According to
Google Scholar, Giulio Superti-Furga has published more than 260 manuscripts that have been collectively cited > 47,000 times, reflected by an
h-index of 100. The article "Functional organization of the yeast proteome by systematic analysis of protein complexes" by Gavin, AC*, 36 authors, Superti-Furga G* (* shared correspondence),
Nature 2002 has been cited almost 6,000 times. As scientific director of CeMM, Giulio Superti-Furga promoted a unique mode of super-cooperation, connecting biology with medicine, experiments with computation, discovery with translation, and science with society and the arts. His research activities cover a broad set of disciplines from
structural biology to clinical diagnostics, from
immunology to
metabolism, from atomic resolution to network structures. His previous work focused on immunity and metabolism combined with the selective uptake of molecules and integrating it with drug action. Recent research interests of Giulio Superti-Furga include novel ways to create functional
personalized medicine approaches and understanding the role of the human
membrane transporters in pathophysiology and drug discovery.
Metabolism and regulation of metabolite concentration Membrane transporters can be considered the managers of the interface between chemistry and biology and between organisms and their environment.
Membrane transporters, and their roles in metabolism, drug transport and signaling are being investigated heavily in Giulio Superti-Furga's laboratory. As they are overall a large and neglected gene family in humans, Giulio Superti-Furga proposed to intensify and coordinate research on the largest group of membrane transporters in the human genome, the solute carrier (SLC) superfamily. A large part of Giulio Superti-Furga's laboratory in working in the RESOLUTE and REsolution projects supported by the
IMI, the
EU and the
EFPIA. RESOLUTE and REsolution are private-public partnerships co-led by Giulio Superti-Furga and Claire Steppan (
Pfizer). On one hand, RESOLUTE's goal is to intensify research on
SLCs worldwide and to establish them as a novel target class for medical research. On the other hand, The REsolution project focuses on human
genetic variations in transporters and their link to human disease, and it links the RESOLUTE knowledge to physiology and disease through human genetics. To that end, RESOLUTE and REsolution are empowering the scientific community with biological tools and data sets for SLC research, developing robust transport assays, and compiling the information in the SLC knowledgebase. Besides the
systems biology approach used in RESOLUTE / REsolution for the whole family of SLCs, Giulio's laboratory also focuses on individual transporters. His lab showed that the supply of purines, as well as the purine synthesis of a cell can influence
BRD4 activity and thus play a role in the carcinogenesis process. Additionally, in cooperation with scientists from the University of Bari, Giulio's lab identified the protein responsible for the important transport of
NAD into mitochondria: the SLC25A51 transporter. Also his laboratory contributed to elucidate the role of
SLC38A9 in the mechanism by which the cell recognizes the presence of amino acids and thereby controls
mTOR activity.
Personalized medicine The central aim of
personalized medicine is to find the right treatment for the right patient at the right time. Giulio Superti-Furga developed new approaches with applications in precision medicine. In collaboration with the
Medical University of Vienna, Giulio developed a technique called "Pharmacoscopy" to screen primary patient material using automated
confocal microscopy and quantify single-cell events such as differential cell death, protein expression, cell morphology – creating robust and unique data sets. This technology allowed to determine the best treatment for patients with late stage and refractory hematological malignancies. Within the framework of EXALT (Extended Analysis for Leukemia/Lymphoma Treatment), this novel approach was tested and the result was that most advanced patients with aggressive hematological cancers clearly benefited from the approach.
Cancer and drug discovery Giulio Superti-Furga's research has a long-standing interest in understanding the molecular wiring of transformed cells of the
haematopoietic system, as well as studying the mode of action of targeted agents counteracting
leukemia cell proliferation. Giulio Superti-Furga's lab, in collaboration with the
Medical University of Vienna, identified sensitivities among 15
myeloid leukemia cell lines by using a small drug library (CeMM Library of Metabolic Drugs; CLIMET) targeting a variety of metabolic pathways. Previously, he also showed that SLC proteins located in different sub-cellular compartments are amenable to degradation by
ligand-induced proteolysis. Furthermore, in a pioneering study by his laboratory, they found that a particular transporter, was required for an experimental cancer drug to enter cells and exert its activity, which later led to a systematic investigation on the role of
transporters in determining the activity of a large and diverse set of
cytotoxic compounds. In 2018, driven by the interest in identifying underlying genetic determinants of drug response in a specific type of cancer of the
haematopoietic system, his lab reported on the mechanistic link between
RAS and the
LZTR1 gene, previously associated with a variety of rare disorders. Furthermore, Giulio's lab with Florian Grebien's lab and Johannes Zuber's lab were able to identify common, conserved molecular mechanisms that drive
oncogenesis in the context of the large number of different
MLL-fusion proteins. His laboratory has been also interested in better characterize the impact of known drugs on cells, using various
omics approaches. The laboratory developed a small molecule interaction mapping technology using mass
spectrometric thermal stability shifts at the proteome-wide level. Giulio also identified new target candidates for known drugs, previously unknown mechanisms of
drug resistance, "effector" genes for the compounds, mechanisms of synergy between compounds and, in a few cases, indeed new medical use of existing drugs.
Innate immunity, inflammation and infection Giulio Superti-Furga is also interested in understanding how the body responds to foreign threats, such as bacterial and viral infections, and how
autoimmune defenses are triggered when these defenses go awry. Recently, his lab determined by
biochemistry and mass spectrometry the molecular interactions that involved
SLC15A4, which led to the identification of an uncharacterized protein CXorf21 (named TASL). Strikingly, the lab found that TASL harbors a specific motif essential for the recruitment and activation of
IRF5. Over the past decade, his lab has discovered that
viruses employ a multitude of ways to both subvert as well as coup the host cellular system, and that the host largely relies on the
homeostasis of the cellular system to detect and inhibit viral intrusion. Furthermore, in collaboration with the
University of Geneva, discovered that
SLC4A7 plays an essential role in
phagocytosis and
phagosome acidification. His research also combined genetic perturbations of
sphingolipid metabolism with the quantification of diverse steps in
TLR signaling and mass spectrometry-based
lipidomics, which revealed that membrane lipid composition was affected by these perturbations. == Technology transfer and innovation ==