, He C, Larson RA, Vardiman JW, Cheng JX. Quantitative Imaging of Drug-Selective Chromatin Topological Domains in Hematologic Malignancies: Towards Next Generation Digital Pathology and RNA Epigenomics (abstract). The 109th USCAP annual meeting. 2020.
    13. . Myelodysplastic Syndromes. In Wang, E. & Lagoo, AS (Ed) Practical Lymph Node and Bone Marrow Pathology. 2020; 24:531.
    14. . Myelodysplastic/Myeloproliferative Neoplasms. In Wang, E. & Lagoo, AS (Ed) Practical Lymph Node and Bone Marrow Pathology. 2020; 25:559.
    15. Herrou J, Willett JW, Fiebig A, Varesio LM, Czyz DM, Cheng JX, Ultee E, Briegel A, Bigelow L, Babnigg G, Kim Y, Crosson S. Periplasmic protein EipA determines envelope stress resistance and virulence in Brucella abortus. Mol Microbiol. 2019 03; 111(3):637-661. PMID: 30536925; PMCID: PMC6417958.
      Citations: 15     Fields:    Translation:AnimalsCells
    16. Hantel A, Gabster B, Cheng JX, Golomb H, Gajewski TF. Severe hemophagocytic lymphohistiocytosis in a melanoma patient treated with ipilimumab + nivolumab. J Immunother Cancer. 2018 07 16; 6(1):73. PMID: 30012206; PMCID: PMC6048909.
      Citations: 25     Fields:    Translation:Humans
    17. Cheng JX, Chen L, Li Y, Cloe A, Yue M, Wei J, Watanabe KA, Shammo JM, Anastasi J, Shen QJ, Larson RA, He C, Le Beau MM, Vardiman JW. Author Correction: RNA cytosine methylation and methyltransferases mediate chromatin organization and 5-azacytidine response and resistance in leukaemia. Nat Commun. 2018 06 06; 9(1):2286. PMID: 29875356; PMCID: PMC5989218.
      Citations: 7     Fields:    
    18. Cracolici V, Grogan RH, Sukhanova M, Cheng JX, Gurbuxani S, Cipriani NA. A Herald of Plasma Cell Myeloma: A Report of Malignant Plasma Cells Identified in Parathyroid Adenoma and a Review of Non-parathyroid Malignancies in Parathyroid Glands. Head Neck Pathol. 2018 Jun; 12(2):286-290. PMID: 29030756; PMCID: PMC5953883.
      Citations:    Fields:    Translation:HumansCells
    19. Huang PM, Hsu FM, Lin CC, Hsu CH, Cheng JC, Lee JM. Do We Need to Add Postoperative Radiotherapy in Patients Undergoing Trimodality Therapy for Esophageal Squamous Cell Carcinoma with Positive Lymph Nodes Disease? Dig Surg. 2018; 35(2):104-110. PMID: 28675905.
      Citations: 1     Fields:    Translation:Humans
    20. Stoddart A, Wang J, Hu C, Fernald AA, Davis EM, Cheng JX, Le Beau MM. Inhibition of WNT signaling in the bone marrow niche prevents the development of MDS in the Apcdel/+ MDS mouse model. Blood. 2017 06 01; 129(22):2959-2970. PMID: 28348148; PMCID: PMC5454335.
      Citations: 33     Fields:    Translation:HumansAnimalsCells
    21. Cheng JX, Chen L, Li Y, Yue M, Cloe A, Shammo JM, Larson RA, He C, Le Beau MM, Vardiman JW. RNA:m5c/Methyltransferases Mediate Chromatin Organization and 5-Azacytidine Response/Resistance in Leukemia. Blood (Supplement 1). 2017; 130:2471.
    22. Cheng JX, Chen L, Cole A, Parilla M, Le Beau MM, Larson RA, Vardiman JW. RNA/HnRNPK and BRD4/BET Mediate 5-Azacytidine (5-AZA) Action and Resistance in MDS/AML. Leukemia Research. 2017; 55:S122 .
    23. Cheng JX, Chen L, Cole A, Vardiman JA. RNA m5C methyltransferases and hnRNPK mediate disease-associated chromatin structure and drug resistance in leukemia. Cancer Res. 2017; 77:13 Suppl.
    24. Cheng JX, Chen L, Li Y. Yue M, Cloe A, Le Beau MM, He C, Larson RA, Vardiman JW. Bromodomain and Extra-Terminal Motif Proteins (BETs) Mediate 5-Azacitidine Resistance in Myeloid Leukemia through Recruitment of an Active RNA Polymerase II Complex. Platform presentation. The 63rd ASH annual meeting. 2016.
