Cell Stress and Survival
A life without Cancer: tackling cellular homeostasis to discover novel diagnostic and therapeutical tools
Our research
The Cell Stress and Survival group (CSS) covers several research areas:
- Identifying novel factors regulating autophagy, mitophagy and pexophagy networks in cancer
- Investigating the regulation of cell migration, cell stem potential and cell division by autophagy and autophagy-related molecules in cancer cells
- Unveiling a role for autophagy in micronuclei homeostasis during oncogenesis
- Studying the specific regulation of centriolar satellites (doryphagy) and providing novel molecular targets to counteract cancer-associated centrosome abnormalities
- Combining the modulation of autophagy and stem cell potential in the treatment of childhood brain tumours
- Unravelling the molecular mechanisms at the basis of melanoma biology (in joint venture with the Melanoma Research Team directed by Senior Scientist Dr. Daniela De Zio).
CSS represents a virtuous balance between basic and translational science, and always expresses a fantastic mix of senior and junior scientists, committed in innovative cutting-edge research, open to national and international collaborations, and devoted to scientific excellence.
The group collaborates closely with the group Cellular Homeostasis and Recycling, led by Prof. Lisa Frankel, and the Redox Biology group, led by Prof. Giuseppe Filomeni. You can find us on X (@CecconiLabs).
Selected publications:
Maiani E, Milletti G, Nazio F, Holdgaard SG, Bartkova J, Rizza S, Cianfanelli V, Lorente M, Simoneschi D, Di Marco M, D'Acunzo P, Di Leo L, Rasmussen R, Montagna C, Raciti M, De Stefanis C, Gabicagogeascoa E, Rona G, Salvador N, Pupo E, Merchut-Maya JM, Daniel CJ, Carinci M, Cesarini V, O'sullivan A, Jeong YT, Bordi M, Russo F, Campello S, Gallo A, Filomeni G, Lanzetti L, Sears RC, Hamerlik P, Bartolazzi A, Hynds RE, Pearce DR, Swanton C, Pagano M, Velasco G, Papaleo E, De Zio D, Maya-Mendoza A, Locatelli F, Bartek J, Cecconi F: AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity. Nature 2021; April 14
Holdgaard SG, Cianfanelli V, Pupo E, Lambrughi M, Lubas M, Nielsen JC, Eibes S, Maiani E, Harder LM, Wesch N, Foged MM, Maeda K, Nazio F, de la Ballina LR, Dötsch V, Brech A, Frankel LB, Jäättelä M, Locatelli F, Barisic M, Andersen JS, Bekker-Jensen S, Lund AH, Rogov VV, Papaleo E, Lanzetti L, De Zio D, Cecconi F: Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites. Nat Commun 2019;10(1):4176
Di Rita A, Peschiaroli A, D Acunzo P, Strobbe D, Hu Z, Gruber J, Nygaard M, Lambrughi M, Melino G, Papaleo E, Dengjel J, El Alaoui S, Campanella M, Dötsch V, Rogov VV, Strappazzon F, Cecconi F.: HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα. Nat Commun 2018;9(1):3755
Cianfanelli V, Fuoco C, Lorente M, Salazar M, Quondamatteo F, Gherardini PF, De Zio D, Nazio F, Antonioli M, D'Orazio M, Skobo T, Bordi M, Rohde M, Dalla Valle L, Helmer-Citterich M, Gretzmeier C, Dengjel J, Fimia GM, Piacentini M, Di Bartolomeo S, Velasco G, Cecconi F: AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. Nat Cell Biol 2015;17(1):20-30
Nazio F, Strappazzon F, Antonioli M, Bielli P, Cianfanelli V, Bordi M, Gretzmeier C, Dengjel J, Piacentini M, Fimia GM, Cecconi F: mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat Cell Biol 2013;15(4):406-416
Fimia GM, Stoykova A, Romagnoli A, Giunta L, Di Bartolomeo S, Nardacci R, Corazzari M, Fuoco C, Ucar A, Schwartz P, Gruss P, Piacentini M, Chowdhury K, Cecconi F: Ambra1 regulates autophagy and development of the nervous system. Nature 2007;447(7148):1121-1125
Group leader: Francesco Cecconi
In 1998, Francesco Cecconi has made his initial groundbreaking discoveries on the molecular mechanisms of apoptosis, by identifying the developmental function of Apaf1, the protease activating factor 1.
