Leonard Lipovich, Ph.D.
Associate Professor with tenure
3228 Scott Hall
540 East Canfield
Detroit, MI 48201
Associate 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.
P, Lipovich L, Grander D, Morris KV.
"Evolutionary conservation of long noncoding RNAs:
sequence, structure, function." Biochim Biophys
Acta. S0304-4165(13)00475-3, PMID:
R, Tarca A, Chaemsaithong P, Miranda J,
Chaiworapongsa T, Jia H, Hassan SS, Kalita CA, Cai
J, Yeo L, Lipovich L. "Transcriptome
interrogation of human myometrium identifies
differentially expressed sense-antisense pairs of
protein-coding and long non-coding RNA genes in
spontaneous labor at term." J Matern Fetal Neonatal
Med. PMID: 24168098, 2013
Wood EJ, Chin-Inmanu K, Jia H, Lipovich L. "Sense-antisense gene pairs: sequence, transcription, and structure are not conserved between human and mouse." Front Genet. 4:183, PMID: 24133500, 2013
Bianchi S, Stimpson CD, Duka T, Larsen MD, Jannsen WG, Collins Z, Bauernfeind AL, Schapiro SJ, Baze WB, McArthur MJ, Hopkins WD, Wildman DE, Lipovich L, Kuzawa CW, Jacobs B, Hof PR, Sherwood CC. "Synaptogenesis and development of pyramidal neuron dendritic morphology in the chimpanzee neocortex resembles humans." Proc Natl Acad Sci USA. 110 Suppl 2: 10395-401, PMID: 23754422, 2013
Kosir MA, Jia H, Ju D, Lipovich L. "Challenging paradigms: long non-coding RNAs in breast ductal carcinoma in situ (DCIS)." Front Genet. 4:50. doi: 10.3389/fgene, PMID: 23577021, 2013
Sterner KN, McGowen MR, Chugani HT, Tarca AL, Sherwood CC, Hof PR, Kuzawa CW, Boddy AM, Raaum RL, Weckle A, Lipovich L, Grossman LI, Uddin M, Goodman M, Wildman DE. "Characterization of human cortical gene expression in relation to glucose utilization." Am J Hum Biol. 25(3): 418-30, PMID: 23559490
Kraus P, Sivakamasundari V, Lim SL, Xing X, Lipovich L, Lufkin T. "Making sense of Dix1 antisense RNA." Dev Biol. 15;376(2): 224-35. PMID: 23415800 2013
Lipovich L, Tarca AL, Cai J, Jia H, Chugani HT, Sterner KN, Grossman LI, Uddin M, Hof PR, Sherwood CC, Kuzawa CW, Goodman M, Wildman DE. "Developmental changes in the transcriptome of human cerebral cortex tissue: Long noncoding RNA transcripts." Cereb Cortex. PMID 23377288, 2013
Miller DJ, Duka T, Stimpson CD, Schapiro SJ, Baze WB, McArthur MJ, Fobbs AJ, Sousa AM, Sestan N, Wildman DE, Lipovich L, Kuzawa CW, Hof PR, and Sherwood CC. "Prolonged myelination in human neocortical evolution." Proc Natl Acad Sci U S A. 109(41):16480-5, 2012
Lipovich L, Dachet F, Cai J, Bagla S, Balan K, Jia H, Loeb JA. "Activity-dependent Human Brain Coding/Non-coding Gene Regulatory Networks." Genetics, e-publication, 2012.
Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan X, Ruan Y, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigó R. "The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression." Genome Res. 22(9):1775-89, 2012
Bánfai B, Jia H, Khatun J, Wood E, Risk B, Gundling WE Jr, Kundaje A, Gunawardena HP, Yu Y, Xie L, Krajewski K, Strahl BD, Chen X, Bickel P, Giddings MC, Brown JB, Lipovich L. "Long noncoding RNAs are rarely translated in two human cell lines." Genome Res. 22(9):1646-57, 2012
Southwood CM, Lipovich L, Gow A. "Tissue-Restricted Transcription from a Conserved Intragenic CpG Island in the Klf1 Gene in Mice." Biol Reprod. e-publication, 2012.
