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Paul M Lizardi PhD

Research Interests

Cancer Genetics/Epigenetics; Cancer biology; Dynamics of abnormal chromatin states in neoplasia and metastasis; DNA amplification technology (MDA, RCA); DNA microarray technology for epigenetic analysis, array-CGH; Proteomics analysis of cancer tissues


Research Summary

The laboratory’s focus is the study of cancer biology, using genomics and proteomics approaches that enable the comprehensive analysis of molecular alterations that occur during cancer development. An important goal of the laboratory is to develop next-generation analytical approaches that can be translated rapidly to clinical research, and ultimately, patient care. The laboratory works closely with a multidisciplinary team that includes research physicians, chemists, as well as applied physics faculty. Current studies include: (a) Whole genome analysis of gains and loses of alleles in head and neck cancer, using comparative genomic hybridization on microarrays; (b) Development of microarray methods for the analysis of chromatin epigenetic states at the level of the whole human genome; (c) Development of fluorescent probes (molecular beacons) for real-time detection of cancer biomarkers in living tissue; (d) Studies on biomarker discovery using advanced protein separation and MALDI-MS/MS proteomics analysis; (e) Integration of genomics and proteomics data obtained from human tissue or animal models to define cancer staging and assess cancer risk.

Extensive Research Description

Current thinking in the cancer field emphasizes the importance of heterogeneity in tumor tissue. Tumors arise through the emergence of clonal cell sub-populations that have selective advantage in a disturbed or damaged tissue environment. The underlying genomic instability of tumors can lead to the continuous re-emergence of new cell sub-populations harboring different genetic or epigenetic alterations. There is evidence that among the cell sub-populations present in tumors, a key component is a group of cells with stem cell properties, and a greater metastatic potential. With the availability of microarray tools for detecting mutations, aneuploidy, DNA methylation changes, as well as RNA expression profiles, one could in principle identify sorted tumor cell sub-populations, including cancer stem cells, by their detailed genetic, epigenetic, and expression signatures. Thus, comprehensive molecular descriptors are likely to become increasingly important in defining the ontogeny and diversity of tumors, and the mechanisms responsible for metastasis and the emergence of drug resistance. Comprehensive molecular analysis also offers opportunities for radically different therapeutic strategies.

The laboratory’s focus is the study of cancer biology, with an emphasis on the role of epigenetic abnormalities. We use experimental approaches that enable the comprehensive analysis of molecular alterations that occur during cancer development. An important goal of the laboratory is to develop next-generation diagnostic, prognostic, and therapeutic tools that can be translated rapidly to clinical research, and ultimately, patient care. The laboratory works closely with a multidisciplinary team that includes research physicians, chemists, bioinformaticists, as well as applied physics faculty. Current studies include: (a) Whole genome analysis of gains and loses of alleles in head an neck cancer, using comparative genomic hybridization on microarrays; (b) Analysis of chromatin epigenetic states at the level of the whole human genome, using microarrays; (c) Development of fluorescent probes for real-time detection of epigenetic biomarkers in living tissue; (d) Studies on biomarker discovery using advanced protein separation and MALDI-MS/MS proteomics analysis; (e) Development of novel cancer therapeutic strategies based on our integrated knowledge of cell epigenetic states.

Technology development in the Lizardi laboratory has led to over 30 issued US patents, including Molecular Beacon technology, Rolling Circle Amplification (RCAT), Isothermal Whole Genome Amplification (MDA-REPLI-g, MDA-GenomiPhi, licensed to Qiagen, AP Biotech), and GenCompass universal microarray technology (licensed to Agilix Corp).


Selected Publications

  • Bindra RS, Schaffer PJ, Meng A, Woo J, Maseide K, Roth ME, Lizardi P, Hedley DW, Bristow RG, Glazer PM. (2004) Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol Cell Biol. 24:8504-18.
  • Roth, M.E. Feng, L. McConnell, K.J., Schaffer, P.J., et al., and Lizardi, P.M. (2004) Expression profiling using a hexamer-based universal microarray. Nature Biotechnology, 22:418-426.
  • Zhou H, Bouwman K, Schotanus M, Verweij C, Marrero JA, Dillon D, Costa J, Lizardi P, Haab BB. (2004) Two-color, rolling-circle amplification on antibody microarrays for sensitive, multiplexed serum-protein measurements. Genome Biol. 5:R28.
  • Lage, J. M., Leamon, J.H., Pejovic, T., Hamann, S., Lacey, M., Dillon, D., Segraves, R., Vossbrinck, B., Gonzalez, A., Pinkel, D., Albertson, D.G., Costa, J. and Lizardi, P.M. (2003) Whole genome analysis of genetic alerations in small DNA samples using hyperbranched strand displacement amplification and array-CGH. Genome Research 13:294.307.
  • Magwene, P. M., Lizardi, P., and Kim, J. (2003) Reconstructing the temporal ordering of biological samples using microarray data. Bioinformatics. 19:842-50.
  • Ladner, D.P., Leamon, J.H., Hamann, S., Tarafa, G., Strugnell, T., Dillon, D., Lizardi, P.M., and Costa, J. Multiplex detection of hotspot mutations by rolling circle enabled universal microarrays. Laboratory Invest. (2001) 81:1079-1086.
  • Zhong, X., Lizardi, P.M., Huang, X., Bray-Ward, P., and Ward, D.C. (2001) Visualization of Oligonucleotide Probes and Point Mutations in Interphase Nuclei and DNA Fibers Using Rolling Circle DNA Amplification. Proc. Natl. Acad. Sci. USA 98:3940-3945.
  • Lizardi, P.M., Huang, X., Zhu, Z., Bray-Ward, P., Thomas, D.C., and Ward, D.C (1998) Mutation detection and single molecule counting using isothermal rolling circle amplification. Nature Genetics 19:225-232
  • Lage, J.M., et al. (2003). Whole genome analysis of genetic alerations in small DNA samples using hyperbranched strand displacement amplification and array-CGH. Genome Res. 13:294-307.
  • Magwene, P.M., Lizardi, P., and Kim, J. (2003). Reconstructing the temporal ordering of biological samples using microarray data. Bioinformatics 19:842-50.

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