Research Groups

Macromolecules and Interactomes

The Laboratory of Macromolecules and Interactomes focuses, broadly, on characterizing the contributions of dysregulated macromolecular interactions to human diseases. To achieve this, we use a combination of protein-centric biochemical, ‘omics, and computational approaches. We maintain a special focus on charting interactions important to human RNA processing and those contributing to the molecular physiology of human LINE-1 retrotransposons. For more details, see the ‘info’ tab, below.

 We believe that Jacques Monod said it best:

 We are all aware of the fact that any phenomenon, any event, or for that matter, any “knowledge,” any transfer of information implies an interaction, and that no interaction may take place without an alteration, an evolution of the interacting system.
– Proceedings of the 11th Nobel Symposium, Södergarn, Lidingö, Sweden, Aug. 1968.

  • People
  • Info
  • Publications
  • John LaCava Visit

    Group Leader of the Laboratory of Macromolecules and Interactomes

    Research fields

    Human Interactomics, L1 Retrotransposons, and RNA Processing

    Postdoctoral Fellows
    Mohammed Hanzala
    PhD Students
    Omar Rosas Bringas
    Shaoshuai Xie
  • Improving Methods and Technology for Interactome Analyses

    Proteins and the macromolecular complexes they form are the effectors of cell biology. Studying cell biology therefore requires the ability to isolate distinct proteins along with other constituents of their associated macromolecules. Affinity capture techniques have greatly facilitated the discovery, purification, and characterization of endogenous protein complexes. These techniques leverage reagents able to target and capture proteins of interest assembled with physiological binding partners, from cell extracts. Although affinity capture has matured steadily as an approach, many technical shortcomings still limit its efficacy in the retrieval of intact, endogenous macromolecules. We address these challenges and develop mass spectrometry-based, affinity proteomic techniques for interactome mapping. We place special emphasis on approaches that also enable downstream structural and biochemical studies of purified macromolecules.


    Characterizing Human L1 Retrotransposons

    Long Interspersed Element 1 (LINE-1, L1) is a retrotransposon. As a result of its “copy and paste” method of proliferation, L1 activity has contributed a large proportion of DNA to the human genome (including those sequences mobilized by L1, such as Alus). Since the insertion of new DNA sequences into the genome is inherently mutagenic, understanding the lifecycle of L1 is crucial to understanding human genome dynamics and cell biology. L1 DNA proliferates through an RNA intermediate whose protein products bind the L1 RNA to form a ribonucleoprotein (RNP) complex. L1 RNPs also co-opt and contend with a variety of host factors that facilitate or repress L1’s ability to reach the chromatin and reintegrate into the genome. Thus, different subpopulations of L1s consist of different assortments of constituents, depending both on the subcellular compartment and on the pathway being traversed (proliferation or repression). We develop methods to expand our breadth of knowledge concerning the L1 interactome, and we study the structural and biochemical properties of L1 RNPs.


    Characterizing Human RNA Processing

    The RNA exosome is a macromolecular complex comprising endo- and exoribonucleases. It is an essential component of the RNA-metabolism machinery in eukaryotes, functioning in the accurate processing of precursors to mature RNAs and in RNA turnover. The exosome is active in both the nucleus and the cytoplasm, and depending on the subcellular compartment where the exosome is active, the constituents of the complex and associated adapters vary – yielding a collection of distinctive subpopulations in vivo. We focus on the discovery, purification, and characterization of RNA exosomes, their adapter complexes, and related macromolecules participating in post-transcriptional gene regulation.

    • Winczura K, Domanski M, LaCava J. (2020) Affinity Proteomic Analysis of the Human Exosome and Its Cofactor Complexes. Methods in Molecular Biology.  
    • Dou Y, Kalmykova S, Pashkova M, Oghbaie M, Jiang H, Molloy KR, Chait BT, Rout MP, Fenyö D, Jensen TH, Altukhov I, LaCava J. (2020) Affinity proteomic dissection of the human nuclear cap-binding complex interactome. Nucleic Acids Research.  
    • Dou Y, Barbosa I, Jiang H, Iasillo C, Molloy KR, Schulze WM, Cusack S, Schmid M, Le Hir H, LaCava J, Jensen TH. (2020) NCBP3 positively impacts mRNA biogenesis. Nucleic Acids Research.
    • Carter V, LaCava J, Taylor MS, Liang SY, Mustelin C, Ukadike KC, Bengtsson A, Lood C, Mustelin T. (2020) High Prevalence and Disease Correlation of Autoantibodies Against p40 Encoded by Long Interspersed Nuclear Elements in Systemic Lupus Erythematosus. Arthritis Rheumatology.  
    • Ardeljan D, Wang X, Oghbaie M, Taylor MS, Husband D, Deshpande V, Steranka JP, Gorbounov M, Yang WR, Sie B, Larman HB, Jiang H, Molloy KR, Altukhov I, Li Z, McKerrow W, Fenyö D, Burns KH, LaCava J. (2020) LINE-1 ORF2p expression is nearly imperceptible in human cancers. Mobile DNA.  
    • Taylor MS, Altukhov I, Molloy KR, Mita P, Jiang H, Adney EM, Wudzinska A, Badri S, Ischenko D, Eng G, Burns KH, Fenyö D, Chait BT, Alexeev D, Rout MP, Boeke JD & LaCava J. (2018) Dissection of affinity captured LINE-1 macromolecular complexes. eLife.
    • Domanski M, Upla P, Rice WJ, Molloy KR, Ketaren NE, Stokes DL, Jensen TH, Rout MP & LaCava J. (2016) Purification and Analysis of Endogenous Human RNA Exosome Complexes. RNA.
    • Hakhverdyan ZM, Domanski L. Hough AA, Oroskar AR, Oroskar DJ, Dilworth KR, Molloy V, Sherman JD, Aitchison BT, Chait, Jensen TH, Rout MP & LaCava J. (2015) Rapid, Optimized Interactomic Screening. Nature Methods.  
    • Taylor MS, LaCava J, Mita P, Molloy KR, Huang CR, Li D, Adney EM, Jiang H, Burns KH, Chait BT, Rout MP, Boeke JD & Dai.L. (2013) Affinity proteomics reveals human host factors implicated in discrete stages of LINE-1 retrotransposition. Cell.
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