    25. Cheng JX. RNA m5C Methyltransferases and hnRNPK Mediate Lineage-Specific Chromatin Structures and Differential Responses in Leukemia Platform presentation. The Myeloid Development Symposium on the 63rd ASH annual meeting. 2016.
    26. Willett JW, Herrou J, Czyz DM, Cheng JX, Crosson S. Brucella abortus ?rpoE1 confers protective immunity against wild type challenge in a mouse model of brucellosis. Vaccine. 2016 09 30; 34(42):5073-5081. PMID: 27591954; PMCID: PMC5026968.
      Citations: 7     Fields:    Translation:AnimalsCells
    27. Cloe A, Chen L, Li Y, Liu H, Cheng JX. Identification of Specific Hnrnps As Novel Therapeutic Targets and Responsive Indicators of KPT330 (selinexor) in Leukemia. Blood. 2016; 128:1657.
    28. Aslam MN, McClintock S, Khan SP, Perone P, Allen R, Ouillette PD, Dame MK, Cheng JX, Kunkel SL, Varani J. MDI 301 suppresses myeloid leukemia cell growth in vitro and in vivo without the toxicity associated with all-trans retinoic acid therapy. Anticancer Drugs. 2015 Aug; 26(7):763-73. PMID: 26010252.
      Citations: 1     Fields:    Translation:HumansAnimalsCells
    29. Cheng JX, Anastasi J, Yue M, Shen QJ, Larson RA, Vardiman JW. Identifying distinct differentiation/lineage-specific, drug-sensitive chromatin structures and the underlying novel mutations in MDS and AML. Platform presentation. The 13th International Symposium on Myelodysplastic Syndromes. 2015.
    30. Cheng JX, Anastasi J, Vardiman JW. Distinct Chromatin Conformations of PU.1 Dictate Differential Drug Responses in Two Different Types of Leukemia Cells: Implications in Effective Epigenetic Therapy in Leukemia. Platform presentation. The USCAP 103rd Annual Meeting. 2014.
    31. Perry AM, Warnke RA, Hu Q, Gaulard P, Copie-Bergman C, Alkan S, Wang HY, Cheng JX, Bacon CM, Delabie J, Ranheim E, Kucuk C, Hu X, Weisenburger DD, Jaffe ES, Chan WC. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract. Blood. 2013 Nov 21; 122(22):3599-606. PMID: 24009234; PMCID: PMC3837508.
      Citations: 60     Fields:    Translation:HumansCells
    32. Ple-plakon PA, Demirci H, Cheng JX, Elner VM. Orbital myeloid sarcoma in an adult with acute myeloid leukemia, FAB M1, and 12p-deletion. Ophthalmic Plast Reconstr Surg. 2013 May-Jun; 29(3):e73-5. PMID: 23314098.
      Citations: 3     Fields:    Translation:HumansCells
    33. Cheng JX, Anastasi J, Watanabe K, Kleinbrink EL, Grimley E, Knibbs R, Shen QJ, Vardiman JW. Genome-wide profiling reveals epigenetic inactivation of the PU.1 pathway by histone H3 lysine 27 trimethylation in cytogenetically normal myelodysplastic syndrome. Leukemia. 2013 Jun; 27(6):1291-300. PMID: 23411464.
      Citations: 6     Fields:    Translation:HumansCells
    34. Cheng JX, Anastasi J, Shen JQ, Watanabe K, Grimley E, Kleinbrink E, Knibbs R, Roulston D, Vardiman JW. Epigenetic Mechanisms Underlying the Pathogenesis of Myelodysplastic Syndrome (MDS) and Chronic Myelomonocytic Leukemia (CMML). Modern Pathology. 2012; 25(2S):329A.
    35. Cheng JX, Anastasi J, Shen JQ, Watanabe K, Kleinbrink E, Grimley E, Knibbs R, Roulston R, Vardiman JW. Characterizing Epigenetic Patterns and Pharmacologic Responses in Myelodysplastic Neoplasms. American Journal of Clinical Pathology. 2012; 138(Suppl 2):A338-A338. View Publication.
    36. Cheng JX, Anastasi J, Vardiman JW. The 11th International Symposium on Myelodysplastic Syndromes. Profiling and Characterizing Aberrant DNA and Histone Methylations of Lineage Determining Factor Encoding Genes RUNX1, SPIB and SPI1 in Myelodysplastic Syndrome. Platform presentation. 2011.
    37. Cheng JX, Anastasi J, Shen JQ, Watanabe K, Kleinbrink E, Grimley E, Knibbs R, Roulston R, Vardiman JW. A Novel Epigenetic Mechanism in the Pathogenesis of Myelodysplastic Syndrome (MDS). Blood. 2011; 21(118):2783. View Publication.
