![\"A](\"https:\/\/scienceweb.clemson.edu\/chg\/wp-content\/uploads\/sites\/4\/2023\/04\/andrei-alexandrov-1-g-scaled.jpg\")
<\/a><\/p>\nDr. Andrei Alexandrov<\/p>\n
[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"
Director<\/p>\n","protected":false},"author":4,"featured_media":1326,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"Assistant Professor, Department of Genetics and Biochemistry<\/strong>\r\n\r\nEmail: andreia@clemson.edu\r\n\r\n[button link=\"alexandrovlab.com\" type=\"big\" color=\"silver\" newwindow=\"yes\"] Visit the Alexandrov Lab[\/button]\r\n<\/h3>\r\nBiosketch<\/h3>\r\nBefore joining the Clemson Center for Human Genetics, Dr. Alexandrov was a scientist at Yale University where he studied disease-associated human RNA pathways funded by the National Institute of Neurological Disorder and Stroke and the National Human Genome Research Institute. Dr. Alexandrov received his PhD at the University of Rochester School of Medicine and had his post-doctoral training in the (i) Center for Human Genetics and Molecular Pediatric Disease at the University of Rochester and (ii) Department of Molecular Biochemistry and Biophysics at Yale University. In the lab of Dr. Eric Phizicky in Rochester, Dr. Alexandrov used genetic interaction screening and identified a novel RNA surveillance pathway he named the Rapid tRNA Degradation (RTD) pathway. Subsequently, in the lab of Dr. Joan Steitz at Yale, Dr. Alexandrov developed an ultra-high throughput method that enables forward genetic discovery of genes involved in human RNA surveillance. He applied this approach to identify components of the human nonsense-mediated mRNA degradation (NMD) pathway and is currently using this technology to identify components responsible for biogenesis, regulation, and surveillance of disease-associated human nuclear long non-coding RNAs.\r\n
Research<\/h3>\r\nThe lab of Dr. Alexandrov uses forward genetics and ultra-high throughput CRISPR-based genome interrogation to identify components of disease-associated human RNA pathways. The lab extensively employs fluorescence-activated cell sorting (FACS), complex CRISPR guide RNA libraries, and in vivo<\/em> fluorescence amplification to expand opportunities provided by forward genetics in human cells. The lab\u2019s goal is to identify and tackle components of RNA pathways implicated in devastating human genetic diseases and cancers. Specifically, Dr. Alexandrov lab is interested in:\r\n\r\n\u2013 Forward genetic identification of the pathways of nuclear biogenesis, regulation, and surveillance of human long non-coding RNAs (lncRNAs), exemplified by cancer-associated nuclear lncRNA MALAT1. Dr. Alexandrov\u2019s forward genetic screening identified complexes required for MALAT1 3\u2032 end nuclear surveillance, components required for nuclear MALAT1 mascRNA maturation, and additional candidate genes. Previously, such nuclear lncRNA pathways have been completely refractory to forward genetics.\r\n\r\n\u2013 Discovery of factors in human mRNA surveillance. Our previous work identified multiple known nonsense-mediated mRNA degradation components as well as candidate genes, providing an experimental platform for discovery of additional targets for potential enhancement of nonsense suppression therapies of human genetic disorders.\r\n\r\n\u2013 Development of technology for massive shotgun mutational interrogation of the entire human genome. Unlike traditional knockdowns and knockouts, the approach is intended to interrogate coding, non-coding, and intergenic genomic regions. The method provides an unbiased tool for mutational analysis of the diploid human genome and aims to pinpoint critical residues within multi-functional and essential gene products that could be targeted to inhibit disease-associated human pathways with minimal toxicity.\r\n\r\n\u2013 Genome-scale identification of redundantly acting human gene pairs. Unbiased genome-scale experimental identification of redundantly acting human genes is currently impossible due to prohibitively large number of pairwise gene combinations. The ultra-high throughput screening technology employed by Alexandrov\u2019s lab provides an experimental platform for genome-scale forward genetic discovery of pairwise therapeutic targets within disease-associated human pathways.\r\n
