Projects per year
Cell biology and immunology of neutrophils
Neutrophils are essential immune cells with important roles in defence against pathogens. They rapidly migrate to sites of infection and kill microbes by phagocytosis, ROS production, degranulation and release of neutrophil extracellular traps (NETs). Absence of neutrophils results in a complete inability of the organism to ward off pathogens. Excessive or dysregulated neutrophil responses, on the other hand, are destructive and contribute to pathology in malaria, autoimmunity and cancer. Mechanisms that fine-tune neutrophil responses are therefore critical for health.
We study how cell cycle and DNA repair proteins regulate neutrophil effector functions. We propose the hypothesis that cell cycle proteins have non-canonical roles in inflammation and that their dysregulation leads to dysfunctional neutrophil responses. Our work also aims to elucidate the function of cell cycle factors in post-mitotic cells.
We want to understand how neutrophils are regulated at the molecular level and to use these insights to interrogate their function in immunity and inflammation. We also aim to develop therapies targeting neutrophils in malaria, a devastating disease that affects millions of people in developing countries.
Our research spans cell biology and immunology. We use molecular biology techniques such as CRISPR/Cas9 knockout to characterize genes regulating human neutrophil behavior. We also use various disease models and patient samples to investigate neutrophils in vivo.
One area of focus is mechanism and function of neutrophil extracellular traps (NETs). NETs consist of extruded chromatin with antimicrobial and immunostimulatory properties. They are released via an active process called NETosis and are proposed to trap microbes as well as signal to the rest of the immune system.
Our goal is to propose targets for therapies in inflammatory diseases (including malaria, autoimmunity and cancer), as well as to discover ways to boost neutrophil microbicidal activity in settings such as immunodeficiency and antimicrobial resistance.
- 1 Similar Profiles
1/09/18 → 31/08/23
1/03/22 → 1/04/22
Constantinescu, A-E., Mitchell, R. E., Zheng, J., Bull, C. J., Timpson, N. J., Amulic, B., Vincent, E. E. & Hughes, D. A., 29 Jan 2022, In: Human Genomics. 16, 1, 14 p., 3.
Research output: Contribution to journal › Article (Academic Journal) › peer-reviewOpen AccessFile43 Downloads (Pure)
Rice, C. M., Lewis, P., Ponce-Garcia, F. M., Gibbs, W., Cela, D., Hamilton, F., Arnold, D., Hyams, C., Oliver, E., Barr, R., Goenka, A., Davidson, A., Wooldridge, L., Finn, A., Rivino, L. & Amulic, B., 1 Mar 2022, In: bioRxiv.
Research output: Contribution to journal › Article (Academic Journal) › peer-review
Intravascular administration of soluble SARS-CoV-2 Spike protein triggers non-infective heart and lung inflammation and vascular pericytes rarefaction in healthy miceAvolio, E., Carrabba, M., Gu, Y., Tsang, C. T. W., Amulic, B., Savitri, E. R., Still, K., Maggiani, F., Thomas, A. C., Groves, S. J., Gupta, K., Berger, I., Kafienah, W., Caputo, M. & Madeddu, P. R., 27 Jun 2022, (Accepted/In press) European Heart Journal Supplements.
Research output: Chapter in Book/Report/Conference proceeding › Conference Contribution (Conference Proceeding)