Shalini Sharma, PhD

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Associate Professor, Basic Medical Sciences
Biography
Shalini Sharma earned her B.Sc. in Biochemistry and Microbiology from University of Bombay, India, and her Master’s in Biochemistry from Jiwaji University, India. She then obtained her Ph.D in Biochemistry from Indian Institute of Science, Bangalore working with Sunil K. Podder on ribosome-inactivating proteins. She completed her postdoctoral training in the laboratory of Douglas L. Black at the University of California, Los Angeles investigating mechanisms of pre-mRNA splicing regulation in mammals. In 2013, she joined the Departmental of Basic Medical Sciences at the University of Arizona’s College of Medicine-Phoenix. She has been a member of the Cancer Biology program since 2014 and was promoted to Associate Professor in 2019.
Cancer Focus
Somatic mutations in many proteins of the splicing machinery occur at a high frequency in myeloid malignancies including myelodysplastic syndromes (~60%), chronic myelomonocytic leukemia (~50%), and acute myeloid leukemia (~15%). Our research focuses on understanding mechanisms of splice site selection, and how splicing mutations in hematopoietic stem and progenitor cells (HSPCs) leads to a myeloid disease phenotype. We have recently identified a novel RNA binding motif, a Ubiquitin-like domain, in splicing factor 3A1 (SF3A1), and shown that MDS mutations in this domain impact RNA binding. We have also shown that mutations of another myeloid disease protein, the serine-arginine rich splicing factor 2 (SRSF2), can cause abnormal differentiation of human HSPCs.
Selected Publications
Martelly, W., B. Fellows, K. Senior, T. Marlowe, and S. Sharma, "Identification of a noncanonical RNA binding domain in the U2 snRNP protein SF3A1.", RNA, vol. 25, issue 11, pp. 1509-1521, 2019 11. PMCID: PMC6795144 PMID: 31383795
Bapat, A., N. Keita, and S. Sharma, "Pan-myeloid Differentiation of Human Cord Blood Derived CD34+ Hematopoietic Stem and Progenitor Cells.", J Vis Exp, issue 150, 2019 08 09. PMCID: PMC7046082 PMID: 31449258
Bapat, A., N. Keita, W. Martelly, P. Kang, C. Seet, J. R. Jacobsen, P. Stoilov, C. Hu, G. M. Crooks, and S. Sharma, "Myeloid Disease Mutations of Splicing Factor SRSF2 Cause G2-M Arrest and Skewed Differentiation of Human Hematopoietic Stem and Progenitor Cells.", Stem Cells, vol. 36, issue 11, pp. 1663-1675, 2018 11. PMCID: PMC6283046 PMID: 30004607
Wongpalee, S. Pop, A. Vashisht, S. Sharma, D. Chui, J. A. Wohlschlegel, and D. L. Black, "Large-scale remodeling of a repressed exon ribonucleoprotein to an exon definition complex active for splicing.", Elife, vol. 5, 2016 11 24. PMCID: PMC5122456 PMID: 27882870
Sharma, S., S. Pop Wongpalee, A. Vashisht, J. A. Wohlschlegel, and D. L. Black, "Stem-loop 4 of U1 snRNA is essential for splicing and interacts with the U2 snRNP-specific SF3A1 protein during spliceosome assembly.", Genes Dev, vol. 28, issue 22, pp. 2518-31, 2014 Nov 15. PMCID: PMC4233244 PMID: 25403181