Research Profile

John LaCava, Ph.D.

Group Leader, Associate Professor, European Research Institute for the Biology of Ageing
Research Associate Professor, The Rockefeller University
Managing Director, B13LOGY LLC

John LaCava earned an A.S. degree from Massachusetts Bay Community College in Biotechnology (1998) and completed his B.S. degree in Biotechnology from the University of California, Davis (2000). He subsequently earned his Ph.D. in Molecular Genetics (2005) from The University of Edinburgh, Scotland, where he studied mechanisms of post-transcriptional gene regulation with Prof. David Tollervey. Thereafter, John trained in structural proteomic research methods within the Mass Spectrometry of Biomacromolecules group at the University of Amsterdam; and as an EMBO long term post-doctoral fellow, he studied pre-mRNA splicing regulation at the Centre for Genomic Regulation in Barcelona, Spain. In 2008, John returned to the USA to join the Laboratory of Cellular and Structural Biology at The Rockefeller University. Working with Profs. Michael Rout, Brian Chait, and others in the NIH-funded National Center for Dynamic Interactome Research, John focussed on developing methods to improve protein interactions studies. In 2016 John was promoted to the rank of Research Assistant Professor at The Rockefeller University and also joined the NIH-funded Center for Systems Biology of Retrotransposition, earning him a joint appointment as Visiting Assistant Professor at the Institute for Systems Genetics, NYU Langone Health. In 2019 John was promoted to Research Associate Professor at The Rockefeller University, and was recruited to join European Research Institute for the Biology of Ageing (at the University Medical Center Groningen) as a Group Leader and Associate Professor, where he heads the Laboratory of Macromolecules and Interactomes.

John’s group develops biochemical and ‘omics methods to study the contributions of dysregulated macromolecular interactions to human diseases, including those related to ageing. Among these, the group study the molecular (patho)physiology of LINE-1 ribonucleoproteins in cancer and ageing.

Emerging Lines of Investigation (select examples)

Major Funding (≥ $50k, previous 5 years)

2023

CCDC88B interacts with RASAL3 and ARHGEF2 and regulates dendritic cell function in neuroinflammation and colitis. Communications Biology. DOI: 10.1038/s42003-023-05751-9

Multi-parameter screening optimizes immunoprecipitation. BioTechniques. Accepted (coming soon)

Structures, functions, and adaptations of the human LINE-1 ORF2 protein. Nature. DOI: 10.1038/s41586-023-06947-z 

Multiple RNA-binding proteins associated with long interspersed element-1 encoded ORF1p are targeted by the autoimmune response in systemic lupus erythematosus. Journal of Cellular and Molecular Immunology. DOI: 10.46439/immunol.2.022

Consequences of a telomerase-related fitness defect and chromosome substitution technology in yeast synIX strains. Cell Genomics. DOI: 10.1016/j.xgen.2023.100419

Ultrasensitive detection of circulating LINE-1 ORF1p as a specific multi-cancer biomarker. Cancer Discovery. DOI: 10.1158/2159-8290.CD-23-0313

Expression of L1 retrotransposons in granulocytes from patients with active systemic lupus erythematosus. Mobile DNA. DOI: 10.1186/s13100-023-00293-7


2022

LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint. PNAS. DOI: 10.1073/pnas.2115999119

Targeting DNA topoisomerases or checkpoint kinases results in an overload of chaperone systems, triggering aggregation of a metastable subproteome. eLife. DOI: 10.7554/eLife.70726


2021

IgG and IgA autoantibodies against L1 ORF1p expressed in granulocytes correlate with granulocyte consumption and disease activity in pediatric systemic lupus erythematosus. Arthritis Research & Therapy. DOI: 10.1186/s13075-021-02538-3


2020

Affinity proteomic dissection of the human nuclear cap-binding complex interactome. Nucleic Acids Research. DOI: 10.1093/nar/gkaa743

NCBP3 positively impacts mRNA biogenesis. Nucleic Acids Research. DOI: 10.1093/nar/gkaa744

National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level: Interrogation of Premalignant Lesions. Journal of Proteome Research. DOI: 10.1021/acs.jproteome.0c00021

LINE-1 ORF2p expression is nearly imperceptible in human cancers. Mobile DNA. DOI: 10.1186/s13100-019-0191-2


2019

To the editor in reply to Dr. Crow’s letter. Arthritis Rheumatology. DOI: 10.1002/art.41104

High prevalence and disease correlation of autoantibodies against p40 encoded by long interspersed nuclear elements (LINE-1) in systemic lupus erythematosus. Arthritis & Rheumatology. DOI: 10.1002/art.41054

Identification of RNase-sensitive LINE-1 Ribonucleoprotein Interactions by Differential Affinity Immobilization. Bio-protocol. DOI: 10.21769/BioProtoc.3200

RNA Binding Proteins as Regulators of Retrotransposon‐Induced Exonization. Bioessays. DOI: 10.1002/bies.201800263


