Assistant Professor of Oncology
Department of Cancer Genetics
Roswell Park Cancer Institute
Elm and Carlton Streets
Buffalo, NY 14263
Telephone: (716) 845-1556
Fax: (716) 845-1698
E-mail: Ping.Liang@RoswellPark.org

Current Program

• Development of a bioinformatics resource at RPCI
• Computational analysis of cancer cytogenetic data
• Identification and database compilation of polymorphic retrotransposon insertions in humans
• Development of bioinformatics tools for analyzing gene expression and array CGH data and for gene annotation
• The mechanism of genomic rearrangements and their contributions to cancer predisposition
• Discovery of cancer-related new genes, new gene functions, and new pathways via bioinformatics approaches in collaboration with other scientists at RPCI and UB.
  

Laboratory Personnel

Sami Azrak PhD - Student
Lei Song MS - Research Affiliate
Jianmin Wang PhD

Description of Research

Bioinformatics resource at RPCI: The arrival of genomic era has been changing the ways and strategies of biomedical research providing us with both ample opportunities and challenges. For examples, with the availability of whole genome sequences, it?s possible to discover new genes, and new pathways, and to clone gene without involving wet experiments. It?s also possible to examine the expression of all genes in a genome related to a specific biological event simultaneously using Gene Chip/MicroArray technology. A key to success in this genomic and post-genomic era is to have the capability to fetch and manipulate the vast amount of biological data available from both public and private/commercial sources and be able to extract meaningful information in a timely fashion. A bioinformatics resource center hosting all the necessary biological databases and software is being established to allow fast access and or automatic large scale analysis of genome data. In addition to the standard bioinformatics services, we are also dedicated to the development of innovative and unique bioinformatics software for facilitating gene discoveries related to human cancer. Detailed information about this resource is available at http://falcon.roswellpark.org.

Computational analysis of cancer cytogenetics data: Characterization of non-random recurrent chromosomal aberrations has proven to be a useful instrument for identification of genes related to human cancers and for improving diagnosis and prognosis. Cytogenetic data, however, are highly encrypted and chromosomal aberrations show a high degree of complexity, making the systematical analysis of cytogenetic data very challenging. More critical chromosomal breakpoints and complex cytogenetic patterns characteristic of genetic diseases await to be discovered using comprehensive cytogenetic data analyzed with new strategies and methodologies. We have developed a new computer program, KaryoReader (KR), for facilitating systematic analysis of cytogenetic data. KR is a web-based program that decodes karyotypic data and calculates all implied chromosomal aberrations. The current version of KaryoReader handles karyotypic data written using ISCN 1995. KR outputs calculated chromosomal aberrations in a tabulated format which are ready for systematic statistical analysis of large scale cytogenetic data. Current applications of KR include: 1) with KR processed data supplemented to cytogenetics databases, such as the NCI Mitelman database, it allows the retrieval all cases that involve aberrations both directly (as breakpoint) and indirectly (implied, not available traditionally) for any specific chromosome regions; 2) characterization of evolution pathways for chromosomal aberrations through comparison of cytogenetic signatures of specific tumors at different stages of tumorigenesis and/or treatment; 3) identification of novel and complex cytogenetic signatures for specific types of cancer by analyzing large data sets; 4) exploration of any global patterns for all chromosomal aberrations involved in human cancers by analyzing all available cytogenetic data. The KR program is accessible on the web at http://falcon.roswellpark.org/KR/.

Human genetic polymorphisms caused by retrotransposon insertions: Alu and L1 are the two major types of retrotransposable elements in the human genome with ~1 million and half million members, respectively, and together they contribute to about 30% of the genome. Alu and L1 elements are known to play important roles in the genome by participating protein coding via alternative splicing or generating new genes, by generating deletions and duplication of genomic sequences via de novo insertions and homologous recombination, and by altering gene regulation via changing DNA composition of promoters and regulatory regions and suppressing transcription. In addition, Alu elements are also known to be the main target of RNA editing in the human genome. Both Alu and L1 elements are still active in the human genome and their recent insertions generate genetic polymorphics (for their presence and absence) in the human populations, and these types of genetic polymorphisms are partially responsible for many types of human genetic diseases. Because Alu and L1 insertions are unique events that are identical-by-descent and free of homoplasy, they have been useful in genetic mapping and population genetics studies. In my laboratory, we study several aspects of Alu and L1 elements: 1) the development of new methods for efficient identification of polymorphic Alus and L1s; 2) non-classic mechanisms of Alu and L1 insertions; 4) impact of Alu and L1 insertions on gene functions; 4) Compilation of human genetic polymorphisms related to Alu and L1 insertions. Compilation of all known human retrontransposon insertion polymorphisms into a databases (dbRIP, available at http://falcon.roswellpark.org:9090/index.html).

