Unit of Molecular Mechanisms of Cardiovascular Remodeling

Head of the Unit

Nuno Guimaraes Camboa, PhD

The Molecular Mechanisms of Cardiovascular Remodeling Research Unit is dedicated to investigating the cellular and molecular mechanisms that drive fibrotic remodeling of the heart, with the ultimate goal of developing novel anti-fibrotic therapies.

Cardiac fibrosis disrupts the normal structure and function of the myocardium by creating both mechanical and biochemical barriers to contractility. It is a hallmark of most forms of heart failure and contributes significantly to disease progression and adverse clinical outcomes. Despite its major clinical impact, effective anti-fibrotic treatments are still lacking, making cardiac fibrosis a significant unmet medical need and a key priority in cardiovascular research.

To address this challenge, the Unit adopts an integrated research approach that combines advanced microscopy with state-of-the-art omics technologies to identify the key molecular regulators—typically transcription factors and cytokines—that orchestrate fibrotic processes. These targets are subsequently investigated for their therapeutic potential using pharmacological and gene therapy strategies, with the aim of translating mechanistic discoveries into clinically relevant innovations.

By uncovering the regulatory networks that control fibrotic remodeling, the Unit seeks to develop targeted interventions capable of preventing or reversing pathological fibrosis, ultimately preserving cardiac function and improving outcomes for patients with cardiovascular disease.

Selected Projects

  • To gain a deeper understanding of the mechanisms underlying cardiac fibrosis and to develop innovative strategies to combat it, our research projects are organized around three main areas:

    1. Identification of Novel Therapeutic Targets

    We employ state-of-the-art next-generation sequencing (NGS) technologies—including single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics—to map the diverse subpopulations of cardiac fibroblasts and identify the molecular regulators that drive the various processes involved in fibrosis.

    2. Understanding Fibroblast Heterogeneity

    Not all fibroblasts are alike. We investigate how distinct fibroblast subpopulations contribute to fibrotic remodeling of the heart by combining lineage-tracing approaches with advanced microscopy techniques. These studies provide critical insights into the cellular dynamics and functional specialization of fibroblasts during disease progression.

    3. Development of Novel Biological Therapies

    Because cardiac fibroblasts are notoriously difficult to target using conventional gene therapy vectors, we are exploring innovative delivery strategies, including engineered viral serotypes with enhanced tissue tropism and lipid nanoparticle-based platforms. These approaches aim to improve the specificity and efficiency of therapeutic delivery to fibroblast populations within the heart.

    Our ultimate goal is to translate these discoveries into new therapeutic opportunities to prevent or limit cardiac fibrosis, preserve cardiac function, and improve patient outcomes.

best publications in the last three years

    • Increasing mononuclear diploid cardiomyocytes by loss of E2F7/8 fails to improve cardiac regeneration post infarct. Yu Z, Zhang L, Cattaneo P, Guimaraes-Camboa N, Fang X, Gu Y, Peterson K, Bogomolovas J, Cuitino C, Leone G, Chen J, and Evans SM. Circulation, 147(2):183-186 (2022).
    • DOT1L regulates chamber-specific transcriptional networks during cardiogenesis and mediates postnatal cell cycle withdrawal. Cattaneo P, Hayes MGB, Baumgarten N, Hecker D, Peruzzo S, Aslan GS, Kunderfranco P, Larcher V, Zhang L, Contu R, Fonseca G, Spinozzi S, Chen J, Condorelli G, Dimmeler S, Schulz MH, Heinz S, Guimaraes-Camboa N and Sylvia M. Evans. Nature Communications 13(1):7444 (2022).
    • Myocardial matrix hydrogel acts as a reactive oxygen species scavenger and supports a proliferative microenvironment for cardiomyocytes. Wang R.M., Mesfin J.M., Hunter J., Cattaneo P., Guimarães-Camboa N., Braden R.L., Luo C., Hill R.C., Dzieciatkowska M., Hansen K.C., Evans S.M., Christman K.L. Acta Biomaterialia 152, 47-59 (2022).
    • Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors. Lenti E., Genovese L., Bianchessi S., Maurizio A., Sain S.B., Lillo A., Mattavelli G., Harel I., Bernassola F., Hehlgans T., Pfeffer K., Crosti M., Abrignani S., Evans S.M., Sitia G., Guimarães-Camboa N., Russo V., van de Pavert S.A., Garcia-Manteiga J.M., Brendolan A. Immunity 55 (4), 606-622 (2022).
    • Parallel lineage-tracing studies establish fibroblasts as the prevailing in vivo adipocyte progenitor. Cattaneo P, Mukherjee D, Spinozzi S, Zhang L, Larcher V, Stallcup WB, Kataoka H, Chen J, Dimmeler S, Evans SM and Guimaraes-Camboa N.Cell Reports: 571-582.e2 (2020).

Staff

  • Francesca Andriani, MSc

    Erica Pedrazzini, MSc