Faculty

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Ite A. Laird, PhD
Associate Professor of Surgery
Associate Dean For Graduate Affairs (Ph.D. Programs)
Director of Pibbs
Surgery
NOR 6420 Health Sciences Campus Los Angeles
+1 323 865 0655

Overview

Dr. Laird-Offringa is Associate Professor of Surgery and of Biochemistry & Molecular Medicine at USC Keck School of Medicine. She received her Ph.D. in 1991 from University of Leiden (Netherlands), and she undertook a postdoctoral research fellowship from 1991–1996 at Harvard Medical School (Boston, MA). She joined the USC faculty in 1966. Research in the Laird-Offringa laboratory is/has been funded by the National Institutes of Health, American Lung Association, the Wright Foundation, the Whittier Translational Research Fund, the Mesothelioma Applied Research Foundation, Joan's Legacy, the Department of Defense, the Tobacco Related Disease Research Fund, the Thomas G Labrecque Foundation, the V Foundation, the Canary Foundation, the Kazan Foundation, the Hoag Family Foundation, the California Community Foundation, and private donations from many generous individuals, including the Mettler family, Wally and Conya Pembroke, Michelle and Paul Zygielbaum, Steven Schwatrz, Sharon Binder, Bonnie and Tony Addario, Larry Auerbach and Judy Glick.

The Laird-Offringa lab studies the cancer that kills the most Americans every year (over 150,000 people, or a full Boeing 747 of people per day). More people die of lung cancer than from breast, prostate, and colon cancer combined. The high death rate is largely a result of the absence of accurate early detection tools.

To develop markers for molecular diagnosis of lung cancer, we are studying DNA methylation patterns in lung cancer. This work is carried out in collaboration with a multidisciplinary team of investigators inside and outside USC. We have concentrated most on lung adenocarcinoma, the most commonly diagnosed type of lung cancer, arising in the lung periphery.

One aspect of early detection is risk classification; the subjects at highest risk should be screened. The Laird-Offringa lab is therefore studying the role of single nucleotide polymorphisms in lung cancer predisposition.

We are also interested in the molecular process underlying cancerous transformation. To better understand how lung epithelium can become abnormal during cancer development, it is key to understand how normal lung epithelium differentiates and responds to injury. Thus, in collaboration with the laboratory of Dr. Zea Borok and Dr. Beiyun Zhou, we study the epigenetic basis for normal alveolar epithelial cell differentiation.

The Laird-Offringa lab also studies small cell lung cancer (SCLC), the most aggressive type of lung cancer. SCLC rapidly metastasizes and patients have an average 5-year survival of just 6%. We are analyzing patients' anti-cancer immune responses to see how these could be leveraged for therapy.

Lastly, we are interested in protein engineering and biomolecular interactions, which are key to the development of new drugs and therapies.

Publications

Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations. Hum Mol Genet. 2016 Dec 26. View in: PubMed

Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study. PLoS Med. 2016 Dec; 13(12):e1002162. View in: PubMed

Pleiotropic Analysis of Lung Cancer and Blood Triglycerides. J Natl Cancer Inst. 2016 Dec; 108(12). View in: PubMed

Data on isoaspartylation of neuronal ELAVL proteins. Data Brief. 2016 Dec; 9:1052-1055. View in: PubMed

Cross-species Transcriptome Profiling Identifies New Alveolar Epithelial Type I Cell-specific Genes. Am J Respir Cell Mol Biol. 2016 Oct 17. View in: PubMed

Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4. J Neuroimmunol. 2016 Oct 15; 299:70-78. View in: PubMed

An Evolved RNA Recognition Motif That Suppresses HIV-1 Tat/TAR-Dependent Transcription. ACS Chem Biol. 2016 Aug 19; 11(8):2206-15. View in: PubMed

The importance of detailed epigenomic profiling of different cell types within organs. Epigenomics. 2016 Jun; 8(6):817-29. View in: PubMed

GRP78 Regulates ER Homeostasis and Distal Epithelial Cell Survival During Lung Development. Am J Respir Cell Mol Biol. 2016 Jan 27. View in: PubMed

Combinations of differentiation markers distinguish subpopulations of alveolar epithelial cells in adult lung. Am J Physiol Lung Cell Mol Physiol. 2016 Jan 15; 310(2):L114-20. View in: PubMed

