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Jason X. Cheng

Associate Professor
jxcheng@uchicago.edu
Research Summary
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 and are involved in essential bioprocesses, including chromatin organization, transcription and translation, as well as cell differentiation, aging and human disease development (Willbanks A, Wood S, Cheng JX. Genes. 2021). However, due to a lack of appropriate technologies and animal models, the pathophysiological role and the clinical potential of RNA:m5C, NSUN1 (NOP2/NOL1) and NSUN2 remain largely unexplored. 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.
Keywords
Hematology, Hematopathology, Myelodysplastic syndromes (MDS), Myeloproliferative neoplasms (MPN), Acute myeloid leukemia (AML), Hematopoiesis, Genetic and Epigenetic, RNA Epigenetics, RNA cytosine methylation (RNA: m5C), RNA Cytosine Methyltransferase (RCMT), NSUN1 (NOP2/NOL1), NSUN2, Chromatin structure, Drug resistance
Education
  • University of Chicago, Chicago, Clinical Fellowship mentored by Dr. James Vardiman Hematopathology 06/2010
  • University of Chicago, Chicago, Residency Anatomic and Clinical Pathology (AP/CP) 07/2008
  • Memorial Sloan Kettering Cancer Center, New York, Post-doc in Dr. Mark Ptashne Lab Molecular Biology & Yeast Genetics 06/2004
  • University of North Carolina, Chapel Hill, Post-doc in Dr. Rudy Juliano Lab Pharmacology 08/1999
  • University of North Carolina, Chapel Hill, PhD mentored by Dr. Rudy Juliano Pharmacology 08/1997
  • University of North Carolina, Chapel Hill, Research Fellow Pathology 08/1993
  • People’s Hospital of Beijing Medical University, Beijing, Instructor Pathology 08/1992
  • Beijing Medical University, Beijing, Master of Science (MS) mentored by Dr. Guo Quanxin Pathology 08/1990
  • Yunnan Red Cross Hospital, Kunming, Residency Surgery 08/1987
  • Kunming Medical University, Kunming, Bachelor (MD equivalent) Medicine 08/1983
Biosciences Graduate Program Association
Awards & Honors
  • 2007 - The Robert E. Priest Fellowship University of Chicago
  • 2007 - The winner of Chicago Pathology Society Resident Research Awards Chicago Pathology Society
  • 2008 - The Pathologist-in-Training Award Society for Hematopathology/United States and Canadian Academy of Pathology (USACP)
  • 2008 - The Paul E. Strandjord Young Investigator Award Academy of Clinical Physicians and Scientists
  • 2008 - The USCAP Best Abstract Award The International Association of Chinese Pathologists
  • 2012 - The Best Oral Platform Presentation The American Society for Clinical Pathology
  • 2013 - The American Cancer Society (ACS-IRG) Award University of Chicago
  • 2014 - The American Cancer Society (ACS-IRG) University of Chicago
  • 2014 - The Young Investigator Award Cancer Research Foundation
  • 2016 - The Swim Across America: Rush University/UChicago ITM Pilot Award Swim Across America.org
  • 2019 - The Michael Reese Bench-to-Bedside Translational Science Award Michael Reese Foundation
  • 2019 - The Taub Medical foundation for MDS program Awards The Henry and Marilyn Taub Foundation
Publications

  1. 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 Mar 21. View in: PubMed

  2. 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). View in: PubMed

  3. 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. View in: PubMed

  4. 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. View in: PubMed

  5. 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. View in: PubMed

  6. 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. View in: PubMed

  7. 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. View in: PubMed

  8. 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. View in: PubMed

  9. 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. View in: PubMed

  10. 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. View in: PubMed

  11. 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. View in: PubMed

  12. 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. View in: PubMed

  13. 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. View in: PubMed

  14. 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. View in: PubMed

  15. 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. View in: PubMed

  16. 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. View in: PubMed

  17. 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. View in: PubMed

  18. 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. View in: PubMed

  19. 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. View in: PubMed

  20. 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. View in: PubMed

  21. 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. View in: PubMed

  22. 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. View in: PubMed

  23. 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. View in: PubMed

  24. 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. View in: PubMed

  25. 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. View in: PubMed

  26. 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.::::

  27. 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.::::

  28. 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.::::

  29. 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.::::

  30. 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 .::::

  31. 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.::::

  32. 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.::::

  33. Cheng X, Juliano RL. 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.::::

  34. 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.::::

  35. 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.::::

  36. 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.::::

  37. 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. 2012; 138(S2):A338-A338.::::

  38. 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.::::

  39. 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.::::

  40. 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.::::

  41. Jason X. Cheng and James W. Vardiman. Myelodysplastic Syndromes. In Wang, E. & Lagoo, AS (Ed) Practical Lymph Node and Bone Marrow Pathology. 2020; 24:531.::::

  42. 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.::::

  43. 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.::::

  44. Jason Cheng and James W. Vardiman. Myelodysplastic/Myeloproliferative Neoplasms. In Wang, E. & Lagoo, AS (Ed) Practical Lymph Node and Bone Marrow Pathology. 2020; 25:559.::::
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