Contact Information
Biography
Dr. Mihailescu is the department chair and professor of the department of Chemistry and Biochemistry. She’s a distinguished Postdoctoral Research Associate with a specialization in biotechnology and molecular biology. She conducted pioneering research at the Center for Advanced Research in Biotechnology/NIST in Rockville, MD. The research primarily focused on Nuclear Magnetic Resonance Spectroscopy Studies of the HIV-1 Dimer Initiation Site Kissing Complex and its Interactions with the Nucleocapsid 7 Protein.
With a Ph.D. in Molecular Biology & Biochemistry from Wesleyan University, Dr. Mihailescu's doctoral dissertation, titled "Structural Energetics in Human Hemoglobin: A Nuclear Magnetic Resonance Spectroscopy Investigation," delved into the intricacies of human hemoglobin, showcasing advanced expertise in spectroscopic techniques. Additionally, Dr. Mihailescu holds an M.S./B.S. in Biophysics/Physics from the University of Bucharest, Romania. Her research is characterized by a comprehensive background and a proven track record of impactful contributions to molecular biology and biophysics.
Education
- B.S., M.S. University of Bucharest
- Ph.D., Wesleyan University, CT
- Post Doctoral Fellow, Center for Advanced Research in Biotechnology
Research Interests
Fragile X Syndrome (FXS) Molecular Basis:
- Investigated the genetic underpinnings of Fragile X Syndrome, focusing on the CGG trinucleotide repeat expansion in the 5' untranslated region (UTR) of the fragile X mental retardation-1 (Fmr1) gene.
- Explored the correlation between CGG repeat length and the manifestation of FXS symptoms, contributing to our understanding of the transition from the general population's 6-54 repeats to over 200 in the full mutation, resulting in Fmr1 gene silencing.
Structural and Functional Characterization of FMRP:
- Conducted in-depth analysis of Fragile X Mental Retardation Protein (FMRP), emphasizing its RNA-binding motifs (two K Homology domains and an RGG-rich box) and posttranslational modifications, including phosphorylation and arginine methylation.
- Investigated alternative splicing events within the Fmr1 gene, particularly focusing on exons 12 and 14, and the acceptor sites in exons 15 and 17.
RNA Recognition Motifs and G Quadruplex Structures:
- Examined the RNA recognition motifs of FMRP, highlighting the proposed G quadruplex (GQ) structure as a specific motif with high affinity and specificity for the FMRP RGG box.
- Validated the existence of GQ structures in various FMRP neuronal mRNA targets, elucidating the thermodynamics of their interactions with FMRP.
FMRP in Translation Regulation:
- Explored the role of FMRP in the transport and translation regulation of specific neuronal mRNA targets.
- Investigated the interaction between FMRP and the microRNA (miRNA)-guided RNA induced silencing complex (RISC) in repressing translation, with a focus on miR125a-loaded RISC and its association with the post-synaptic density 95 (PSD-95) mRNA.
Biochemical and Biophysical Approaches:
- Employed biochemical and biophysical methods to elucidate the molecular mechanisms underlying FMRP's interaction with the miRNA pathway and its translation regulator function.
- Investigated how alternative splicing and posttranslational modifications of FMRP might influence its overall protein function.
Profile Information
Publications and Awards
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Caleb J. Frye, Morgan Shine, Joseph A. Makowski, Adam H. Kensinger, Caylee L. Cunningham, Ella J. Milback, Jeffrey D. Evanseck, Patrick E. Lackey, Mihaela Rita Mihailescu, "Structural, Dynamical, and Entropic Differences between SARS-CoV and SARS-CoV-2 s2m Elements Using Molecular Dynamics Simulations" ACS Phys. Chem Au 2023, 3, 1, 30–43, October 2022.
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Caleb J. Frye, Morgan Shine, Joseph A. Makowski, Adam H. Kensinger, Caylee L. Cunningham, Ella J. Milback, Jeffrey D. Evanseck, Patrick E. Lackey, Mihaela Rita Mihailescu, Bioinformatics analysis of the s2m mutations within the SARS-CoV-2 Omicron lineages. Journal of Medical Virology, Volume 95, Number 1, January 2023.
- Highly conserved s2m element of SARS-CoV-2 dimerizes via a kissing complex and interacts with host miRNA-1307-3p. Nucleic Acids Res. 2022 Jan 25;50(2):1017-1032. doi: 10.1093/nar/gkab1226. PMID: 34908151 Free PMC article.
