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keywords
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RNA Epigenetics
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keywords
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RNA cytosine methylation (RNA: m5C)
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keywords
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RNA Cytosine Methyltransferase (RCMT)
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overview
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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.
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