CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences: Giulio Superti-Furga Group

Research Focus

Key for any living entity, such as a human cell, is the ability to contain an own environment within membranes that not only preserves the genetic material, but also allows chemical reactions to be efficient and generate energy. Management of the interface between the external world and the biochemical self occurs through the activity and regulation of membrane transporters. The Superti-Furga laboratory considers transporters ideal means to tune cell metabolism while representing a manifestation of a cell’s appetite for nutrients, integrated over the environment’s offer.

The GSF Lab science summarized in five points:

We investigate the mechanisms and logic of how the concentration of individual metabolites, ions, and nutrients is achieved, coordinated, and maintained within cells.
We study the roles that varying concentrations of small molecules in the intracellular and extracellular environments play in defining cellular identity, maintaining homeostasis, and influencing disease processes.
We perturb specific metabolic processes and signaling pathways to alter cell growth and analyze their interdependence.
We maintain a strategic focus on membrane transporters as druggable regulators of metabolism, and on proteostasis as a therapeutic link between growth and metabolic control.
We actively promote translational research through the design and discovery of small molecule drugs that modulate cellular homeostasis, and through ex vivo assessment of drug action in cancer and inflammatory diseases.

Metabolism and regulation of metabolite concentration

All cells are surrounded by a lipid bilayer forming a selective barrier between the aqueous cell interior and the external environment. Yet, cells must import nutrients, water, and ions to sustain cellular metabolism, generate energy, and produce the building blocks for genome preservation and replication. While few molecules can diffuse through the membrane, most—including vitamins, hormones, xenobiotics, phytochemicals, pesticides, microbiome-derived metabolites, and critically, pharmaceutical drugs—require membrane transporters for cellular entry.

These transporters are the gatekeepers at the chemistry-biology interface and mediate interactions between organisms and their environments. As one of the largest and underexplored gene families in humans, we proposed intensifying research on the SLC (solute carrier) transporter superfamily—the most extensive group of human membrane transporters (César-Razquin, Snijder et al, Cell 2015).

Our lab investigates how SLC transporters regulate metabolic flux, drug transport, and cellular signaling. A deeper understanding of the specificity and function of individual SLCs and their networks could improve drug targeting and provide insights into how biological systems are shaped by their chemical environments.

Cancer targets and drug discovery

Most effective therapeutic agents act not through single targets, but by inducing broad and intricate perturbations of biological systems. By applying a rigorous, systems biology approach to chemical compound characterization, we aim to improve our understanding of drug action, facilitate patient stratification, and enhance the precision of clinical trials. This approach may also aid in reducing side effects and guide combination therapy strategies with existing treatments.

The GSF lab has a long-standing interest in hematopoietic malignancies, particularly the molecular mechanisms of leukemia. From BCR-ABL signaling in Chronic Myeloid Leukemia (CML) to various forms of Acute Myeloid Leukemia (AML), we utilize state-of-the-art methods to explore drug resistance and uncover novel therapeutic targets in targeted cancer therapy.

Innate immunity, inflammation, and infection

Understanding how the human body detects and responds to pathogens such as viruses and bacteria, and how autoimmune responses are activated or dysregulated, is essential for developing new treatments across diverse inflammatory and infectious diseases.

Over the past decade, we have:

Discovered a novel adaptor protein linking innate and adaptive immunity.
Revealed roles of SLC transporters in viral infection survival and bacterial phagocytosis.
Demonstrated how membrane lipid composition influences innate immune signaling.
Explored how modulating programmed cell death can be harnessed to mitigate inflammation.

Biosketch

Giulio Superti-Furga, Ph.D., is Scientific Director and CEO of the Research Center of Molecular Medicine of the Austrian Academy of Sciences and Professor of Medical Systems Biology at the Center for Physiology Medical University of Vienna. He is also Scientific Director of the Ri.MED Foundation in Palermo, Italy and the designated Director General of the new research center of the foundation. Since 2024 he is chair of EU-LIFE , the alliance of fifteen leading life science institutes in Europe.

For three years, (2017-2019) he has been a member of the Scientific Council of the ERC (European Research Council).

He performed his undergraduate and graduate studies in molecular biology at the University of Zurich, Switzerland, at Genentech Inc., South San Francisco, USA, and at the Institute for Molecular Pathology in Vienna (I.M.P.), Austria. He was a post-doctoral fellow and Team Leader at the European Molecular Biology Laboratory (EMBL) until 2004. For several years he served as professor of Biotechnology at the University of Bologna. In 2000, he co-founded the biotech company Cellzome Inc., where for five years he was Scientific Director and responsible for the Heidelberg research site. He also co-founded the biotech companies Haplogen, Allcyte, Proxygen and Solgate.

His most significant scientific contributions are the elucidation of basic regulatory mechanisms of tyrosine kinases in human cancers, discovery of fundamental organization principles of the proteome of higher organisms and the discovery of a number of key proteins in innate immunity. Since more than ten years, he has been leading international efforts to understand the function of the human transportome, the ensemble of membrane transporters.

