Samrat Roy Choudhury, PhD, MSc

Research Program: Cancer Biology Faculty Rank: Assistant Professor Campus: Arkansas Children's Hospital College: College of Medicine Department: Pediatrics

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 (RARα)-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.

Contact Information

• Email Address: SROYCHOUDHURY@UAMS.EDU
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Publications

• Choudhury SR, Byrum SD, Blossom SJ. Trichloroethylene metabolite modulates DNA methylation-dependent gene expression in Th1 polarized CD4+ T cells from autoimmune-prone mice. Toxicological sciences : an official journal of the Society of Toxicology. 2024. PMID: 38518092.
• Sabol HM, Ashby C, Adhikari M, [et al., including Choudhury SR]. A NOTCH3-CXCL12-driven myeloma-tumor niche signaling axis promotes chemoresistance in multiple myeloma. Haematologica. 2024. PMID: 38385272.
• Frett B, Stephens KE, Koss B, [et al., including Roy Choudhury S]. Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia. Cancer science. 2024. PMID: 38226414. PMCID: PMC10920984.
• Choudhury S, Heflin B, Taylor E, [et al.]. CRISPR/dCas9-KRAB-Mediated Suppression of S100b Restores p53-Mediated Apoptosis in Melanoma Cells. Cells. 2023 12(5). PMID: 36899866. PMCID: PMC10000373.
• Choudhury S, Byrum SD, Alkam D, [et al.]. Expression of integrin β-7 is epigenetically enhanced in multiple myeloma subgroups with high-risk cytogenetics. Clinical epigenetics. 2023 15(1):18. PMID: 36737807. PMCID: PMC9898982.
• 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.