centro biotecnologie avanzate

ANTONIO DE FLORA
Brief Curriculum Vitae

Born in Genova (Italy), February 7, 1940. MD with honours (University of Genova, 1964). LD (=PhD) in Biochemistry (1967) and in Applied Biochemistry (1969). Full Professor of Biochemistry at the Medical School of the University of Genova (1973- ). Director (1981-1990) of the Institute of Biochemistry, University of Genova. Coordinator of the Biology Area of the University of Genova (1995-2001). Delegate of the Genova University at the Interuniversity Consortium on Biotechnology (1987- ), Chairman of the Scientific Committee of Siena Research Consortium (1992-2003), national expert at Italian Ministries of University and Scientific Research (M.U.R.) and of Economic Development (M.A.P.) on programmes of industrial research, national delegate at COBIOTECH (ICSU, Paris). President of the Scientific Committee of the Advanced Biotechnology Center (ABC, Genova, 2003-2006). President of the Advanced Biotechnology Center (Genova, 2006- ). Member of several boards and committees of National Research Council (C.N.R.) institutions, consultant of E.U. and M.U.R. in the biotechnological area, member of the Italian Board for Biotechnology (1985-1990), member of the International Affairs of M.U.R. (1988-1993), President of the Italian Society of Biochemistry and Molecular Biology (2009- ). Director, C.N.R. Target Projects on "Biotechnology and Bioinstrumentation" (1988-96) and "Biotechnology" (1998-2006). City of Genova Prize for Science (1997). Editor, Biotechnology and Applied Biochemistry (1990-2003), member of the Editorial Board, Journal of Biological Chemistry (2008- ), current referee of many international journals of biochemistry and biotechnology. Consultant of several international universities and research institutions for career promotion and for research programs. Consultant of prize-awarding international boards (including Nobel and Kyoto prizes). Recipient of several research grants from national and international agencies.
Interests of A. De Flora have been ranging over several fields of biochemistry and biotechnology, including basic enzymology, general features of carbohydrate metabolism and pentose phosphate pathway, structural, functional and regulatory properties of glucose 6-P dehydrogenase (G6PD), mechanisms of G6PD deficiency, oxidative hemolysis, enzymology and metabolis of methylpentoses, mechanisms of Leukocyte Adhesion Deficiency type II, synthesis of pro-drugs, construction of engineered (enzyme- , antigen-, and pro-drug-loaded) erythrocytes as carriers and circulating bioreactors.
In the last 15 years, his interests have been focusing on cellular mechanisms of interaction between second messengers and intracellular calcium homeostasis. A. De Flora and his Colleagues have identified and elucidated the topological paradox of the CD38/NAD yclic ADP-ribose (cADPR)/intracellular calcium ([Ca]i)system. This paradox was explained in Genova by addressing and demonstrating a number of autocrine and paracrine mechanisms whereby NAD and cADPR undergo a subcellular and an extracellular trafficking by means of redundant transmembrane (di)nucleotide transporters. As a consequence of this trafficking, cells can modify their [Ca]i and regulate accordingly a number of key, calcium-related functions. Cellular processes investigated by A. De Flora and Colleagues are centered on: i) on the functional crosstalk of NAD, cyclic-ADP ribose (cADPR), ADP-ribose (ADPR), NADP and NAADP, ii) on sites (either ectocellular or subcellular) of their enzymatic generation, iii) on their transport across both concentrative and equilibrative transporters, iv) on selected extracellular and intracellular receptors thereof. These signal metabolites, whose interplay regulates calcium-related cell functions and processes, are investigated in several mammalian cells and cell lines. The general goal of this research line is to identify and characterize some still poorly defined codes of intercellular communication, perspectively suggesting new molecular targets to be exploited for the development of innovative drugs.
Studies performed in A. De Flora's lab opened the way to three new areas of investigation still based on ADP-ribosyl cyclases (ADPRCs) and on their impact on calcium-dependent cell functions.
The first one concerns two novel adenine homodinucleotides, generated by a number of ADPRCs including the human ectoenzyme CD38, that contain two unusual N-glycosidic bonds and affect intracellular calcium and cell proliferation in distinctive ways.
The second area is related to the recent that the plant hormone Abscisic acid (ABA) is synthesized also by human cells. Specifically, in human granulocytes, ABA is produced novo following exposure to physical and chemical stimuli and activates phagocytosis, migration, generation of ROS and NO through a signalling cascade triggered by binding of ABA to a PTX-inhibitable receptor/G protein complex and involving protein kinase A (PKA) activation, PKA-mediated phosphorylation and activation of the ADPRC CD38, overproduction of cADPR and increase of the [Ca]i. Thus, ABA behaves as an endogenous pro-inflammatory cytokine and evidences are emerging for such a surprising role being played by ABA in other human cells and cell systems.
Finally, the third related topic concerns the involvement of extracellular NAD and NAADP as agonists of the human P2Y11 purinergic receptor in human granulocytes in which both dinucleotides trigger functional stimulation through a signalling pathway that involves cADPR and increased [Ca]i. A. De Flora's laboratory is pursuing the aim to achieve advanced knowledge on a stimulating field of "ectobiochemistry" where the functional interaction among several players, i.e. ectoenzymes, receptors, transporters, channels and signal-transducing systems can lead to a fine regulation of fundamental, calcium-related cell functions.
De Flora has published over 200 papers on international journals and book chapters. He is the author of the chapter on "Biochemistry and Bioenergetics", Treccani National Encyclopedia, (Appendix 2000) and of the chapter on “Biotechnologies”, volume The Big Science, Science History of the Treccani National Institute. Inventor of 9 patents.