    38. Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, Cheng JX, Murre C, Singh H, Glass CK. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010 May 28; 38(4):576-89. PMID: 20513432; PMCID: PMC2898526.
      Citations: 6181     Fields:    Translation:AnimalsCells
    39. Spooner CJ, Cheng JX, Pujadas E, Laslo P, Singh H. A recurrent network involving the transcription factors PU.1 and Gfi1 orchestrates innate and adaptive immune cell fates. Immunity. 2009 Oct 16; 31(4):576-86. PMID: 19818654; PMCID: PMC4373467.
      Citations: 94     Fields:    Translation:AnimalsCells
    40. Cheng JX, Anastasi J, Vardiman JW. Analysis of DNA Methylation and Histone H3 Trimethylation at Lysine 27 (H3K27me3) in Myelodysplastic Syndrome (MDS) with a Novel Sequential Methylated DNA Immunoprecipitation (SMeDIP) and Sequential Chromatin-Immunoprecipitation (SChIP) Technology: A Pilot Study of Refractory Cytopenia with Multilineage Dysplasia (RCMD). Modern Pathology. 2008; 21(1S):249A.
    41. Cheng JX, Tretiakova M, Gong C, Mandal S, Krausz T, Taxy JB. Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior. Mod Pathol. 2008 Jun; 21(6):647-52. PMID: 18327209.
      Citations: 69     Fields:    Translation:Humans
    42. Graham WV, Wang F, Clayburgh DR, Cheng JX, Yoon B, Wang Y, Lin A, Turner JR. Tumor necrosis factor-induced long myosin light chain kinase transcription is regulated by differentiation-dependent signaling events. Characterization of the human long myosin light chain kinase promoter. J Biol Chem. 2006 Sep 08; 281(36):26205-15. PMID: 16835238.
      Citations: 69     Fields:    Translation:HumansAnimalsCells
    43. Cheng JX, Gandolfi M, Ptashne M. Activation of the Gal1 gene of yeast by pairs of 'non-classical' activators. Curr Biol. 2004 Sep 21; 14(18):1675-9. PMID: 15380071.
      Citations: 6     Fields:    Translation:AnimalsCells
    44. Cheng JC, Peng LC, Chen YH, Huang DY, Wu JK, Jian JJ. Unique role of proximal rectal dose in late rectal complications for patients with cervical cancer undergoing high-dose-rate intracavitary brachytherapy. Int J Radiat Oncol Biol Phys. 2003 Nov 15; 57(4):1010-8. PMID: 14575832.
      Citations: 9     Fields:    Translation:HumansPHPublic Health
    45. Cheng JX, Floer M, Ononaji P, Bryant G, Ptashne M, Cheng JX, Floer M, Ononaji P, Bryant G, Ptashne M. Responses of four yeast genes to changes in the transcriptional machinery are determined by their promoters. Curr Biol. 2002 Oct 29; 12(21):1828-32. PMID: 12419182.
      Citations: 27     Fields:    Translation:Cells
    46. Cheng JX, Nevado J, Lu Z, Ptashne M, Cheng JX, Nevado J, Lu Z, Ptashne M. The TBP-inhibitory domain of TAF145 limits the effects of nonclassical transcriptional activators. Curr Biol. 2002 Jun 04; 12(11):934-7. PMID: 12062059.
      Citations: 7     Fields:    Translation:Cells
    47. Cheng X, Boyer JL, Juliano RL. Selection of peptides that functionally replace a zinc finger in the Sp1 transcription factor by using a yeast combinatorial library. Proc Natl Acad Sci U S A. 1997 Dec 09; 94(25):14120-5. PMID: 9391163; PMCID: PMC28443.
      Citations: 7     Fields:    Translation:AnimalsCells
    48. Cheng X, DeLong RK, Wickstrom E, Kligshteyn M, Demirdji SH, Caruthers MH, Juliano RL. Interactions between single-stranded DNA binding protein and oligonucleotide analogs with different backbone chemistries. J Mol Recognit. 1997 Mar-Apr; 10(2):101-7. PMID: 9376128.
      Citations: 6     Fields:    Translation:Cells
    49. . U.S. Patent: A Method for Identification and Characterization of Peptides That Recognize Specific DNA Sequences. Patent No. 5,869,250; Filing date: 1996/12/02; Grant date: 1999/02/09 https://pubchem.ncbi.nlm.nih.gov/patent/US-5869250-A. 1996. View Publication.
    50. Cheng X, Kay BK, Juliano RL. Identification of a biologically significant DNA-binding peptide motif by use of a random phage display library. Gene. 1996 May 24; 171(1):1-8. PMID: 8675015.
      Citations: 4     Fields:    Translation:Cells
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