At CeMM, he promoted a unique mode of super-cooperation, connecting biology with medicine, experiments with computation, discovery with translation, and science with society and the arts.

Giulio Superti-Furga is a member of five science academies, including the Austrian Academy of Sciences and the the German Academy of Sciences Leopoldina.

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Check here Giulio Superti-Furga’s genome: PGA-1

Selected Papers

Orcid ID: 0000-0002-0570-1768 (link)
Researcher ID: F-4755-2015 (link)
Google scholar

Dvorak V, Casiraghi A, Colas C, Koren A, Tomek T, Offensperger F, Rukavina A, Tin G, Hahn E, Dobner S, Frommelt F, Boeszoermenyi A, Bernada V, Hannich JT, Ecker GF, Winter GE, Kubicek S, Superti-Furga G. Paralog-dependent isogenic cell assay cascade generates highly selective SLC16A3 inhibitors. Cell Chem Biol. 2023 Aug 17;30(8):953-964.e9. (abstract)

Kornauth C, Pemovska T, Vladimer GI, et al. Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematological Cancers and Identifies Exceptional Responders. Cancer Discov. 2022 Feb;12(2):372-387. (abstract)

Pemovska T et al. Metabolic drug survey highlights cancer cell dependencies and vulnerabilities. Nat Commun. 2021 Dec 14;12(1):7190. (abstract)

Li et al. Cell-surface SLC nucleoside transporters and purine levels modulate BRD4-dependent chromatin states. Nat Metab. 2021 May;3(5):651-664. (abstract)

Girardi et al. Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import. Nat Commun. 2020 Dec 1;11(1):6145. (abstract)

Meixner E et al. A substrate-based ontology for human solute carriers. Mol Sys Biol. 2020 Jul;16(7):e9652. (abstract)

Bensimon A et al. Targeted Degradation of SLC Transporters Reveals Amenability of Multi-Pass Transmembrane Proteins to Ligand-Induced Proteolysis. Cell Chem Biol. 2020 Jun 18;27(6):728-739.e9. (abstract)

Heinz et al. TASL is the SLC15A4-associated adaptor for IRF5activation by TLR7-9. Nature. 2020 May;581(7808):316-322. (abstract)

Girardi E et al. A widespread role for SLC transmembrane transporters in resistance to cytotoxic drugs. Nat Chem Biol. 2020 Apr 16(4) 469-478. (abstract)

Fauster A et al. Systematic genetic mapping of necroptosis identifies SLC39A7 as modulator of death receptor trafficking. Cell Death Differ. 2019 Jun; 26(6) 1138-1155. (abstract)

Bigenzahn JW, et al. LZTR1 is a regulator of RAS ubiquitination and signaling. Science. 2018 Dec 7;362(6419):1171-1177. (abstract)

Vladimer GI*, Snijder B*, et al. Global survey of the immunomodulatory potential of common drugs. Nat Chem Biol. 2017;13(6):681-690. (abstract)

César-Razquin A, et al. A Call for Systematic Research on Solute Carriers. Cell. 2015 Jul 30;162(3):478-87. (abstract)

Rebsamen M, et al. SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature. 2015 Mar 26;519(7544):477-81. (abstract)

Köberlin MS, et al. A conserved circular network of coregulated lipids modulates innate immune responses. Cell. 2015;162(1):170-83. (abstract)

Huber KV, et al. Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature. 2014 Apr 10;508(7495):222-7. (abstract)

Winter GE, et al. The solute carrier SLC35F2 enables YM155-mediated DNA damage toxicity. Nate Chem Biol. 2014 Sep;10(9):768-73. (abstract)

Pichlmair A, et al. Viral immune modulators perturb the human molecular network by common and unique strategies. Nature. 2012 Jul 26;487(7408):486-90. (abstract)

Winter GE, et al. Systems-pharmacology dissection of a drug synergy in imatinib-resistant CML. Nat Chem Biol. 2012 Nov;8(11):905-12. (abstract)

Grebien F, et al. Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis. Cell. 2011 Oct 14;147(2):306-19. (abstract)

Pichlmair A, et al. IFIT1 is an antiviral protein that recognizes 5'-triphosphate RNA. Nat Immunol. 2011 Jun 5;12(7):624-30. (abstract)

Bürckstümmer T, et al. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol. 2009 Mar;10(3):266-72. (abstract)

Gavin AC, et al. Proteome survey reveals modularity of the yeast cell machinery. Nature. 2006 Mar 30;440(7084):631-6. (abstract)

Bouwmeester T, et al. A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat Cell Biol. 2004 Feb;6(2):97-105. (abstract)

Hantschel O, et al. A myristoyl/phosphotyrosine switch regulates c-Abl. Cell. 2003 Mar 21;112(6):845-57. (abstract)

Gavin AC, et al. Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature. 2002 Jan 10;415(6868):141-7. (abstract)