Overview

Dr. 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 (the Netherlands), and she undertook a postdoctoral research fellowship from 1991–1996 at Harvard Medical School (Boston, MA). She joined the USC faculty in 1996. Research in the 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, STOP Cancer, and private donations from many generous individuals, including the Mettler family, Wally and Conya Pembroke, Michelle and Paul Zygielbaum, Steven Schwartz, Sharon Binder, Bonnie and Tony Addario, Larry Auerbach, Judy Glick, and others.

The Offringa lab studies the cancer that kills the most Americans every year (over 125,000 people per year, almost one 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 the result of detecting this cancer too late.

On the one hand, the Offringa lab focuses on lung adenocarcinoma (LUAD), the most common histological type of lung cancer. It arises in the alveoli or air sacs, which make up 90% of the lung surface and, for one adult, constitute a surface the size of half a tennis court. The alveolar epithelium is thus inordinately exposed to airborne environmental carcinogens and viruses. We study global gene expression in primary LUAD samples and cell lines, the epigenetic basis of normal alveolar lung development, the effects of the environment on the lung epigenome, the interplay between the genome and the epigenome, and single cell transcriptomics.
We are also studying the role of single nucleotide polymorphisms in lung cancer predisposition; one aspect of early detection is risk classification. Understanding how genetic differences between individuals influences cancer risk will help identify the subjects at highest risk, for whom it is even more important that they should be screened.

Another area of focus of the Offringa lab is 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 8%. We are analyzing patients’ anti-cancer immune responses to see how these could be leveraged for targeted immunotherapy.

Lastly, we are interested in protein engineering and biomolecular interactions, which are key to the development of new drugs and therapies. The Offringa lab oversees the Norris Comprehensive Cancer Center’s SwitchSENSE DRX2 Biosensor, which is used to analyze biomolecular interactions.

Publications

  • Mentoring Minority Cancer Researchers of Tomorrow: Comparison of the Face-to-Face, Virtual, and Hybrid Training Methods of the CaRE2 Summer Cancer Research Education and Training Program J Cancer Educ. 2024 Aug; 39(4):405-412. . View in PubMed
  • Design and Realization of Lung Organoid Cultures for COVID-19 Applications Biodes Manuf. 2023 Nov; 6(6):646-660. . View in PubMed
  • Florida-California Cancer Research, Education and Engagement (CaRE2) Health Equity Center: Structure, Innovations, and Initial Outcomes Cancer Control. 2023 Jan-Dec; 30:10732748231197878. . View in PubMed
  • Lack of racial and ethnic diversity in lung cancer cell lines contributes to lung cancer health disparities Front Oncol. 2023; 13:1187585. . View in PubMed
  • Bio-Design and Manufacturing Design and realization of lung organoid cultures for COVID-19 applications. 2023. . View in PubMed
  • Development of human alveolar epithelial cell models to study distal lung biology and disease iScience. 2022 Feb 18; 25(2):103780. . View in PubMed
  • Comprehensive epigenomic profiling of human alveolar epithelial differentiation identifies key epigenetic states and transcription factor co-regulatory networks for maintenance of distal lung identity BMC Genomics. 2021 Dec 18; 22(1):906. . View in PubMed
  • Developing a Novel Framework for an Undergraduate Cancer Research Education and Engagement Program for Underrepresented Minority Students: the Florida-California CaRE2 Research Education Core (REC) Training Program J Cancer Educ. 2021 10; 36(5):914-919. . View in PubMed
  • Endoplasmic reticulum chaperone GRP78/BiP is critical for mutant Kras-driven lung tumorigenesis Oncogene. 2021 05; 40(20):3624-3632. . View in PubMed
  • The Sulfotransferase SULT1C2 Is Epigenetically Activated and Transcriptionally Induced by Tobacco Exposure and Is Associated with Patient Outcome in Lung Adenocarcinoma Int J Environ Res Public Health. 2021 12 31; 19(1). . View in PubMed
  • TENET 20: Identification of key transcriptional regulators and enhancers in lung adenocarcinoma. PLoS Genet. 2020 09; 16(9):e1009023. . View in PubMed
  • Genome-wide integration of microRNA and transcriptomic profiles of differentiating human alveolar epithelial cells Am J Physiol Lung Cell Mol Physiol. 2020 07 01; 319(1):L173-L184. . View in PubMed
  • Integrated Single-Cell RNA-Sequencing Analysis of Aquaporin 5-Expressing Mouse Lung Epithelial Cells Identifies GPRC5A as a Novel Validated Type I Cell Surface Marker Cells. 2020 11 11; 9(11). . View in PubMed
  • Positional integration of lung adenocarcinoma susceptibility loci with primary human alveolar epithelial cell epigenomes Epigenomics. 2018 09; 10(9):1167-1187. . View in PubMed
  • CLDN181 attenuates malignancy and related signaling pathways of lung adenocarcinoma in vivo and in vitro. Int J Cancer. 2018 12 15; 143(12):3169-3180. . View in PubMed
  • Association of internal smoking dose with blood DNA methylation in three racial/ethnic populations Clin Epigenetics. 2018 08 23; 10(1):110. . View in PubMed
  • Cross-Species Transcriptome Profiling Identifies New Alveolar Epithelial Type I Cell-Specific Genes Am J Respir Cell Mol Biol. 2017 03; 56(3):310-321. . View in PubMed
  • 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. 2017 01 15; 26(2):454-465. . View in PubMed
  • Data on isoaspartylation of neuronal ELAVL proteins Data Brief. 2016 Dec; 9:1052-1055. . View in PubMed
  • Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study PLoS Med. 2016 Dec; 13(12):e1002162. . 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
  • Pleiotropic Analysis of Lung Cancer and Blood Triglycerides J Natl Cancer Inst. 2016 12; 108(12). . View in PubMed
  • The 78-kD Glucose-Regulated Protein Regulates Endoplasmic Reticulum Homeostasis and Distal Epithelial Cell Survival during Lung Development Am J Respir Cell Mol Biol. 2016 07; 55(1):135-49. . View in PubMed
  • The importance of detailed epigenomic profiling of different cell types within organs Epigenomics. 2016 06; 8(6):817-29. . View in PubMed
  • An Evolved RNA Recognition Motif That Suppresses HIV-1 Tat/TAR-Dependent Transcription ACS Chem Biol. 2016 08 19; 11(8):2206-15. . View in PubMed
  • Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4 J Neuroimmunol. 2016 10 15; 299:70-78. . 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 01; 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 Feb 27; 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
  • Small-cell lung cancer-associated autoantibodies: potential applications to cancer diagnosis, early detection, and therapy Mol Cancer. 2011 Mar 30; 10:33. . 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
  • 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. 2009; 32(4):292-9.. View in PubMed
  • DNA methylation-based biomarkers for early detection of non-small cell lung cancer: an update Mol Cancer. 2008 Oct 23; 7:81. . 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
  • Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer Mol Cancer. 2008 Jul 10; 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 Oct 29; 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 02; 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 CARM1Coactivator-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 06; 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
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  • 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