Welcome to Alexandrov lab
Identification of Disease-Associated Human RNA Pathways
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We are state-of-the-art-equipped lab in the Clemson Institute for Human Genetics. We use forward genetics and biochemistry to identify and study disease-associated human pathways of RNA biogenesis, regulation, and surveillance.
We extensively use high-throughput methods that employ CRISPR-based mutagenesis of the human genome and fluorescence-activated cell sorting (FACS). The RNA pathways we are focusing on play critical roles in (a) cancer and (b) genetic diseases that arise from mutations resulting in a premature termination codon. Among cancer-associated human RNA pathways, we are focusing on those regulating human nuclear long non-coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1). |
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Publications:
Che R., Mirani B., Panah M., Chen X., Luo H., and Alexandrov A. (2025) Identification of RMP24 and RMP64, Human Ribonuclease MRP-Specific Protein Components. Cell Reports https://doi.org/10.1016/j.celrep.2025.115752
Che R., Panah M., Mirani B., Knowles K., Ostapovich A., Majumdar D., Chen X., DeSimone J., White W., Noonan M., Luo H., and Alexandrov, A. (2025) Identification of Human Pathways Acting on Nuclear Non-Coding RNAs Using the Mirror Forward Genetic Approach. Nature Communications https://doi.org/10.1038/s41467-025-59998-3
Alexandrov, A., Che, R., Mirani, B., Panah, M. (2024) Bacteria-Free Approach for Expressing Nucleic Acids and Proteins in Eukaryotic Cells. U.S. Patent Application US20250163437A1. patents.google.com/patent/US20250163437A1/
Alexandrov, A., Steitz, J.A. (2021) Fluorescence Amplification Method for Forward Genetic Discovery of Factors in Human mRNA Degradation. U.S. Patent US11060153B2. patents.google.com/patent/US11060153B2/
Alexandrov, A., Shu M.D., Steitz J.A. (2017) Fluorescence Amplification Method for Forward Genetic Discovery of Factors in Human mRNA Degradation. Molecular Cell 65(1):191-201. PMC5301997. www.cell.com/molecular-cell/fulltext/S1097-2765(16)30777-8
Herbert K.M., Pimienta G., DeGregorio S.J., Alexandrov, A., Steitz J.A. (2013) Phosphorylation of DGCR8 increases its intracellular stability and induces a progrowth miRNA profile. Cell Reports 5(4):1070-81. PMID: 24239349.
Alexandrov, A., Colognori D., Shu M.D., Steitz J.A. (2012) Human spliceosomal protein CWC22 plays a role in coupling splicing to exon junction complex deposition and nonsense-mediated decay. Proc Natl Acad Sci U S A. 109(52): 21313-18. PMC3535618.
Alexandrov, A., Colognori D., and Steitz J.A., (2011) Human eIF4AIII interacts with an eIF4G-like partner, NOM1, revealing an evolutionarily conserved function outside the exon junction complex. Genes & Dev. 25: 1078-90. PMC3093123.
Quartley E., Alexandrov, A., Mikucki M., Buckner F.S., Hol W.G., DeTitta G.T., Phizicky E.M., Grayhack E.J. (2009) Heterologous expression of L. major proteins in S. cerevisiae: a test of solubility, purity, and gene recoding. J. Struct. Funct. Genomics. 10(3):233-47. PMID:19701618.
Alexandrov, A., Chernyakov I., Gu W., Hiley S., Hughes T.R., Grayhack E.J., Phizicky E.M. (2006) Rapid tRNA decay can result from lack of non-essential modifications. Molecular Cell 21(1): 87-96. PMID: 16387656. [preview in: Engelke D.R., Hopper A.K. (2006) Modified view of tRNA: stability amid sequence diversity. Molecular Cell 21(2), 144-5. PMID: 16427003.]
Ma X., Yang C., Alexandrov, A., Grayhack E.J., Behm-Ansmant I., Yu Y.T. (2005) Pseudouridylation of yeast U2 snRNA is catalyzed by either an RNA-guided or RNA-independent mechanism. EMBO J. 24(13): 2403-13. PMC1173158.
Cartlidge R.A., Knebel A., Peggie M., Alexandrov, A., Phizicky E.M., Cohen P. (2005) The tRNA methylase METTL1 is phosphorylated and inactivated by PKB and RSK in vitro and in cells. EMBO J. 24(9): 1696–1705. PMC1142581.
Alexandrov, A., Grayhack, E. J., Phizicky, E. M. (2005) tRNA m7G methyltransferase Trm8p/Trm82p: evidence linking activity to a growth phenotype and implicating Trm82p in maintaining levels of active Trm8p. RNA 11:821-830. PMC1370766.