Molecular portraits of epithelial, mesenchymal, and hybrid States in lung adenocarcinoma and their relevance to survival. Cancer Res. 2015 May 01; 75(9):1789-800. View in: PubMed

Transcriptomic Profiling of Primary Alveolar Epithelial Cell Differentiation in Human and Rat. Genom Data. 2014 Dec 1; 2:105-109. View in: PubMed

EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk. Oncogene. 2014 Sep 04; 33(36):4464-73. View in: PubMed

Knockout mice reveal key roles for claudin 18 in alveolar barrier properties and fluid homeostasis. Am J Respir Cell Mol Biol. 2014 Aug; 51(2):210-22. View in: PubMed

Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue. Nat Commun. 2014; 5:3365. View in: PubMed

CDKN2A/p16 inactivation mechanisms and their relationship to smoke exposure and molecular features in non-small-cell lung cancer. J Thorac Oncol. 2013 Nov; 8(11):1378-88. View in: PubMed

The role of the C-terminal helix of U1A protein in the interaction with U1hpII RNA. Nucleic Acids Res. 2013 Aug; 41(14):7092-100. View in: PubMed

Analysis of protein-RNA complexes involving a RNA recognition motif engineered to bind hairpins with seven- and eight-nucleotide loops. Biochemistry. 2013 Jul 16; 52(28):4745-7. View in: PubMed

Integrated transcriptomic and epigenomic analysis of primary human lung epithelial cell differentiation. PLoS Genet. 2013 Jun; 9(6):e1003513. View in: PubMed

Epigenetic therapy in lung cancer. Front Oncol. 2013; 3:135. View in: PubMed

DNA binding by GATA transcription factor suggests mechanisms of DNA looping and long-range gene regulation. Cell Rep. 2012 Nov 29; 2(5):1197-206. View in: PubMed

Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression. Genome Res. 2012 Jul; 22(7):1197-211. View in: PubMed

DNA methylation changes in atypical adenomatous hyperplasia, adenocarcinoma in situ, and lung adenocarcinoma. PLoS One. 2011; 6(6):e21443. View in: PubMed

Genome-scale screen for DNA methylation-based detection markers for ovarian cancer. PLoS One. 2011; 6(12):e28141. View in: PubMed

Small-cell lung cancer-associated autoantibodies: potential applications to cancer diagnosis, early detection, and therapy. Mol Cancer. 2011; 10:33. View in: PubMed

HuR/methyl-HuR and AUF1 regulate the MAT expressed during liver proliferation, differentiation, and carcinogenesis. Gastroenterology. 2010 May; 138(5):1943-53. View in: PubMed

Immune response in lung cancer mouse model mimics human anti-Hu reactivity. J Neuroimmunol. 2009 Dec 10; 217(1-2):38-45. View in: PubMed

A global benchmark study using affinity-based biosensors. Anal Biochem. 2009 Mar 15; 386(2):194-216. View in: PubMed

Low level anti-Hu reactivity: A risk marker for small cell lung cancer? Cancer Detect Prev. Low level anti-Hu reactivity: A risk marker for small cell lung cancer? Cancer Detect Prev. 2009; 32(4):292-9. View in: PubMed

Conformationally restricted nucleotides as a probe of structure-function relationships in RNA. RNA. 2008 Aug; 14(8):1632-43. View in: PubMed

DNA methylation-based biomarkers for early detection of non-small cell lung cancer: an update. Mol Cancer. 2008; 7:81. View in: PubMed

Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer. Mol Cancer. 2008; 7:62. View in: PubMed

DNA methylation profile of 28 potential marker loci in malignant mesothelioma. Lung Cancer. 2007 Nov; 58(2):220-30. View in: PubMed

Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma. Mol Cancer. 2007; 6:70. View in: PubMed

The role of DNA methylation in the development and progression of lung adenocarcinoma. Dis Markers. 2007; 23(1-2):5-30. View in: PubMed

The role of RNA structure in the interaction of U1A protein with U1 hairpin II RNA. RNA. 2006 Jul; 12(7):1168-78. View in: PubMed

Kinetic analysis of a high-affinity antibody/antigen interaction performed by multiple Biacore users. Anal Biochem. 2006 May 15; 352(2):208-21. View in: PubMed