Sterner KN, Weckle A, Chugani HT, Tarca AL, Sherwood CC, Hof PR, Kuzawa CW, Boddy AM, Abbas A, Raaum RL, Grégoire L, Lipovich L, Grossman LI, Uddin M, Goodman M, Wildman DE. "Dynamic gene expression in the human cerebral cortex distinguishes children from adults." PLoS One. 7(5):e37714. e-publication, 2012.
Michelhaugh SK, Lipovich L, Blythe
J, Jia H, Kapatos G, Bannon MJ. "Mining Affymetrix
microarray data for long non-coding RNAs: altered
expression in the nucleus accumbens of heroin
Mittal P, Romero R, Tarca AL, Gonzalez J, Draghici S, Xu Y, Dong Z, Nhan-Chang CL, Chaiworapongsa T, Lye S, Kusanovic JP, Lipovich L, Mazaki-Tovi S, Hassan SS, Mesiano S, Kim CJ. "Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term." J Perinat Med. 38(6):617-43, 2012.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
Goodman M, Sterner KN, Islam M, Uddin M, Sherwood CC, Hof PR, Hou ZC, Lipovich L, Jia H, Grossman LI, Wildman DE. "Phylogenomic analyses reveal convergent patterns of adaptive evolution in elephant and human ancestries." Proc Natl Acad Sci U S A. 106(49):20824-9, 2009.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.
Johnson R, Teh CH, Kunarso G, Wong KY, Srinivasan G, Cooper ML, Volta M, Chan SS, Lipovich L, Pollard SM, Karuturi RK, Wei CL, Buckley NJ, Stanton LW. "REST regulates distinct transcriptional networks in embryonic and neural stem cells." PLoS Biol. 6(10):e256, 2008.
Lim CY, Tam WL, Zhang J, Ang HS, Jia H, Lipovich L, Ng HH, Wei CL, Sung WK, Robson P, Yang H, Lim B. "Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages." Cell Stem Cell. 6;3(5):543-54, 2008.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.
Lim CA, Yao F, Wong JJ, George J, Xu H, Chiu KP, Sung WK, Lipovich L, Vega VB, Chen J, Shahab A, Zhao XD, Hibberd M, Wei CL, Lim B, Ng HH, Ruan Y, Chin KC. "Genome-wide mapping of RELA(p65) binding identifies E2F1 as a transcriptional activator recruited by NF-kappaB upon TLR4 activation." Mol Cell. 17;27(4):622-35, 2007.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.
Ng P, Wei CL, Sung WK, Chiu KP, Lipovich L, Ang CC, Gupta S, Shahab A, Ridwan A, Wong CH, Liu ET, Ruan Y. "Gene identification signature (GIS) analysis for transcriptome characterization and genome annotation." Nat Methods. 2(2):105-11, 2005.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.
Wei CL, Ng P, Chiu KP, Wong CH, Ang CC, Lipovich L, Liu ET, Ruan Y. "5' Long serial analysis of gene expression (LongSAGE) and 3' LongSAGE for transcriptome characterization and genome annotation." Proc Natl Acad Sci U S A. 101(32):11701-6, 2004.
Lipovich L. "Pharmaceutical companies need to broaden research." Drug Discov Today. 1;8(1):18, 2003.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. "Comparative genomics comes of age." Genome Biol. 15;3(8):REPORTS4024, 2002.
Lipovich L, Hughes AL, King MC, Abkowitz JL, Quigley JG. "Genomic structure and evolutionary context of the human feline leukemia virus subgroup C receptor (hFLVCR) gene: evidence for block duplications and de novo gene formation within duplicons of the hFLVCR locus." Gene. 20;286(2):203-13, 2002.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.