Davide Seruggia Group

Davide Seruggia Group

Davide Seruggia © Email: davide.seruggia(at)ccri.at

Pediatric Leukemia Biology

We focus of non-coding regulatory elements, chromatin modifiers and other epigenetic factors to understand how pediatric leukemia develops and to find new targets of therapy.

Our Research

The dark side of the genome

Functional non-coding regions such as enhancers and insulators play an essential role in disease, and mutations at non-coding elements can drive observable phenotypic changes comparable to those driven by mutations at coding sequences (see Seruggia et al. 2015Seruggia et al. 2020). Sequence variation at intergenic regions is associated with risk of pediatric B-ALL. However, due to lack of appropriate technology, just a limited number of disease-related regulatory sequences have been described, leaving many potential targets of therapy to be discovered. For these reasons, our goal is to investigate the contribution of non-coding sequences in cancer. We focus on development of leukemia and drug resistance. What is the role of enhancers in the acquisition of drug resistance? How chromatin topology affects gene expression in leukemia? What is the effect of sequence variation at enhancers whose mutation is associated with leukemia? We use epi/genome editing (CRISPR, CRISPRi, CRISPRa), chromatin profiling (ChIP-seq, Cut and Run, ATAC-seq) and computational biology to answer these questions.

Targeting chromatin modifiers in pediatric malignancies

We previously reported a connection between two chromatin modifiers of the SAGA complex and self-renewal in mouse embryonic stem cells (see Seruggia et al 2019)We discovered that loss of TAF5L and TAF6L in mouse embryonic stem cells results in a dramatic reduction in H3K9ac, followed by downregulation of MYC along with its target genes. Since gene expression programs between stem cells and cancer cells are highly similar, we hypothetize that components of the SAGA complex are essential in MYC-driven malignancies. Can we harness vulnerabilities within the SAGA members to treat MYC-driven malignancies? What is the role of SAGA components in normal hematopoiesis and in leukemia? We use mouse modelsgenomics and genome editing to answer these questions.

Funding

Horizon 2020 Excellent Science Call European Research Council (ERC)-2020-STG (Starting Grant) Find-seq: functional interrogation of non-coding DNA sequences in leukemia development and drug resistance.

Collaborators

  • Luca Pinello, PhD (Massachusetts General Hospital and Harvard Medical School)
  • Daniel Bauer, MD PhD (Boston Children’s Hospital and Harvard Medical School)

Selected Articles

Full list of publications here

About Davide Seruggia

Davide Seruggia obtained a degree in Biotechnology at the University of Milano-Bicocca (Italy) in 2010, and a PhD in Molecular Biology at the National Centre for Biotechnology (CNB-CSIC) in Madrid (Spain) in 2014. During his PhD under the supervision of Lluis Montoliu, he focused on non-coding DNA regulatory sequences and generated several mouse lines carrying deletions of selected enhancers. Analysis of these mice highlighted the relevance of non-coding elements in regulating patterns of gene expression. In 2015 he joined the laboratory of Stuart H. Orkin at Boston Children’s Hospital and Harvard, where he trained in hematology, stem cell biology and genomics. In Boston, Davide used genomics and genome editing to explore the role of epigenetic factors, chromatin modifiers and transcriptional co-activators in the context of mouse embryonic stem cells, and generated a series of mouse models to study how chromatin modifiers control hematopoiesis, erythropoiesis and the expression of globin genes. In 2019, he was promoted to Instructor in Pediatrics at Harvard Medical School and attracted funding from the WES Foundation and Pedals for Pediatrics to investigate non-coding sequence variation in pediatric leukemia. In 2021 Davide joined the St. Anna Children’s Cancer Research Institute as Principal Investigator and CeMM as Adjunct Principal Investigator, supported by an ERC Starting Grant.

Team Pediatric Leukemia Biology

Dr. Davide Seruggia (PhD)

Dr. Davide Seruggia (PhD)

Principal Investigator

davide.seruggia(at)ccri.at +43 1 40470 4030
Leonie Lehmayer, MSc

Leonie Lehmayer, MSc

PhD Student

leonie.lehmayer(at)ccri.at
Anzhelika Karjalainen (MSc)

Anzhelika Karjalainen (MSc)

Lab Manager / TA

anzhelika.karjalainen(at)ccri.at +43 1 40470 4022
Ana Patricia Kutschat (PhD)

Ana Patricia Kutschat (PhD)

Postdoctoral Fellow

ana.kutschat(at)ccri.at +43 1 40470 0
Maciej Piotr Zaczek, PhD

Maciej Piotr Zaczek, PhD

Postdoctoral Fellow

maciej.zaczek(a)ccri.at