As a physician-scientist I am interested in understanding the genetic and molecular basis of splicing factor gene mutations in clonal hematopoiesis and myeloid malignancies, such as myelodysplastic syndromes (MDS). My postdoctoral work demonstrated that mutations in the U2AF1 splicing factor gene provide an ideal model for these studies as they occur at one of two hotspot codons (S34 and Q157) in separate zinc finger domains, and each of these mutations are associated with different clinical features, outcomes, alternative splicing, and co-occurring gene mutations in MDS patients. Complimentary experiments using U2af1(S34F/+) and U2af1(Q157R/+) small animal models support these observations and have also revealed differential activation of several key signaling pathways.
The goal of our lab's research program is focused on answering the following questions:
(1) Why are splicing factor mutations highly enriched in clonal myeloid malignancies (e.g., MDS) compared to other types of cancer?
(2) What are the individual and shared mechanisms by which different splicing factor mutations induce MDS?
(3) What are the dynamics facilitating acquisition of additional mutations in the context of splicing factor mutant disease?
Wadugu BA, Nonavinkere Srivatsan S, Heard A, Alberti MO, Ndonwi M, Liu J, Grieb S, Bradley J, Shao J, Ahmed T, Shirai CL, Khanna A, Fei DL, Miller CA, Graubert TA, Walter MJ. U2af1 is a haplo-essential gene required for hematopoietic cancer cell survival in mice. J Clin Invest. 2021 Nov 1;131(21). PubMed PMID: 34546980
Kim SP, Srivatsan SN, Chavez M, Shirai CL, White BS, Ahmed T, Alberti MO, Shao J, Nunley R, White LS, Bednarski J, Pehrson JR, Walter MJ. Mutant U2AF1-induced alternative splicing of H2afy (macroH2A1) regulates B-lymphopoiesis in mice. Cell Rep. 2021 Aug 31;36(9):109626. PubMed PMID: 34469727
Mullegama SV, Alberti MO, Au C, Li Y, Toy T, Tomasian V, Xian RR. Nucleic Acid Extraction from Human Biological Samples. Methods Mol Biol. 2019;1897:359-383. PubMed PMID: 30539458
Alberti MO, Srivatsan SN, Shao J, McNulty SN, Chang GS, Miller CA, Dunlap JB, Yang F, Press RD, Gao Q, Ding L, Heusel JW, Duncavage EJ, Walter MJ. Discriminating a common somatic ASXL1 mutation (c.1934dup; p.G646Wfs*12) from artifact in myeloid malignancies using NGS. Leukemia. 2018 Aug;32(8):1874-1878. PubMed PMID: 29959414
Albeiroti S, Alberti MO, Buggs V, Swartz G, Butch AW, Drees JC, Kelly KA. Evaluation of 2 Batched Pretreatment Systems for the Measurement of Whole Blood Tacrolimus on the ARCHITECT Immunoassay Analyzer. Lab Med. 2016 Nov;47(4):268-274. PubMed PMID: 27474776
Alberti MO, Hindler JA, Humphries RM. Erratum for Alberti et al., Antimicrobial Susceptibilities of Abiotrophia defectiva, Granulicatella adiacens, and Granulicatella elegans. Antimicrob Agents Chemother. 2016 Jun;60(6):3868. PubMed PMID: 27217443
Alberti MO, Hindler JA, Humphries RM. Performance of Etest for Antimicrobial Susceptibility Testing of Abiotrophia defectiva and Granulicatella Species. J Clin Microbiol. 2016 Aug;54(8):2194-6. PubMed PMID: 27280419
King JK, Ung NM, Paing MH, Contreras JR, Alberti MO, Fernando TR, Zhang K, Pellegrini M, Rao DS. Regulation of Marginal Zone B-Cell Differentiation by MicroRNA-146a. Front Immunol. 2016;7:670. PubMed PMID: 28138326
Roth JC, Alberti MO, Ismail M, Lingas KT, Reese JS, Gerson SL. MGMT enrichment and second gene co-expression in hematopoietic progenitor cells using separate or dual-gene lentiviral vectors. Virus Res. 2015 Jan 22;196:170-80. PubMed PMID: 25479595
Alberti MO, Drake TA, Song L. The pH of chemistry assays plays an important role in monoclonal immunoglobulin interferences. Pract Lab Med. 2015 Dec 1;3:8-16. PubMed PMID: 28932804
Alberti MO, Jones JJ, Miglietta R, Ding H, Bakshi RK, Edmonds TG, Kappes JC, Ochsenbauer C. Optimized Replicating Renilla Luciferase Reporter HIV-1 Utilizing Novel Internal Ribosome Entry Site Elements for Native Nef Expression and Function. AIDS Res Hum Retroviruses. 2015 Dec;31(12):1278-96. PubMed PMID: 26101895
Alberti MO, Fukuchi AM, Kelly KA. Influence of serum separator tubes on mycophenolic acid concentrations determined by HPLC. Ther Drug Monit. 2014 Oct;36(5):686-7. PubMed PMID: 24718269
Woo JS, Alberti MO, Tirado CA. Childhood B-acute lymphoblastic leukemia: a genetic update. Exp Hematol Oncol. 2014;3:16. PubMed PMID: 24949228
Alberti MO, Deshane JS, Chaplin DD, Pereboeva L, Curiel DT, Roth JC. A myeloid cell-binding adenovirus efficiently targets gene transfer to the lung and escapes liver tropism. Gene Ther. 2013 Jul;20(7):733-41. PubMed PMID: 23171918
Alberti MO, Roth JC, Ismail M, Tsuruta Y, Abraham E, Pereboeva L, Gerson SL, Curiel DT. Derivation of a myeloid cell-binding adenovirus for gene therapy of inflammation. PLoS One. 2012;7(5):e37812. PubMed PMID: 22624065