Leonard Lipovich, Ph.D.
3228 Scott Hall
540 East Canfield
Detroit, MI 48201
Assistant Professor (also with Neurology); Ph.D., University of Washington, 2003. Genomic complexity; primate comparative genomics; bioinformatics and functional genomics of long noncoding-RNA transcripts; computing the genomic basis of species phenotypic uniqueness.
A formidable conundrum of the post-genomic era is the abundance of eukaryotic transcripts which have limited interspecies conservation, do not encode proteins or small RNAs, and are devoid of known functional roles. My group integrates bioinformatics and experimentation to understand the evolutionary and functional genomics of these long non-protein-coding RNA (lncRNA) transcripts, with an emphasis on their roles in primate, and specifically human, phenotypic uniqueness. We have catalogued primate-specific and noncoding-RNA genes in the human genome. We designed and implemented custom expression microarrays for analysis of the human lncRNA transcriptome. Using these microarrays, we show that numerous primate-specific lncRNAs, as well as non-conserved lncRNAs participating in sense-antisense pairs with known protein-coding genes, are differentially expressed in the human brain, in a variety of systems including development, cocaine abuse, and epilepsy. We are performing RNAi of these lncRNAs in a human neuroblastoma cell line, and already documented cis-regulation of the adjacent known genes by the perturbed lncRNAs, highlighting the limitations of rodent models and the pressing need to use human systems to accurately study RNA-dependent human brain diseases. Our plans include reverse RNAomics by using human neuronally expressed long noncoding RNAs as baits to trap their interacting proteins. We have recently joined multiple international collaborations which focus on regulatory network inference from the primate-specific lncRNA transcriptome, as well as on proteogenomic data integration for empirical verification that lncRNAs are, indeed, not biologically translated in human cells.
Lipovich L, Johnson R, and Lin CY. MacroRNA underdogs in a microRNA world: evolutionary,
regulatory, and biomedical significance of mammalian long non-protein-coding RNA. (invited review article) Biochimica et Biophysica Acta 1799: 597-615, 2010.
Jia H, Osak M, Bogu GK, Stanton LW, Johnson R, and Lipovich L. Genome-wide
computational identification and manual annotation of human long noncoding RNA genes.
RNA 16: 1478-1487, 2010.
Sheik Mohamed J, Gaughwin PM, Lim B, Robson P, and Lipovich L. Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells. RNA 16: 324-337, 2010. Selected for Faculty Of 1000 Biology
Tay SK, Blythe J, and Lipovich L. Global discovery of primate-specific genes in the human
genome. Proc Natl Acad Sci USA 106: 12019-12024, 2009.
Johnson R, Teh CHL, Jia H, Vanisri RR, Pandey T, Lu ZH, Buckley NJ, Stanton LW, and
Lipovich L. Regulation of neural macroRNAs by the transcriptional repressor, REST. RNA 15: 85-96, 2009.
Lee TM and Lipovich L. Structural differences of orthologous genes: insights from human-primate comparisons. Genomics 92: 134-143, 2008. (Article was represented by an issue Cover Illustration, requested by the Editors and provided by the Authors.)
Kunarso G, Wong KY, Stanton LW, and Lipovich L. Detailed characterization of the mouse
embryonic stem cell transcriptome reveals novel genes and intergenic splicing associated with
pluripotency. BMC Genomics 9(1):155 (e-publication), 2008.
Designated as a “Highly Accessed article” by BioMed Central.
Orlov Y, Zhou JT, Lipovich L, Shahab A, and Kuznetsov VA. Quality assessment of the Affymetrix U133A&B probesets by target sequence mapping and expression data analysis. In Silico Biol 7:0041 (e-publication), 2007.
Lin CY, Vega VB, Thomsen JS, Zhang T, Kong SL, Xie M, Chiu KP, Lipovich L, Barnett DH, Stossi F,
Yeo A, George J, Kuznetsov VA, Lee YK, Charn TH, Palanisamy N, Miller LD, Cheung E, Katzenellenbogen BS, Ruan Y, Bourque G, Wei CL, and Liu ET. Whole-genome cartography of estrogen receptor alpha binding sites. PLoS Genetics 3(6):e87 (e-publication), 2007.
Engstrom PG, Suzuki H, Ninomiya N, Akalin A, Sessa L, Lavorgna G, Brozzi A, Luzi L, Tan SL, Yang L, Kunarso G, Ng E, Batalov S, Kai C, Kawai J, Carninci P, Hayashizaki Y, Wells C, Bajic VB, Orlando V, Reid JF, Lenhard B, and Lipovich L. Complex loci in mammalian genomes. PLoS Genetics 2(4):e47 (e-publication), 2006.
Bajic VB, Tan SL, Christoffels A, Schonbach C, Lipovich L, Yang L, Hofmann O, Kruger A, Hide W, Kai C, Kawai J, Hume DA, Carninci P, and Hayashizaki Y. Mice and men: their promoter properties.
PLoS Genetics 2(4):e54 (e-publication), 2006.
Loh YH, Wu Q, Chew JL, Vega VB, Zhang WW, Chen X, Bourque G, George J, Leong B, Liu J, Wong
KY, Sung KW, Lee CW, Zhao XD, Chiu KP, Lipovich L, Kuznetsov VA, Robson P, Stanton LW, Wei CL,
Ruan Y, Lim B, and Ng HH. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nature Genetics 38: 431-440, 2006.
Lipovich L, Vanisri RR, Kong SL, Lin CY, and Liu ET. Primate-specific endogenous cis-antisense
transcription in the human 5q31 protocadherin gene cluster. Journal of Molecular Evolution 62: 73-88, 2006.
Lipovich L and King MC. Abundant novel transcriptional units and unconventional gene pairs on human chromosome 22. Genome Research 16: 45-54, 2006.
Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap CC, Suzuki M, Kawai J, Suzuki H, Carninci P, Hayashizaki Y, Wells C, Frith M, Ravasi T, Pang KC, Hallinan J, Mattick J, Hume DA, Lipovich L, Batalov S, Engstrom PG, Mizuno Y, Faghihi MA, Sandelin A, Chalk AM, Mottagui-Tabar S, Liang Z, Lenhard B, Wahlestedt C; RIKEN Genome Exploration Research Group; Genome Science Group (Genome Network Project Core Group); FANTOM Consortium. Antisense transcription in the mammalian transcriptome. Science 309: 1564-1566, 2005.
Carninci P, FANTOM Consortium member list (including Lipovich L), Hayashizaki Y; RIKEN Genome
Exploration Research Group; Genome Science Group (Genome Network Project Core Group); FANTOM Consortium. The transcriptional landscape of the mammalian genome. Science 309: 1559-1563, 2005.
Lipovich L and King MC. Novel transcriptional units and unconventional gene pairs in the human genome: toward a sequence-level basis for primate-specific phenotypes? Cold Spring Harbor Symposia on Quantitative Biology 68: 461-470, 2003.
Lipovich L, Abkowitz J, King MC, Hughes A, and Quigley JG. Ancient conserved gene clusters,
functional diversification of paralogous genes, and de novo gene generation in duplicons of the human FLVCR locus. Gene 286: 203-213, 2002.
Lipovich L, Lynch ED, Lee MK, and King MC. A novel sodium bicarbonate cotransporter-like gene in an ancient duplicated region: SLC4A9 at 5q31. Genome Biology 2: 0011(e-publication), 2001.