Alexandrov, A., Vignali M., LaCount D.J., Quartley E., de Vries C., De Rosa D., Babulski J., Mitchell S.F., Schoenfeld L.W., Fields S., Hol W.G., Dumont M.E., Phizicky E.M., Grayhack E.J. (2004) A facile method for high-throughput co-expression of protein pairs. Mol. Cell. Proteomics 3: 934-938. PMID:15240823.
Eliseev R., Alexandrov, A., Gunter T. (2004) High-yield expression and purification of p18 form of Bax as an MBP-fusion protein. Protein Expr Purif. 35(2):206-9. PMID: 15135394.
Gunter T.E., Miller L.M., Gavin C.E., Eliseev R., Salter J., Buntinas L., Alexandrov, A., Hammond S., Gunter K.K. (2004) Determination of the oxidation states of manganese in brain, liver, and heart mitochondria. J. Neurochem. 88(2):266-80. PMID: 14690515.
Dutta K., Engler F.A., Cotton L., Alexandrov, A., Bedi G.S., Colquhoun J., Pascal S.M. (2003) Stabilization of a pH-sensitive apoptosis-linked coiled coil through single point mutations. Protein Sci. 12(2):257-65. PMID: 12538889.
Alexandrov, A., Martzen MR., and Phizicky E.M. (2002) Two proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA. RNA 8:1253-1266. PMC1370335.
Dutta K., Cox C.J., Alexandrov, A., Huang H., Basavappa R., Pascal S.M. (2002) Sequence-specific chemical shift assignment and chemical shift indexing of murine apo-Mts1. J. Biomol NMR. 22(2):181-2. PMID: 11883779.
Dutta K., Alexandrov, A., Huang H., Pascal SM. (2001) pH-induced folding of an apoptotic coiled coil. Protein Sci. 10(12):2531-40. PMID: 11714921.
Huang H., Alexandrov, A., Chen X., Barnes T.W. 3rd, Zhang H., Dutta K., Pascal S.M. (2001) Structure of an RNA hairpin from HRV-14. Biochemistry. 40(27):8055-64. PMID: 11434774.
Alexandrov, A., Dutta K., Pascal S.M. (2001) MBP fusion protein with a viral protease cleavage site: one-step cleavage/purification of insoluble proteins. Biotechniques, 30(6):1194-1198. PMID: 11414203.
Che R., Panah M., Mirani B., Knowles K., Ostapovich A., Majumdar D., Chen X., DeSimone J., White W., Noonan M., Luo H., and Alexandrov, A. (2025) Identification of Human Pathways Acting on Nuclear Non-Coding RNAs Using the Mirror Forward Genetic Approach. Nature Communications https://doi.org/10.1038/s41467-025-59998-3
Alexandrov, A., Che, R., Mirani, B., Panah, M. (2024) Bacteria-Free Approach for Expressing Nucleic Acids and Proteins in Eukaryotic Cells. U.S. Patent Application US20250163437A1. patents.google.com/patent/US20250163437A1/
Alexandrov, A., Steitz, J.A. (2021) Fluorescence Amplification Method for Forward Genetic Discovery of Factors in Human mRNA Degradation. U.S. Patent US11060153B2. patents.google.com/patent/US11060153B2/
Alexandrov, A., Shu M.D., Steitz J.A. (2017) Fluorescence Amplification Method for Forward Genetic Discovery of Factors in Human mRNA Degradation. Molecular Cell 65(1):191-201. PMC5301997. www.cell.com/molecular-cell/fulltext/S1097-2765(16)30777-8
Herbert K.M., Pimienta G., DeGregorio S.J., Alexandrov, A., Steitz J.A. (2013) Phosphorylation of DGCR8 increases its intracellular stability and induces a progrowth miRNA profile. Cell Reports 5(4):1070-81. PMID: 24239349.
Alexandrov, A., Colognori D., Shu M.D., Steitz J.A. (2012) Human spliceosomal protein CWC22 plays a role in coupling splicing to exon junction complex deposition and nonsense-mediated decay. Proc Natl Acad Sci U S A. 109(52): 21313-18. PMC3535618.
Alexandrov, A., Colognori D., and Steitz J.A., (2011) Human eIF4AIII interacts with an eIF4G-like partner, NOM1, revealing an evolutionarily conserved function outside the exon junction complex. Genes & Dev. 25: 1078-90. PMC3093123.
Quartley E., Alexandrov, A., Mikucki M., Buckner F.S., Hol W.G., DeTitta G.T., Phizicky E.M., Grayhack E.J. (2009) Heterologous expression of L. major proteins in S. cerevisiae: a test of solubility, purity, and gene recoding. J. Struct. Funct. Genomics. 10(3):233-47. PMID:19701618.