Following long-term ambitious development of novel techniques, to study cell death and survival, and characterized by the use of highly interdisciplinary approaches, his own group was established in Rome, Italy, in 2000. Since 2006 Francesco Cecconi is Full Professor at the University of Rome Tor Vergata, where he teaches Developmental Biology.
Later, after his seminal work on the activating molecule in Beclin 1-regulated autophagy (AMBRA1), Prof. Cecconi became a world-leader scientist in the field of autophagy in development and disease, placing his group among the most prominent European teams in the fundamental research about the key cellular process of autophagy. In particular, he discovered AMBRA1 as being one of the few members of the vertebrate autophagy core complex and of the mitophagy apparatus, a downstream direct target of mTORC1, responsible of autophagosome formation, essential for brain development and immune cell homeostasis, and involved in controlling cell proliferation, death and differentiation.
Francesco Cecconi directs since 2013 in Copenhagen Cell Stress and Survival at DCRC, through which he is committed in elucidating the role of autophagy in a number of tumors and in identifying novel strategies in cancer treatment, based on autophagy manipulation. His work is best characterized as a successful combination of uncompromised and innovative basic science at highest quality with strong translational interest.
Of note, Prof. Cecconi has published more than 200 papers in important scientific journals, such as Cell, Nature, Nature Cell Biology, Nature Neuroscience, which obtained >23,000 citations by peers; further, he is elected member of the European Molecular Biology Organization (EMBO), the European Cell Death Organization (ECDO), the Cell Death Society (CDS) and the Nordic Autophagy Society (NAS). Also, Francesco Cecconi is Deputy Director of the Center of Excellence for Autophagy, Recycling and Disease (CARD) in Copenhagen.
He has acted as mentor of 23 Postdocs, 26 PhD, and 100+ Master Students and, since 2013, he has Co-supervised students enrolled in the PhD School in Molecular Mechanisms of Disease (MoMed) of the University of Copenhagen.Last, in the period 2017-2019 he has been the Coordinator of the PhD School in Molecular Cell Biology at the University of Rome Tor Vergata.
ORCID: 0000-0002-5614-4359
Key funding
Novo Nordisk Foundation
Danish Cancer Society Scientific Committee
Bjarne Saxhof Foundation
Melanoma Research Team
The Melanoma Research Team is translational research oriented and applies cell and molecular biology-based techniques alongside preclinical models to discover new therapeutic treatments for melanoma.
Our research mainly focuses on the biological mechanisms of melanoma development and immune responses to explore novel treatment strategies in preclinical models of melanoma.
Melanoma is the deadliest skin cancer and is extremely difficult to treat when it recurs. Although melanoma is curable in the early stages, metastatic melanoma continues to be a therapeutic challenge due to the development of therapy resistance. However, a remarkable improvement in the survival of patients with advanced melanoma has been achieved by the clinical employment of i) kinase inhibitors in BRAF/RAS-mutated patients (Targeted Therapy) and ii) immune-checkpoint inhibitors (Immune Therapy).
We aim to unravel the molecular mechanisms underlying melanoma development and resistance to therapy - both targeted and immune-based therapies - by using genetically modified mouse models (GEMM) and GEMM-derived allografts (GDA) that mimic the disease's natural progression, and artificial skin models.
One of our main goals is to understand the mechanisms behind melanoma heterogeneity and plasticity, as well as the interplay of cancer cells with the tumor microenvironment. In particular, we aim to discover new molecular players of phenotype switching in melanoma and identify new drug candidates to apply for melanoma therapy.
In addition, we seek to find new therapeutic strategies in combination with immunotherapy, focusing on increasing the efficacy of immune checkpoint inhibitors. We are also interested in understanding how the combination of host-intrinsic and -extrinsic factors impacts tumor immunity and immunotherapy response.
We closely collaborate with the Rigshospitalet (Department of Oncology and Pediatrics) and Herlev Hospital (Center for Cancer Immune Therapy) in Copenhagen, as well as with the University of Southern Denmark (Department of Molecular Medicine and Biochemistry & Molecular Biology) in Odense.
