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 Center for Human Genetics. We use forward genetics to identify and study disease-associated human pathways of RNA biogenesis, regulation, and surveillance.
To conduct forward genetic interrogation of RNA pathways, we use ultra high-throughput methods that employ CRISPR-based mutagenesis of the human genome and FACS (fluorescence-activated cell sorting). 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 currently focusing on those regulating levels of the human nuclear long non-coding RNA MALAT1. |
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Publications:
Che R., Mirani B., Panah M., Chen X., Luo H., and Alexandrov A. (2025) Identification of Two Elusive Human Ribonuclease MRP-Specific Protein Components. https://www.biorxiv.org/content/10.1101/2025.01.19.633795v1 (in review at Cell Reports).
Inventors: Alexandrov, A., Che, R., Mirani, B., Panah, M. (2024) Bacteria-Free Approach for Expressing Nucleic Acids and Proteins in Eukaryotic Cells. CURF Ref. 2024-008. U.S. Patent Application No. 18/949,053.
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. (2024) Identification of Human Pathways Acting on Nuclear Non-Coding RNAs Using the Mirror Forward Genetic Approach.
https://biorxiv.org/cgi/content/short/2024.09.26.615073v2 (in review at Nature Communications).
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.
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. 2013; 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.
Inventors: Alexandrov, A., Che, R., Mirani, B., Panah, M. (2024) Bacteria-Free Approach for Expressing Nucleic Acids and Proteins in Eukaryotic Cells. CURF Ref. 2024-008. U.S. Patent Application No. 18/949,053.
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. (2024) Identification of Human Pathways Acting on Nuclear Non-Coding RNAs Using the Mirror Forward Genetic Approach.
https://biorxiv.org/cgi/content/short/2024.09.26.615073v2 (in review at Nature Communications).
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.
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. 2013; 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.
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 Center 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 University: www.clemson.edu/science/departments/genetics-biochemistry/people/profiles/andreia
Clemson Center for Human Genetics (Greenwood, SC): scienceweb.clemson.edu/chg/people/
Clemson Center for Human Genetics (CHG) on Twitter: twitter.com/clemsonchg
Clemson Center for Human Genetics (Greenwood, SC): scienceweb.clemson.edu/chg/people/
Clemson Center for Human Genetics (CHG) on Twitter: twitter.com/clemsonchg