The role of positively charged amino acids and electrostatic interactions in the complex of U1A protein and U1 hairpin II RNA. Nucleic Acids Res. 2006; 34(1):275-85. View in: PubMed

Distinct DNA methylation profiles in malignant mesothelioma, lung adenocarcinoma, and non-tumor lung. Lung Cancer. 2005 Feb; 47(2):193-204. View in: PubMed

Kinetic analysis of the role of the tyrosine 13, phenylalanine 56 and glutamine 54 network in the U1A/U1 hairpin II interaction. Nucleic Acids Res. 2005; 33(9):2917-28. View in: PubMed

A comparison of cluster analysis methods using DNA methylation data. Bioinformatics. 2004 Aug 12; 20(12):1896-904. View in: PubMed

Solution structure of the complex formed by the two N-terminal RNA-binding domains of nucleolin and a pre-rRNA target. J Mol Biol. 2004 Apr 2; 337(4):799-816. View in: PubMed

Classification of individual lung cancer cell lines based on DNA methylation markers: use of linear discriminant analysis and artificial neural networks. J Mol Diagn. 2004 Feb; 6(1):28-36. View in: PubMed

Characterization of the interaction between neuronal RNA-binding protein HuD and AU-rich RNA. J Biol Chem. 2003 Oct 10; 278(41):39801-8. View in: PubMed

Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by CARM1. Coactivator-associated arginine methyltransferase. J Biol Chem. 2002 Nov 22; 277(47):44623-30. View in: PubMed

Complex role of the beta 2-beta 3 loop in the interaction of U1A with U1 hairpin II RNA. J Biol Chem. 2002 Sep 6; 277(36):33267-74. View in: PubMed

DNA methylation analysis: a powerful new tool for lung cancer diagnosis. Oncogene. 2002 Aug 12; 21(35):5450-61. View in: PubMed

Hierarchical clustering of lung cancer cell lines using DNA methylation markers. Cancer Epidemiol Biomarkers Prev. 2002 Mar; 11(3):291-7. View in: PubMed

Kinetic studies of RNA-protein interactions using surface plasmon resonance. Methods. 2002 Feb; 26(2):95-104. View in: PubMed

Two functionally distinct steps mediate high affinity binding of U1A protein to U1 hairpin II RNA. J Biol Chem. 2001 Jun 15; 276(24):21476-81. View in: PubMed

Post-transcriptional deregulation of myc genes in lung cancer cell lines. Am J Respir Cell Mol Biol. 2000 Oct; 23(4):560-5. View in: PubMed

HuD RNA recognition motifs play distinct roles in the formation of a stable complex with AU-rich RNA. Mol Cell Biol. 2000 Jul; 20(13):4765-72. View in: PubMed

In vitro genetic analysis of RNA-binding proteins using phage display. Methods Mol Biol. 1999; 118:189-216. View in: PubMed

RNA-binding proteins tamed. Nat Struct Biol. 1998 Aug; 5(8):665-8. View in: PubMed

In vitro genetic analysis of RNA-binding proteins using phage display libraries. Methods Enzymol. 1996; 267:149-68. View in: PubMed

Analysis of RNA-binding proteins by in vitro genetic selection: identification of an amino acid residue important for locking U1A onto its RNA target. Proc Natl Acad Sci U S A. 1995 Dec 5; 92(25):11859-63. View in: PubMed

What determines the instability of c-myc proto-oncogene mRNA? Bioessays. What determines the instability of c-myc proto-oncogene mRNA? Bioessays. 1992 Feb; 14(2):119-24. View in: PubMed

Rapid c-myc mRNA degradation does not require (A + U)-rich sequences or complete translation of the mRNA. Nucleic Acids Res. 1991 May 11; 19(9):2387-94. View in: PubMed

Poly(A) tail shortening is the translation-dependent step in c-myc mRNA degradation. Mol Cell Biol. 1990 Dec; 10(12):6132-40. View in: PubMed

Analysis of polyadenylation site usage of the c-myc oncogene. Nucleic Acids Res. 1989 Aug 25; 17(16):6499-514. View in: PubMed

Complementation of Agrobacterium tumefaciens tumor-inducing aux mutants by genes from the T(R)-region of the Ri plasmid of Agrobacterium rhizogenes. Proc Natl Acad Sci U S A. 1986 Sep; 83(18):6935-9. View in: PubMed

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