Alexandrov, A., Chernyakov I., Gu W., Hiley S., Hughes T.R., Grayhack E.J., Phizicky E.M. (2006) Rapid tRNA decay can result from lack of non-essential modifications. Molecular Cell 21(1): 87-96. PMID: 16387656. [preview in: Engelke D.R., Hopper A.K. (2006) Modified view of tRNA: stability amid sequence diversity. Molecular Cell 21(2), 144-5. PMID: 16427003.]
Ma X., Yang C., Alexandrov, A., Grayhack E.J., Behm-Ansmant I., Yu Y.T. (2005) Pseudouridylation of yeast U2 snRNA is catalyzed by either an RNA-guided or RNA-independent mechanism. EMBO J. 24(13): 2403-13. PMC1173158.
Cartlidge R.A., Knebel A., Peggie M., Alexandrov, A., Phizicky E.M., Cohen P. (2005) The tRNA methylase METTL1 is phosphorylated and inactivated by PKB and RSK in vitro and in cells. EMBO J. 24(9): 1696–1705. PMC1142581.
Alexandrov, A., Grayhack, E. J., Phizicky, E. M. (2005) tRNA m7G methyltransferase Trm8p/Trm82p: evidence linking activity to a growth phenotype and implicating Trm82p in maintaining levels of active Trm8p. RNA 11:821-830. PMC1370766.
Alexandrov, A., Vignali M., LaCount D.J., Quartley E., de Vries C., De Rosa D., Babulski J., Mitchell S.F., Schoenfeld L.W., Fields S., Hol W.G., Dumont M.E., Phizicky E.M., Grayhack E.J. (2004) A facile method for high-throughput co-expression of protein pairs. Mol. Cell. Proteomics 3: 934-938. PMID:15240823.
Eliseev R., Alexandrov, A., Gunter T. (2004) High-yield expression and purification of p18 form of Bax as an MBP-fusion protein. Protein Expr Purif. 35(2):206-9. PMID: 15135394.
Gunter T.E., Miller L.M., Gavin C.E., Eliseev R., Salter J., Buntinas L., Alexandrov, A., Hammond S., Gunter K.K. (2004) Determination of the oxidation states of manganese in brain, liver, and heart mitochondria. J. Neurochem. 88(2):266-80. PMID: 14690515.
Dutta K., Engler F.A., Cotton L., Alexandrov, A., Bedi G.S., Colquhoun J., Pascal S.M. (2003) Stabilization of a pH-sensitive apoptosis-linked coiled coil through single point mutations. Protein Sci. 12(2):257-65. PMID: 12538889.
Alexandrov, A., Martzen MR., and Phizicky E.M. (2002) Two proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA. RNA 8:1253-1266. PMC1370335.
Dutta K., Cox C.J., Alexandrov, A., Huang H., Basavappa R., Pascal S.M. (2002) Sequence-specific chemical shift assignment and chemical shift indexing of murine apo-Mts1. J. Biomol NMR. 22(2):181-2. PMID: 11883779.
Dutta K., Alexandrov, A., Huang H., Pascal SM. (2001) pH-induced folding of an apoptotic coiled coil. Protein Sci. 10(12):2531-40. PMID: 11714921.
Huang H., Alexandrov, A., Chen X., Barnes T.W. 3rd, Zhang H., Dutta K., Pascal S.M. (2001) Structure of an RNA hairpin from HRV-14. Biochemistry. 40(27):8055-64. PMID: 11434774.
Alexandrov, A., Dutta K., Pascal S.M. (2001) MBP fusion protein with a viral protease cleavage site: one-step cleavage/purification of insoluble proteins. Biotechniques, 30(6):1194-1198. PMID: 11414203.
Our Addgene plasmid collection: www.addgene.org/Andrei_Alexandrov/
Research Opportunities:
- Our graduate PhD Research Assistant (RA) positions are currently filled. When available, openings will be posted here.
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Contact: Andrei Alexandrov, PhD Assistant Professor of Genetics and Biochemistry Clemson University's Institute for Human Genetics Self Regional Hall, Rm 134 114 Gregor Mendel Circle Greenwood, SC 29646 (203)-848-9835 [email protected] www.alexandrovlab.com/ |
Genetics & Biochemistry at Clemson: https://www.clemson.edu/science/academics/departments/genbio/about/profiles/andreia
Clemson University's Institute for Human Genetics (Greenwood, SC): scienceweb.clemson.edu/chg/people/
Clemson University's Institute for Human Genetics (IHG) on Twitter: twitter.com/clemsonchg
Clemson University's Institute for Human Genetics (Greenwood, SC): scienceweb.clemson.edu/chg/people/
Clemson University's Institute for Human Genetics (IHG) on Twitter: twitter.com/clemsonchg