Key Publications

• Glenn ST, Jones CA, Liang P, Kaushik D, Gross KW, Kim HL.  Expression profiling of renal tumors by quantitative PCR using frozen and archival tissue.  Biotechniques, In press.
• Cotton RGH, Beckmann J, Blumenfeld O, Brookes A, Brown AF, Carrera P, Cox D, den Dunnen JT, Gottlieb B, Greenblatt B, Hilbert P, Lehvaslaiho H, Liang P, Marsh S, Nebert D,  Rossetti D, Scriver C, Summar M, Tolan D, Verma I, Vihinen M. Definitions of locus Specific databases and their curation. Hum Mutat (In press)
• Smiraglia D,  Kazhiyur-Mannar R, Oakes C, Wu Y, Liang P, Ansari T, Su J, Rush L, Smith L, Yu L, Liu C, Dai Z, Chen S, Wang S, Costello JF, Ioshikhes I, Dawson D, Hong J, Teitell M, Szafranek A. A Restriction Landmark Genomic Scanning (RLGS) spot identification by second generation virtual RLGS in multiple genomes with multiple enzyme combinations. BMC Genomics, In press.
• Han K, Lee J, Meyer TJ,  Wang J, Sen SK, Srikanta D, Liang P, Batzer MA. Alu recombination-mediated structural deletions in the chimpanzee genome.  PLos Genet 2007;3(10):1939-1949.
• Lo K, Shankar G, Rossi M, Burkhardt T, Liang P, Cowell JK. Overlay tool for aCGHViewer: an analysis module built for aCGHViewer used to combine different microarray platforms for visualization. Cancer Inform 2007; 3:309-319.
• Chattopadhyay S, Tracy E, Liang P, Robledo O, Rose-John S, Baumann H. Interleukin-31 and oncostatin-m mediate distinct signaling reactions and response patterns in lung epithelial cells. J Biol Chem 2007; 282:3014-3026.  
• Wu J, Pan D, Song L, Liang P, Yang L, Li F. Molecular mechanism of upregulation of survivin transcription by the AT-rich DNA-binding antitumor agent, Hoechst33342: evidence for survivin involvement in drug resistance. Nucleic Acids Res 2007; 35:2390-2402.
• Blickwedehl J, McEvoy S, Wong I, Kousis P, Clements J, Elliott R, Cresswell P, Liang P, Bangia N.  Proteasomes and proteasome activator 200 kd (pa200) accumulate on chromatin in response to ionizing radiation.  Radiat Res 2007; 167:663-674.
• Lee J, Cordaux R, Han K, Wang J, Hedges DJ, Liang P, Batzer MA.  Different evolutionary fates of recently integrated human and chimpanzee LINE-1 retrotransposons.  Gene 2007; 390:18-27.
• Konkel MK, Wang J, Liang P, Batzer MA.  Identification and characterization of novel polymorphic LINE-1 insertions through comparison of two human genome sequence assemblies.  Gene 2007; 390:28-38.
• Rossetti S, Hoogevenn AT, Liang P, Stanciu C, van der Spek P, Sacchi N.  A distinct epigenetic signature at targets of a leukemia protein  BMC Genomics 2007; 8:38.
• Kim YJ, Ahn YJY, Liang P, Ip C, Zhang Y, Park YM.  Human prx1 gene is a target of Nrf2 and is up-regulated by hypoxia/reoxygenation.  Cancer Res 2007;67(2)546-554.
• Li L, McVety S, Younan R, Liang P, DuSart D, Gordon P, Hutter P, Hogervorst FB, Chong G, Foulkes WD.  Distinct patterns of Germ-Line Deletions in MLH1 and MSH2 in hereditary non-polyposis colorectal cancer families:  The role of Alu sequences.  Human Mutat 27:388, 2006.
• Ramachandran L, Burhans LT, Laun P, Wang J, Liang P, Weinberger M, Wissing S, Jaolim S, Madeo SB, Breitenbach M, Burhans WC. Evidence for ORC-dependent repression of buddingyeast genes induced by starvation and other stresses.  FEMS Yeast Res 2006; 6:763-776. 
• Li W, He M, Zhou H, Bourne J, Liang P.  Mutation data integration in gene-oriebted files of Hermansky-Pudlak Syndrome database.    Human Mutat 2006; 27:402-407.
• Wang J, Song L, Grover D, Azrak S, Batzer MA, Liang P.  dbRIP:  a highly integrated database of retrotransoson insertion polymorphisms in humans.  Human Mutat 2006; 27:323-329.
• Shankar G, Rossi MR, McQuaid DE, Conroy JM, Gaile DG, Cowell JK, Nowak NJ, Liang P.  aCGHViewer:  a generic visualization tool for aCGH data.  Cancer Inform 2006; 2:36-43.
