Samrat Roy Choudhury, PhD, MSc
Arkansas Children's Hospital
College of Medicine
Cancer Research Interest
- Disease Site Focus: Leukemia/ Lymphoma, Multiple Myeloma
- Research Focus Area: Detection, Informatics, Treatment
- Type of Research: Basic
- Research Keywords: Acute Myeloid Leukemia, Epigenetics, DNA Methylation, Chromatin Biology, CRISPR , Epigenome Editing
- Research Interest Statement: Acute Myeloid Leukemia is the third most prevalent cancer among the hematological malignancies in the United States and in the state of Arkansas. AML is presented with diverse epigenetic alterations, including recurrent mutations in the epigenetic modifiers (DNMT3a, TET2, and IDH1/2) or cytolological abnormalities resulting in the epigenetic gene fusions (KMT2A fusions or AML1-ETO9). Another fascinating feature of the AML is the shift in epigenetic driver mutations across the age groups. However, exceptional transcriptional competence was observed due to the over-expression of Retionoic Acid Receptor alpha (RAR?)-PML fusion in a cohort of AML patients, irrespective of the age difference. Despite distinct epigenetic modifiers have been identified in the pediatric and adult course of the disease, similar phenotypic changes favoring the aggressive leukemogenesis have been manifested in many cases. Therefore, there remains a gap in our understanding of the epigenetic switching mechanisms of leukemic development and differentiation between different age groups. To understand the functional epigenetic landscape in AML, we will have the following aims. Aim-1: Our research focus is aimed at investigating the epigenetic regulatory mechanisms at the enhancers and promoters of the critical oncogenes and tumor suppressors that drive malignant proliferation and invasion during leukemogenesis in the AML patients, characterized with BET (BRD4), SET (KMT2A, EZH2, and NSD1) or runt (CBFA2T3) over-expressed domains. Using the multi-omics platform, we intend to identify the alterations in DNA methylation, histone modifications and transcription factor assemblies in and outside the topologically assorted domains (TAD) in AML. Aim-2: We aim to study the recurrent epigenetic mutations in AML patients in relation to their effect on the cancer cell metabolism. Suitable cells or animals will be induced with the mutant proteins to study the deleterious effects on the chromatin spread, transcriptional dysfunctions and metabolic turnover in the course hematopoiesis. CRISPR-multiplex or small molecule based drugs would be screened for their efficacy against the vulnerable targets of the mutant phenotypes.
- Email Address: SROYCHOUDHURY@UAMS.EDU
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- Roy Choudhury S, Ashby C, Zhan F, van Rhee F. Epigenetic Deregulation of Telomere-Related Genes in Newly Diagnosed Multiple Myeloma Patients. Cancers. 2021 13(24). PMID: 34944968. PMCID: PMC8699806.
- Stuckel AJ, Zeng S, Lyu Z, [et al., including Choudhury SR]. Epigenetic DNA Modifications Upregulate SPRY2 in Human Colorectal Cancers. Cells. 2021 10(10). PMID: 34685612. PMCID: PMC8534322.
- Koss B, Boerma M, Shields BD, [et al., including Choudhury SR]. Epigenetic Control of Cdkn2a.Arf Protects Tumor-Infiltrating Lymphocytes from Metabolic Exhaustion. Cancer research. 2020. PMID: 33004350. PMCID: PMC7642172.
- Choudhury SR, Ashby C, Tytarenko R, [et al.]. The functional epigenetic landscape of aberrant gene expression in molecular subgroups of newly diagnosed multiple myeloma. Journal of hematology & oncology. 2020 13(1):108. PMID: 32762714. PMCID: PMC7409490.
- Schinke C, Boyle EM, Ashby C, [et al., including Choudhury SR]. Genomic analysis of primary plasma cell leukemia reveals complex structural alterations and high-risk mutational patterns. Blood cancer journal. 2020 10(6):70. PMID: 32555163. PMCID: PMC7303180.
- Choudhury SR, Walker BA. A Rapid and Robust Protocol for Reduced Representation Bisulfite Sequencing in Multiple Myeloma. Methods in molecular biology (Clifton, N.J.). 2018 1792:179-191. PMID: 29797260.
- Choudhury SR, Ordaz J, Lo CL, [et al.]. From the Cover: Zinc oxide Nanoparticles-Induced Reactive Oxygen Species Promotes Multimodal Cyto- and Epigenetic Toxicity. Toxicological sciences : an official journal of the Society of Toxicology. 2017 156(1):261-274. PMID: 28115643.
- Lo CL, Choudhury SR, Irudayaraj J, Zhou FC. Epigenetic Editing of Ascl1 Gene in Neural Stem Cells by Optogenetics. Scientific reports. 2017 7:42047. PMID: 28181538. PMCID: PMC5299429.
- Choudhury SR, Cui Y, Narayanan A, [et al.]. Optogenetic regulation of site-specific subtelomeric DNA methylation. Oncotarget. 2016 7(31):50380-50391. PMID: 27391261. PMCID: PMC5226589.
- Choudhury SR, Cui Y, Lubecka K, [et al.]. CRISPR-dCas9 mediated TET1 targeting for selective DNA demethylation at BRCA1 promoter. Oncotarget. 2016 7(29):46545-46556. PMID: 27356740. PMCID: PMC5216816.