CV Science

Giuseppina Caligiuri Research Director (DR1) Inserm, MD, PhD, Cardiovascular Immunobiology

Course and current status

Research Director (DR1) at INSERM (U1148, head of team 1 www.lvts.fr)

Clinical Fellow in Cardiology (PATT, Univ. Hospital Bichat/Beaujon, Paris, FR)

Scientific founder and consultant at Tridek One Therapeutics

>1998  Immunopathology and immunomodulation of atherosclerotic diseases

    Clinical studies in patients (clinical evaluation, peripheral blood and tissue analysis)

Experimental studies in mice (survival surgery, immunointervention, tissue analysis)

>2004  Immunoregulation in atherothrombosis, rheumatoid arthitis and multiple sclerosis

    Clinical studies in patients (clinical evaluation, diagnostic tools and prognostic studies)

 Experimental studies in mice (pre-clinical and molecular evaluation of candidate drugs)

2006  Research Leading Habilitation (HDR, Faculté de Médecine, Paris V, FR)

« Role of CD31 in atherosclerosis physiopathology »

2002   First Class Researcher (CR1, INSERM, Paris FR)

« The immunopathology of vascular remodeling »

2000   Doctor in Science (Karolinska Institute, Stockholm, SE and Univ. Paris 7, FR)

           « The immune response in atherosclerosis and acute coronary syndromes »

1997    Post-graduate Specialization in Cardiology (Catholic University, Rome, IT)

         « Immune-inflammatory markers in patients with coronary artery disease »

1993     Doctor in Medicine and Surgery (Catholic University, Rome, IT)

1987     Baccalaureate in Sciences (“Filolao” High School, Crotone, IT)

Research animation activities

Scientific summary

My original research area focuses on the role of CD31 as a co-signalling receptor involved in the regulation of cardiovascular biology and homeostasis maintenance. The concept has disrupted a long-lasting dogma as CD31 has widely been considered as an adhesion molecule with proinflammatory functions by other researchers in this field.

My own research subject on CD31 as an independent scientists has started with the seminal discovery of the immunoregulatory co-signalling role exerted by CD31, which is lost upon its cleavage at the cell surface (J Immunol 2010). This discovery opened two clinical applications: the soluble portion has a very interesting diagnostic/prognostic value in cardiovascular and inflammatory diseases. On the other hand, since the juxtamembrane sequence of CD31 remains on activated cells we used peptides targeting this segment as the first of a new class of immunomodulatory drugs, acting by sustaining the activity an endogenous regulatory co-receptor instead of suppressing a given immune effector pathway (Cardiovasc Res 2012, PNAS 2014, J Autoimmun 2015).

The potential clinical use for CD31 agonist peptides could extend beyond systemic treatment: the homeostatic function of CD31 agonists could prevent the reaction of the vascular and blood cells against endovascular devices, and improve the outcome of arterial stenting (hampered by the reaction of the vascular and blood cells at the site of implantation). Thus we are developing a CD31-mimetic coating suitable for clinical-grade endovascular devices (PhD thesis published in 2018).

Due to CD31’s putative involvement in the transduction of mechanic stimuli, its regulatory role is of outmost importance for the control of inflammation and thrombosis affecting the cardiovascular tissue itself, such as in the case of dissected arteries, which must conduct the hemostatic and inflammatory phases of the wound healing process while being subjected to a persistent, cyclic mechanic stress (J Am Coll Cardiol 2018). This led me to reconsider the role of inflammation in the pathogenesis of atherosclerosis and of its complications: the deleterious role of the inflammatory response results from a defective control of the biologic processes involved in the healing of the iterative wounds, caused by the high hemodynamic, mechanic stress exerted on the tissue of our circulatory system (Eur Heart J). My most recent interest has therefore been turned toward the role of CD31 in the control of wound healing of the heart after a myocardial infarction. (PhD thesis, defended in 2019).

My work of the last 10 years has raised a considerable interest in cardiovascular research and I have been invited to write comprehensive reviews to replace the role of CD31 in the mechanotransduction and immunometabolic involved in cardiovascular pathophysiology Cardiovascular Research 2019) as well as to illustrate the rationale behind the therapeutic potential of CD31-targeting drugs for the treatment of atherosclerosis (Circulation Research 2020).

More recently, I have focused on the application of CD31 targeting therapies to endovascular devices (Stroke 2021 and Eur H J 2021) as well as exploring other sorts of bioactive coating to improve the efficacy of thrombectomy devices.

In summary, since my appointment as Research Director in 2009, I have successfully conducted original research projects resulting from my discovery of CD31 cleavage at the interface between blood and vessels. These projects range from basic research to clinical application and have driven several students and colleagues to get working with me in my specific research field. It was therefore natural that I became responsible for the Cardiovascular Immunobiology team in my host laboratory. My capacity for concretization is evident from the funding, industrial partnerships, publications, and development actions that I have undertaken (9 patents filed, including 5 granted under license; I am the scientific founder of the company ‘TRIDEK-One’, which means CD31 in Esperanto-English. My expertise is recognized at the national level (member of the board of the Experimental Cardiovascular Research Group and "cardiovascular" expert of the scientific committee of National Institute of Physiopathology), and at the international level (member of the scientific committee of EAS and representative for Europe of the International Society of Atherosclerosis - IAS). My experience has earned me growing responsibilities in postgraduate education (pedagogical manager of the teaching program "Circulation" and of the Master 2 “Biocoeur” for the University of Paris). I assume increasing responsibilities in the animation of research and the dissemination of knowledge also at the international level: I have co-edited the textbook "Vascular Biology" of the European Society of Cardiology and am associate editor of 3 important journals in the field (Cardiovascular Research, ATVB, and Atherosclerosis). Finally, I have been invited to organize the Summer School in Basic Science of the European Society of Cardiology for two consecutive editions and, based on the positive appreciation of the past attending students and organizers, I have been nominated Director of the forthcoming 2021 Summer School edition.

Bibliometric indicators

123 Publications sur PubMed, H-Index 41

https://publons.com/researcher/2399936/giuseppina-caligiuri/

https://orcid.org/0000-0003-4973-2205