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Imperatore J.A., Then M.L., McDougal K.B. & Mihailescu M.R., Characterization of a G-quadruplex structure in pre-miRNA-1229 and in its Alzheimer's disease-associated variant rs2291418: implications for miRNA-1229 maturation. Int J Mol Sci. 2020 Jan 24;21(3):767.
doi:10.3390/ijms21030767 -
Imperatore J.A., McAninch D.S., Valdez-Sinon, AN, Bassell, G.J. & Mihailescu, M.R., FUS Recognizes G Quadruplex Structures Within Neuronal mRNAs. Front Mol Biosci 2020 Feb 7;7:6. doi: 10.3389/fmolb.2020.00006. eCollection 2020. (invited article)
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DeMarco B., Stefanovic S., Williams A., Moss, K.R., Anderson B.R., Bassell G.J. & Mihailescu M.R., FMRP-G quadruplex mRNA- miR-125a interactions: Implications for miR-125a-mediated translation regulation of PSD-95 mRNA. PLoS One 2019 May 21;14(5): e0217275. doi: 10.1371/journal.pone.0217275. eCollection 2019.
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McAninch, D.S., Heinaman A.M., Lang, C.N., Moss, K.R., Bassell, G.J., Mihailescu, M.R. & Evans, T.L., Fragile X mental retardation protein recognizes a G quadruplex structure within the survival motor neuron domain containing 1 mRNA 5'-UTR. Mol. Biosyst. 2017, 13(8):1448-1457.
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Bartley, C.M., O'Keefe, R.A., Blice-Baum, A., Mihailescu, M.R., Miyares, L., Karaca, E. & Bordey, A., Mammalian FMRP S499 is phosphorylated by CK2 and promotes secondary phosphorylation of FMRP, eNeuro 2016 3(6). pii: ENEURO.0092-16.2016. eCollection 2016 Nov-Dec.
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Williams, K.R., McAninch, D.S., Stefanovic, S., Xing, L., Allen, M., Li, W., Feng, Y., Mihailescu, M.R. & Bassell, G.J., hnRNP-Q1 represses nascent axon growth in cortical neurons by inhibiting Gap-43 mRNA, Mol. Biol. Cell. 2016, 27(3):518-534. doi: 10.1091/mbc.E15-07-0504.
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Mihailescu, R., Gene expression regulation: lessons from noncoding RNAs, RNA 2015, 21(4): 695-696. (invited article).
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Stefanovic S., DeMarco, B.A., Underwood, A., Williams, K.R., Bassell, G.J. & Mihailescu, M.R., Fragile X mental retardation protein interactions with a G quadruplex structure in the 3'-untranslated region of NR2B mRNA, Mol Biosyst. 2015 11(12):3222-30. doi: 10.1039/c5mb00423c. (featured on the cover of the Molecular Biosystems Journal)
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Stefanovic, S., Bassell G.J. & Mihailescu, M.R., G quadruplex RNA structures in PSD -95 mRNA: potential regulators of miR-125a seed binding site accessibility, RNA. 2015 21(1):48-60. doi: 10.1261/rna.046722.114.
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Zhang, Y., Gaetano, C., Williams, K.R., Bassell G.J. & Mihailescu, M.R., FMRP interacts with G quadruplex structures in the 3'-UTR of its dendritic target Shank1 mRNA, RNA Biol. 2014;11(11):1364-74. doi: 10.1080/15476286.2014.996464.
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Blice-Baum AC. & Mihailescu M.R., Biophysical characterization of G-quadruplex forming FMR1 mRNA and of its interactions with different fragile X mental retardation protein isoforms. RNA. 2014, 20(1):103-14. Epub 2013 Nov 18.
- Presidential Award for Excellence in Scholarship, Duquesne University
- Bayer School of Natural and Environmental Sciences Excellencein Scholarship Award, Duquesne University
- Bayer School of Natural and Environmental Sciences Excellence in Scholarship Award, Duquesne University
- Ruth L. Kirschstein National Research Service Award, National Institutes of Health/ National Institute of Allergy and Infectious Diseases
- Teacher of the Year Award by Duquesne University’s Chapter of Omicron Delta Kappa National Leadership Honor Society
- Bayer School of Natural and Environmental Sciences Excellence in Teaching Award, Duquesne University
- Competitive Travel Award to the XXth International Conference of Magnetic Resonance in Biological Systems, Toronto, Canada
- Peterson Fellowship for Graduate Studies in Biochemistry, Wesleyan University
- Fellowship to the "Biophysics of Proton and Ion Transport"-International Summer School, Brasov, Romania