Find us at Twitter (DeZio_Lab @melanomateam)
Di Leo L, Pagliuca C, Kishk A, Rizza S, Tsiavou C, Pecorari C, Dahl C, Pacheco MP, Tholstrup R, Brewer JR, Berico P, Hernando E, Cecconi F, Ballotti R, Bertolotto C, Filomeni G, Gjerstorff MF, Sauter T, Lovat P, Guldberg P, De Zio D. AMBRA1 levels predict resistance to MAPK inhibitors in melanoma. Proc Natl Acad Sci U S A. 2024 Jun 18;121(25):e2400566121.
Frias A, Di Leo L, Antoranz A, Nazerai L, Carretta M, Bodemeyer V, Pagliuca C, Dahl C, Claps G, Mandelli GE, Andhari MD, Pacheco MP, Sauter T, Robert C, Guldberg P, Madsen DH, Cecconi F, Bosisio FM, De Zio D. Ambra1 modulates the tumor immune microenvironment and response to PD-1 blockade in melanoma. J Immunother Cancer. 2023 Mar;11(3):e006389
Nazerai L, Willis SC, Yankilevich P, Di Leo L, Bosisio FM, Frias A, Bertolotto C, Nersting J, Thastrup M, Buus S, Thomsen AR, Nielsen M, Rohrberg KS, Schmiegelow K, De Zio D: Thiopurine 6TG treatment increases tumor immunogenicity and response to immune checkpoint blockade. Oncoimmunology 2023;12:2158610
Di Leo L, Bodemeyer V, Bosiso FM, Claps G, Carretta M, Rizza S, Faienza F, Frias A, Khan S, Bordi M, Pacheco MP, Di Martino J, Bravo-Cordero JJ, Daniel CJ, Sears RC, Donia M, Madsen DH, Guldberg P, Filomeni G, Sauter T, Robert C, De Zio D*, Cecconi F*: Loss of Ambra1 promotes melanoma growth and invasion. Nat Commun 2021; May 5. * Co-last authors
Maiani E, Milletti G, Nazio F, Holdgaard SG, Bartkova J, Rizza S, Cianfanelli V, Lorente M, Simoneschi D, Di Marco M, D'Acunzo P, Di Leo L, Rasmussen R, Montagna C, Raciti M, De Stefanis C, Gabicagogeascoa E, Rona G, Salvador N, Pupo E, Merchut-Maya JM, Daniel CJ, Carinci M, Cesarini V, O'sullivan A, Jeong YT, Bordi M, Russo F, Campello S, Gallo A, Filomeni G, Lanzetti L, Sears RC, Hamerlik P, Bartolazzi A, Hynds RE, Pearce DR, Swanton C, Pagano M, Velasco G, Papaleo E, De Zio D, Maya-Mendoza A, Locatelli F, Bartek J, Cecconi F: AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity. Nature 2021; April 14
Team leader: Daniela De Zio
Daniela De Zio is the head of the Melanoma Research Team. She has a strong background in cell and molecular biology, and mouse genetics and manipulation. She received her PhD in 2006 from the University of Rome-Tor Vergata and carried out post-doctoral research in different institutes in Italy and Denmark.
She has started a new line of research in the Cell Stress and Survival group (CSS) at the Danish Cancer Institute aimed at finding novel prognostic markers and therapeutic targets for melanoma by means of preclinical models.
She has been one of the few European grantees of the prestigious Young Investigator Award from the American foundation Melanoma Research Alliance.
She has been member of the Cluster for Cancer and Infectious Disease at the Department of Drug Design and Pharmacology, University of Copenhagen. She is currently Associate Professor in basal and translational cancer research at the Department of Molecular Medicine, Unit of Cancer and Inflammation Research, University of Southern Denmark (SDU).
ORCID: 0000-0002-9454-402X
MEL Staff
MEL Key funding
The Melanoma Research Team is among others funded by:
Danish Cancer Society (KBVU)
LEO foundation
NEYE fonden
Kai Lange og Gunhild Kai Langes Fond
Melanoma Research Alliance