2018

Targeting the CALR Interactome in Myeloproliferative Neoplasms. JCI Insight. DOI 10.1172/jci.insight.122703

Polycomb Complexes Associate with Enhancers and Promote Oncogenic Transcriptional Programs in Cancer through Multiple Mechanisms. Nature Communications. DOI: 10.1038/s41467-018-05728-x

Functions of unconventional mammalian translational GTPases GTPBP1 and GTPBP2. Genes & Development. DOI: 10.1101/gad.314724.118

Dissection of affinity captured LINE-1 macromolecular complexes. eLife. DOI: 10.7554/eLife.30094

LINE-1 protein localization and functional dynamics during the cell cycle. eLife. DOI: 10.7554/eLife.30058

Characterizing ZC3H18, a multi-domain protein at the interface of RNA production and destruction decisions. Cell Reports. DOI: 10.1016/j.celrep.2017.12.037


2017

Tumor suppressor NPRL2 induces ROS production and DNA damage response. Scientific Reports. DOI: 10.1038/s41598-017-15497-0

The Polycomb group protein CBX6 is an essential regulator of embryonic stem cell identity. Nature Communications. DOI: 10.1038/s41467-017-01464-w

RNA Degradation Assay Using RNA Exosome Complexes, Affinity-purified from HEK-293 Cells. Bio-protocol. DOI: 10.21769/BioProtoc.2239

Affinity Purification of the RNA Degradation Complex, the Exosome, from HEK-293 Cells. Bio-protocol. DOI: 10.21769/BioProtoc.2238


2016

Purification and Analysis of Endogenous Human RNA Exosome Complexes. RNA. DOI: 10.1261/rna.057760.116

Protein complex affinity capture from cryomilled mammalian cells. Journal of Visualized Experiments. DOI: 10.3791/54518


2015

Rapid, Optimized Interactomic Screening. Nature Methods. DOI: 10.1038/nmeth.3395

Affinity proteomics to study endogenous protein complexes: Pointers, pitfalls, preferences and perspectives. BioTechniques. DOI: 10.2144/000114262


2014

Expression and detection of LINE-1 ORF-encoded proteins. Mobile Genetic Elements. DOI: 10.4161/mge.29319


2013

The human cap-binding complex is functionally connected to the nuclear RNA exosome. Nature Structural & Molecular Biology. DOI: 10.1038/nsmb.2703

Affinity proteomics reveals human host factors implicated in discrete stages of LINE-1 retrotransposition. Cell. DOI: 10.1016/j.cell.2013.10.021

Improved native isolation of endogenous Protein A-tagged protein complexes. BioTechniques. DOI: 10.2144/000114012


2012

Improved methodology for the affinity isolation of human protein complexes expressed at near endogenous levels. BioTechniques. DOI: 10.2144/000113864


2006

RNA-quality control by the exosome. Nature Reviews Molecular Cell Biology. DOI: 10.1038/nrm1964


2005

RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell. DOI: 10.1016/j.cell.2005.04.029

2023

Affinity-Based Interactome Analysis of Endogenous LINE-1 Macromolecules. In M.R. Branco & A. de Mendoza Soler (Eds.), Transposable Elements: Methods and Protocols. Springer. DOI: 10.1007/978-1-0716-2883-6_12


2020

The Eukaryotic Exosome: Methods and Protocols. Methods in Molecular Biology Series (Springer). Vol: 2062. Eds. LaCava, J & Vaňáčová, Š. DOI: 10.1007/978-1-4939-9822-7

Affinity Proteomic Analysis of the Human Exosome and Its Cofactor Complexes. In J. LaCava & Š. Vaňáčová (Eds.), The Eukaryotic RNA Exosome: Methods and Protocols. Springer. DOI: 10.1007/978-1-4939-9822-7_15


2016

Protein Complex Purification by Affinity Capture. In B. Andrews, C. Boone, T. Davis, & S. Fields (Eds.), Budding Yeast: A Laboratory Manual. Cold Spring Harbor Laboratory Press. DOI: 10.1101/pdb.top077545. Includes 3 companion protocols: DOI: 10.1101/pdb.prot087932; DOI: 10.1101/pdb.prot087940; DOI: 10.1101/pdb.prot087957

Characterization of L1-RNPs. In J.L. Garcia (Ed.), Transposons and Retrotransposons: Methods and Protocols. Springer. DOI: 10.1007/978-1-4939-3372-3_20

2022

(PENDING) Ultrasensitive Assays for Detection of ORF1p in Biofluids. U.S. Patent Application No. 63/423,696.

2015

Apparatus and Method for Parallel Collection and Analysis of the Proteome and Complex Compositions. US Patent No. 9,084,994.

Cancer cells co-evolve with retrotransposons to mitigate viral mimicry. DOI: 10.1101/2023.05.19.541456

Repeats Mimic Immunostimulatory Viral Features Across a Vast Evolutionary Landscape. DOI: 10.1101/2021.11.04.467016

Complex+: Aided Decision-Making for the Study of Protein Complexes. DOI: 10.1101/744656