• Wang J, Song L, Gonder MK, Azrak S, Ray D, Batzer MA, Tishkoff SA, Liang P. Whole genome computational comparative genomics: a fruitful approach for ascertaining Alu insertion polymorphisms. Gene 2006; 365:11-20.
• Laun P, Ramachandran L, Jarolim S, Herker E, Liang P, Wang J, Weinberger W, Burhans DT, Suter B, Madeo F, Burhans WC, Breitenbach M. A. Comparison of the aging and apoptotic transcriptome of Saccharomyces cerevisiae. FEMS Yeast Res 2006; 5:1261-1272.
• Liang P, Nair JR, Song L, McGuire JJ, Dolnick BJ. Comparative genomic analysis reveals a novel mitochondrial isoform of human rTS protein and unusual phylogenetic distribution of the rTS gene. BMC Genomics 2005; 6:125:1-10.
• Charbonnier F, Baert-Desurmont S, Liang P, Di Fiore F, Martin C, Frerot S, Olschwang S, Wang Q, Buisine M-P, Gilbert B, Nilbert M, Lindblom A, Frebourg T. The 5' region of the MSH2 gene involved in hereditary non-polyposis colorectal cancer contains a high density of recombinogenic sequences. Hum Mutat 2005; 26:255-261.
• *Han K, *Sen SK, *Wang J, Callinan PA, Lee J, Cordaux R, Liang P, Batzer MA. Genomic rearrangements by LINE-1 insertion-mediated deletion in the human and chimpanzee lineages. Nucleic Acids Res 2005; 33:13:4040-4052. * Co-first authors.
• Callinan PA, Wang J, Herke SW, Garber RK, Liang P, Batzer MA. Alu retrotransposition-mediated deletion. J Mol Biol 2005; 348(4)791-800.
• Wu J, Ling X, Pan D, Apontes P, Song L, Liang P, Altieri DC, Beerman T, Li F. Molecular mechanism of inhibition of survivin transcription by the GC-rich sequence-selective DNA binding antitumor agent, hedamycin: evidence of survivin down-regulation associated with drug sensitivity. J Biol Chem 2005; 280:(10):9745-9751.
• Chen H, Wang J, Liang P, Karsay-Klein M, James AA, Brazeau D, Yan G. Microarray analysis for identification of Plasmodium-refractoriness candidate genes in mosquitoes. Genome 2004; 6:1061-1070.
• Still IH, Vettaikkorumakankauv AK, DiMatteo A, Liang P. Structure-function evolution of the transforming acidic coiled coil genes revealed by analysis of phylogenetically diverse organisms. BMC Evol Biol 2004; 4(1):16.
• Liang P, Jones CA, Bisgrove BW, Song L, Glenn ST, Yost HJ, Gross KW. Genomic characterization and expression analysis of the first non-mammalian renin genes from zebrafish and pufferfish. Physiol Genomics 2004; 16:314-322.
• Ghadersohi A, Odunsi K, Winston JS, Lele S, Collins Y, Greco WR, Liang P, Sood AK. Prostate derived Ets transcription factor shows better tumor-association than other cancer-associated molecules. Oncol Rep 2004; 11:453-458.
• Oulton MM, Amons R, Liang P, MacRae TH. A 49kDA microtubule cross-linking protein from Artemia franciscana is a coenzyme A-transferase. Eur J Biochem 2003; 270:4962-4972.
• Chen Y, Vujcic S, Liang P, Diegelman P, Kramer DL, Porter CL. Genomic identification and biochemical characterization of a second spermidine/spermine n1-acetyltransferase. Biochem J 2003; 373:661-667.
• Wang J, Liang P. Digi-Northern digital expression analysis of query genes based on ESTs. Bioinformatics. Bioinformatics 2003; 19:653-654.
• Vujcic S, Liang P, Diegelman P, Kramer DL, Porter CL. Genomic identification and biochemical characterization of the mammalian polyamine oxidase involved in polyamine back-convertion. Biochem J 2003; 370:19-28.
• Zhang Q, Zhao B, Li W, Oiso N, Novak EK, Rusiniak ME, Gautam R, Chintala S, O'Brien EP, Zhang Y, Roe BA, Elliott RW, Eicher EM, Liang P, Kratz C, Legius E, Spritz RA, O'Sullivan TN, Copeland NG, Jenkins NA, Swank RT. Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndromes type 5 and 6. Nat Genet 2003; 33:145-153.  

Additional PubMed Output is Available at the following site.