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
Emerging Lines of Investigation (select examples)
- PARP14 interactomes and roles in inflammatory diseases
- Contributions of O-mannosylation to E-cadherin interactomes
- Mass photometry as an affinity proteomics tool
- LINE-1 retrotransposons in aging and neurodegeneration
- LINE-1 retrotransposons in Systemic Lupus Erythematosus (SLE)
- LINE-1 retrotransposons in colorectal cancer
Major Funding (≥ $50k, previous 5 years)
- The National Institute on Aging, Research Program Grant – 2022
- Ribon Therapeutics Inc., Sponsored Research Agreement – 2022
- Interrogating PARP14 interactomes in search of mechanisms of action
- Robertson Therapeutic Development Fund, Proof-of-Concept Grant – 2022
- LINE-1 retrotransposons as drivers of neuroinflammation and Alzheimer’s disease
- Health Holland & ROME Therapeutics Inc., Public Private Partnership – 2020
- Robertson Therapeutic Development Fund, Proof-of-Concept Grant [continuation] – 2020
- Diagnostic detection of L1 retrotransposons, a newly recognized hallmark of cancer
- Health Holland & Refeyn Ltd., Public Private Partnership – 2020
- The National Institute of General Medical Science, Research Program Grant Supplement – 2020
- Robertson Therapeutic Development Fund, Proof-of-Concept Grant – 2019
- Diagnostic detection of L1 retrotransposons, a newly recognized hallmark of cancer
- Worldwide Cancer Research, Project Grant – 2019
- The National Institute of General Medical Science, Research Program Grant – 2017
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.