Publications<\/h3>\r\nAlexandrov A.<\/strong>, Shu M.D., Steitz J.A. (2017) Fluorescence Amplification Method for Forward Genetic Discovery of Factors in Human mRNA Degradation. Molecular Cell<\/em>. 65(1):191-201. PMC5301997.\r\n\r\nHerbert K.M., Pimienta G., DeGregorio S.J., Alexandrov A.,<\/strong> Steitz J.A. (2013) Phosphorylation of DGCR8 increases its intracellular stability and induces a progrowth miRNA profile. Cell Reports.<\/strong><\/em> 2013; 5(4):1070-81. PMID: 24239349.\r\n\r\nAlexandrov A.<\/strong>, 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.<\/em> 109(52): 21313-18. PMC3535618.\r\n\r\nAlexandrov A.<\/strong>, 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<\/em>. 25: 1078-90. PMC3093123.\r\n\r\nQuartley E., Alexandrov A.,<\/strong> Mikucki M., Buckner F.S., Hol W.G., DeTitta G.T., Phizicky E.M., Grayhack E.J. (2009) Heterologous expression of L. major<\/em> proteins in S. cerevisiae<\/em>: a test of solubility, purity, and gene recoding. J. Struct. Funct. Genomics.<\/strong><\/em> 10(3):233-47. PMID:19701618.\r\n\r\nAlexandrov A.<\/strong>, 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<\/em> 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<\/em> 21(2), 144-5. PMID: 16427003.]\r\n\r\nMa X., Yang C., Alexandrov A.,<\/strong> 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.<\/em> 24(13): 2403-13. PMC1173158.\r\n\r\nCartlidge R.A., Knebel A., Peggie M., Alexandrov A.<\/strong>,<\/strong> 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.<\/strong><\/em> 24(9): 1696\u20131705. PMC1142581.\r\n\r\nAlexandrov, A.,<\/strong> Grayhack, E. J., Phizicky, E. M. (2005)\u00a0 tRNA m7<\/sup>G methyltransferase Trm8p\/Trm82p: evidence linking activity to a growth phenotype and implicating Trm82p in maintaining levels of active Trm8p. RNA <\/em>11:821-830. PMC1370766.\r\n\r\nAlexandrov A.,<\/strong> 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<\/em>. Cell<\/em>. Prot<\/em>eomics<\/em> 3: 934-938. PMID:15240823.\r\n\r\nEliseev R., Alexandrov A.,<\/strong> Gunter T. (2004) High-yield expression and purification of p18 form of Bax as an MBP-fusion protein. Protein Expr Purif.<\/strong><\/em> 35(2):206-9. PMID: 15135394.\r\n\r\nGunter T.E., Miller L.M., Gavin C.E., Eliseev R., Salter J., Buntinas L., Alexandrov A.,<\/strong> Hammond S., Gunter K.K. (2004) Determination of the oxidation states of manganese in brain, liver, and heart mitochondria. J. <\/strong>Neurochem.<\/strong><\/em> 88(2):266-80. PMID: 14690515.\r\n\r\nDutta K., Engler F.A., Cotton L., Alexandrov A.,<\/strong> Bedi G.S., Colquhoun J., Pascal S.M. (2003) Stabilization of a pH-sensitive apoptosis-linked coiled coil through single point mutations. Protein Sci.<\/strong><\/em> 12(2):257-65. PMID: 12538889.\r\n\r\nAlexandrov A.,<\/strong> Martzen MR., and Phizicky E.M. (2002) Two proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA. RNA<\/em> 8:1253-1266. PMC1370335.\r\n\r\nDutta K., Cox C.J., Alexandrov A.,<\/strong> Huang H., Basavappa R., Pascal S.M. (2002) Sequence-specific chemical shift assignment and chemical shift indexing of murine apo-Mts1. J. Biomol NMR.<\/em> 22(2):181-2. PMID: 11883779.\r\n\r\nDutta K., Alexandrov A.,<\/strong> Huang H., Pascal SM. (2001) pH-induced folding of an apoptotic coiled coil. Protein Sci.<\/em> 10(12):2531-40. PMID: 11714921.\r\n\r\nHuang H., Alexandrov A.,<\/strong> Chen X., Barnes T.W. 3rd, Zhang H., Dutta K., Pascal S.M. (2001) Structure of an RNA hairpin from HRV-14. Biochemistry.<\/strong><\/em> 40(27):8055-64. PMID: 11434774.\r\n\r\nAlexandrov A.,<\/strong> Dutta K., Pascal S.M. (2001) MBP fusion protein with a viral protease cleavage site: one-step cleavage\/purification of insoluble proteins. Biotechniques<\/em>, 30(6):1194-1198. 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