University of Nebraska Medical Center
University of Nebraska Medical Center

John LaCava, PhD

Professor, UNMC Department of Biochemistry & Molecular Biology

402-559-4419

John LaCava, PhD

John LaCava, PhD, is a professor in the Department of Biochemistry and Molecular Biology at UNMC. Dr. LaCava received his associate degree in biotechnology from Massachusetts Bay Community College, his bachelor’s degree in biotechnology from the University of California, Davis, and his PhD in molecular genetics from the University of Edinburgh. Following postdoctoral positions in Europe and the United States, Dr. LaCava held faculty appointments at The Rockefeller University and University Medical Center Groningen, before joining UNMC in 2026.

The LaCava laboratory combines innovative approaches drawn from biochemistry, quantitative proteomics, advanced sequencing and computational biology to define the compositions, organization and functions of native macromolecular assemblies. For this, the laboratory draws upon model systems and patient samples, developing enabling technologies while at the same time applying them to fundamental and biomedical questions, allowing previously inaccessible macromolecular assemblies and their roles in human diseases to be elucidated.

A major research focus of the laboratory is the molecular biology of LINE-1 retrotransposons, which are mobile genetic elements that constitute approximately one-fifth of the human genome and become dysregulated in cancers, aging, autoimmune disorders and neurodegenerative diseases. Dr. LaCava’s team has pioneered methods for defining endogenous LINE-1 interaction networks and directly detecting the long-elusive LINE-1 ORF2 protein, providing new insight into how these elements promote genomic instability, viral mimicry, innate immune activation and disease progression.

More broadly, the laboratory investigates macromolecular assemblies formed with endogenous nucleic acids that give rise to viral mimicry — e.g., DNA:RNA hybrids, double-stranded RNAs and Z-form nucleic acids, bound by the receptors and signaling apparatus that recognize these molecules as virus-like danger signals. Through this work, the laboratory seeks to explain how inappropriate activation of innate immune pathways contributes to chronic inflammation, tumor evolution, interferonopathies and age-associated diseases.

By integrating analytical innovation with mechanistic biology, the LaCava laboratory seeks to uncover fundamental principles of cellular organization while laying the foundation for new biomarkers and therapeutic strategies.

  • AS: Biotechnology, Massachusetts Bay Community College, 1998
  • BS: Fermentation/Microbial Biotechnology, University of California, Davis, 2000
  • PhD: Molecular Genetics, University of Edinburgh, 2005

Interactomics, RNA biology, retrotransposons, viral mimicry and innate immunity.

  • Hakhverdyan, Z, M Domanski, L Hough, AA Oroskar, AR Oroskar, S Keegan, DJ Dilworth, KR Molloy, V Sherman, JD Aitchison, D Fenyö, BT Chait, TH Jensen, MP Rout, J LaCava. 2015. Rapid, Optimized Interactomic Screening. Nature Methods. 12:553–560.
  • Taylor, MS, I Altukhov, KR Molloy, P Mita, H Jiang, EM Adney, A Wudzinska, S Badri, D Ischenko, G Eng, KH Burns, D Fenyö, BT Chait, D Alexeev, MP Rout, JD Boeke, J LaCava. 2018. Dissection of affinity captured LINE-1 macromolecular complexes. eLife. 7:e30094
  • Dou, Y, S Kalmykova, M Pashkova, M Oghbaie, H Jiang, KR Molloy, BT Chait, MP Rout, D Fenyö, TH Jensen, I Altukhov, J LaCava. 2020. Affinity proteomic dissection of the human nuclear cap-binding complex interactome. Nucleic Acids Research. gkaa743
  • Baldwin, ET, T van Eeuwen, D Hoyos, A Zalevsky, EP Tchesnokov … KH Burns, M Götte, MP Rout, E Arnold, BD Greenbaum. DL Romero, J LaCava, MS Taylor. 2024. Structures, functions, and adaptations of the human LINE-1 ORF2 protein. Nature. 626, 194–206
  • Nielsen, MI, JC Wolters, OG Rosas Bringas, H Jiang, LH Di Stefano, M Oghbaie, S Hozeifi, MJ Nitert, A van Pijkeren, M Smit, L ter Morsche, A Mourtzinos, V Deshpande, MS Taylor, J LaCava. 2025. Targeted detection of endogenous LINE-1 proteins and ORF2p interactions. Mobile DNA. 16:3