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Dr. Jason Cheng is a board-certified hematopathologist and cancer biologist. Dr. Cheng was trained in the following fields with the respective mentors: 1. Medicine, including medical school, surgical residence and post-graduate training in tumor pathology at Kunming Medical University and Beijing Medical University in China, respectively. 2. Molecular Pharmacology, PhD dissertation with Professor Rudy Juliano who co-discovered multidrug resistant protein/P-glycoprotein with Professor Victor Ling. 3. Molecular Biology & Gene Regulation, post-doc training with Professor Mark Ptashne, the recipient of the 1997 Lasker Basic Research Award for gene regulation. 4. Transcriptional Regulation of Hematopoiesis, research fellow with Professor Harinder Singh, a former HHMI investigator at UChicago. 5. Diagnostic Hematology and Hematopathology, clinical fellowship with Professor James Vardiman, a leading expert in Diagnostic Hematopathology. As a pathologist board-certified in Anatomic Pathology and Clinical Pathology (AP/CP) as well as in Hematology/Hematopathology, Dr. Cheng focuses on hematologic diseases, particularly 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. 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 focusing on the role of RNA epigenetics, more specifically RNA:m5C and its writers NSUN1 (NOP2/NOL1) and NSUN2, in hematological malignancies and development of novel RNA epigenetics-driven diagnostics and therapeutics to predict and overcome multidrug resistance in leukemia and cancer. Dr. Cheng’s lab has been collaborating with Professor Rick Stevens, the Associate Laboratory Director for the Computing, Environment and Life Sciences (CELS) at the Argonne National Laboratory (ANL) for artificial intelligence (AI)-assisted drug discovery. By leveraging the Argonne AI supercomputer and their NSUN1/2-targeting functional technologies, the laboratories of Dr. Stevens and Dr. Cheng designed and screened 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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