Mohammad Alinoor Rahman, PhD, MS

Research Program: Cancer Biology Faculty Rank: Assistant Professor Campus: University of Arkansas for Medical Sciences College: College of Medicine Department: Biochemistry & Molecular Biology

Cancer Research Interest

• Disease Site Focus: Hematologic Malignancies, Leukemia/ Lymphoma, Breast, Melanoma
• Research Focus Area: Carcinogenesis, Treatment, Informatics
• Type of Research: Basic, Translational
• Research Interest Statement: RNA processing misregulation has been highlighted as a critical driver of tumorigenesis through emerging discoveries in the past decade. Alternative splicing (AS) and nonsense-mediated mRNA decay (NMD) are two important RNA processing mechanisms in controlling gene expression, and their misregulation often leads to malignancy. Although therapeutic approaches to modulate AS/NMD in several genetic diseases are reaching the clinic, this is an under-explored area in cancer. My research is focused on bridging the gap between RNA biology and cancer research. My work distinguishes itself by the systematic use of diseaserelevant model systems to elucidate the mechanisms of RNA processing defects in cancer. Recent efforts to profile AS/NMD in human tumors have revealed that many of the changes in AS/NMD are cell-typespecific. Therefore, studies investigating the underlying mechanisms in disease-relevant model systems will provide invaluable insights into the role of RNA biology in cancer, elucidate pathological phenomena, and aid in developing novel therapeutic strategies. My recent works (Rahman et al., Genes Dev 2020; Rahman et al., Cell 2020; Yoshimi et al., Nature 2019) identified a critical link between AS-coupled-NMD (ASNMD) and hematologic malignancies. My current research explores the molecular basis of aberrant regulation in targeted AS-NMD genes in myelodysplastic syndromes and leukemia and the development of targeted tools (such as antisense therapy) to modulate aberrant AS-NMD as a therapeutic approach. I am also interested in exploring the role of AS-NMD in the pathogenesis of different solid tumors, including melanoma and breast tumors. My research will broaden the basic understanding of AS and NMD regulation in the post-transcriptional RNA processing pathway in normal physiology and aberrant regulation in cancer. In addition, identifying oncogenic targets should lead to the discovery of novel cancer biomarkers and aid in developing targeted cancer therapies.

Contact Information

• Email Address: MARAHMAN@UAMS.EDU
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Active Grants

• Edward P. Evans Foundation – EYIA 2020
  “Aberrant Splicing and NMD in MDS”
  Principal Investigator
  07/01/22 – 06/30/23

Publications

• Nagar P, Islam MR, Rahman MA. Nonsense-Mediated mRNA Decay as a Mediator of Tumorigenesis. Genes. 2023 14(2). PMID: 36833284. PMCID: PMC9956241.
• Gao Y, Lin KT, Jiang T, [et al., including Rahman MA]. Systematic characterization of short intronic splicing-regulatory elements in SMN2 pre-mRNA. Nucleic acids research. 2022. PMID: 35018432. PMCID: PMC8789036.
• Rahman MA, Nasrin F, Bhattacharjee S, Nandi S. Hallmarks of Splicing Defects in Cancer: Clinical Applications in the Era of Personalized Medicine. Cancers. 2020 12(6). PMID: 32481522. PMCID: PMC7352608.
• Rahman MA, Lin KT, Bradley RK, [et al.]. Recurrent SRSF2 mutations in MDS affect both splicing and NMD. Genes & development. 2020 34(5-6):413-427. PMID: 32001512. PMCID: PMC7050488.
• Rahman MA, Krainer AR, Abdel-Wahab O. SnapShot: Splicing Alterations in Cancer. Cell. 2020 180(1):208-208.e1. PMID: 31951519. PMCID: PMC7291876.
• Yoshimi A, Lin KT, Wiseman DH, [et al., including Rahman MA]. Coordinated alterations in RNA splicing and epigenetic regulation drive leukaemogenesis. Nature. 2019 574(7777):273-277. PMID: 31578525. PMCID: PMC6858560.
• Feng H, Bao S, Rahman MA, [et al.]. Modeling RNA-Binding Protein Specificity In Vivo by Precisely Registering Protein-RNA Crosslink Sites. Molecular cell. 2019 74(6):1189-1204.e6. PMID: 31226278. PMCID: PMC6676488.
• Aznarez I, Nomakuchi TT, Tetenbaum-Novatt J, [et al., including Rahman MA]. Mechanism of Nonsense-Mediated mRNA Decay Stimulation by Splicing Factor SRSF1. Cell reports. 2018 23(7):2186-2198. PMID: 29768215. PMCID: PMC5999336.
• Ahsan KB, Masuda A, Rahman MA, [et al.]. SRSF1 suppresses selection of intron-distal 5' splice site of DOK7 intron 4 to generate functional full-length Dok-7 protein. Scientific reports. 2017 7(1):10446. PMID: 28874828. PMCID: PMC5585400.
• Ohno K, Rahman MA, Nazim M, [et al.]. Splicing regulation and dysregulation of cholinergic genes expressed at the neuromuscular junction. Journal of neurochemistry. 2017 142 Suppl 2:64-72. PMID: 28072465.
• Nazim M, Masuda A, Rahman MA, [et al.]. Competitive regulation of alternative splicing and alternative polyadenylation by hnRNP H and CstF64 determines acetylcholinesterase isoforms. Nucleic acids research. 2017 45(3):1455-1468. PMID: 28180311. PMCID: PMC5388418.
• Shibata A, Okuno T, Rahman MA, [et al.]. IntSplice: prediction of the splicing consequences of intronic single-nucleotide variations in the human genome. Journal of human genetics. 2016 61(7):633-40. PMID: 27009626.