Sebastian Gregoricchio
Verified @gmail.com
Scopus Publications
- Regulatory grammar in human promoters uncovered by MPRA-based deep learning
Lucía Barbadilla-Martínez, Noud Klaassen, Vinícius H. Franceschini-Santos, Jérémie Breda, Hatice Yücel, et al.
Nature, 2026 - DEprot: a comprehensive R-package for the analysis of label-free quantitation mass spectrometry data
Nils Eickhoff, Liesbeth Hoekman, Onno Bleijerveld, Andries M Bergman, Wilbert Zwart, et al.
Nar Genomics and Bioinformatics, 2026
In recent years, studies investigating protein–protein interactions on a proteome-wide scale have increased exponentially. These developments were achieved through implementation of new techniques, as well as improvements in mass spectrometry hardware. However, issues specific to this type of technique, such as distinct imputation of random and not-at-random missing proteins, have not been completely addressed. Here, we present DEprot, an R-package providing a comprehensive toolset for end-to-end analysis and visualization of proteomics data. Moreover, we implemented a serial imputation strategy for handling non-random missing values, particularly suitable for protein enrichment techniques and knockout conditions. - Fasting boosts breast cancer therapy efficacy via glucocorticoid activation
Nuno Padrão, Tesa M. Severson, Sebastian Gregoricchio, Ana Guijarro, Catrin Lutz, et al.
Nature, 2026 - TRIM33 loss reduces androgen receptor transcriptional output and H2BK120 ubiquitination
Nils Eickhoff, Janina Janetzko, Nuno Padrão, Sebastian Gregoricchio, Joseph C. Siefert, et al.
Communications Biology, 2025 - Endometrial tumorigenesis involves epigenetic plasticity demarcating non-coding somatic mutations and 3D-genome alterations
Sebastian Gregoricchio, Aleksandar Kojic, Marlous Hoogstraat, Karianne Schuurman, Suzan Stelloo, et al.
Genome Biology, 2025 - Germline–Somatic Liaison Dictates Cancer Subtypes via de novo Steroid Biosynthesis
Paola Gasperini, Alessandro Alaimo, Blerta Stringa, Yoon-Mi Chung, Yari Ciani, et al.
Cancer Discovery, 2025
The biological mechanisms underlying the cooperation between germline genetic variants and somatic mutations during carcinogenesis are rarely elucidated. In this study, characterizing isogenic prostate cancer cell lines, we dissected the interplay between a germline variant at the 7p14.3 locus (rs1376350, G>A) and early recurrent prostate cancer–specific mutation in the speckle-type POZ protein (SPOP) gene across human prostate adenocarcinomas. The transcriptomes of multiple edited models pointed to GLI3 and the Hedgehog signaling pathway in a genotype-specific manner, whereas SPOP mutation and androgen receptor stimulation promote GLI3 accumulation in the full-length, transcriptionally active form. This, in turn, triggers the cell-autonomous production of steroids that prostate cancer relies on, in line with the enhanced responsiveness of SPOP-mutated prostate cancer to androgen deprivation therapy. These data demonstrate that germline variants dictate prostate cancer somatic evolution and suggest opportunities to jointly model germline–somatic relationship to help untangle the complexity of human cancer. Significance: Significant heritability is observed for common cancer types worldwide. The molecular mechanisms by which inherited genetics facilitate cancer initiation might transit through its cooperation with specific somatic events that then dictate the tumor features. Through a germline–somatic tandem leading to steroid biosynthesis, we suggest a paradigm to study cancer initiation. - A 3D genome compendium of breast cancer progression
Teun van den Brand, Maria Donaldson Collier, Koen D. Flach, Sebastian Gregoricchio, Isabel Mayayo-Peralta, et al.
Iscience, 2025 - Tamoxifen induces PI3K activation in uterine cancer
Kirsten Kübler, Agostina Nardone, Shankara Anand, Daniel Gurevich, Jianjiong Gao, et al.
Nature Genetics, 2025
Mutagenic processes and clonal selection contribute to the development of therapy-associated secondary neoplasms, a known complication of cancer treatment. The association between tamoxifen therapy and secondary uterine cancers is uncommon but well established; however, the genetic mechanisms underlying tamoxifen-driven tumorigenesis remain unclear. We find that oncogenic PIK3CA mutations, common in spontaneously arising estrogen-associated de novo uterine cancer, are significantly less frequent in tamoxifen-associated tumors. In vivo, tamoxifen-induced estrogen receptor stimulation activates phosphoinositide 3-kinase (PI3K) signaling in normal mouse uterine tissue, potentially eliminating the selective benefit of PI3K-activating mutations in tamoxifen-associated uterine cancer. Together, we present a unique pathway of therapy-associated carcinogenesis in which tamoxifen-induced activation of the PI3K pathway acts as a non-genetic driver event, contributing to the multistep model of uterine carcinogenesis. While this PI3K mechanism is specific to tamoxifen-associated uterine cancer, the concept of treatment-induced signaling events may have broader applicability to other routes of tumorigenesis. - TRIM24 as a therapeutic target in endocrine treatment–resistant breast cancer
Nuno Padrão, Sebastian Gregoricchio, Nils Eickhoff, Jing Dong, Lara Luzietti, et al.
Proceedings of the National Academy of Sciences of the United States of America, 2025
While Estrogen receptor alpha (ERα)+ breast cancer treatment is considered effective, resistance to endocrine therapy is common. Since ERα is still the main driver in most therapy-resistant tumors, alternative therapeutic strategies are needed to disrupt ERα transcriptional activity. In this work, we position TRIM24 as a therapeutic target in endocrine resistance, given its role as a key component of the ERα transcriptional complex. TRIM24 interacts with ERα and other well-known ERα cofactors to facilitate ERα chromatin interactions and allows for maintenance of active histone marks including H3K23ac and H3K27ac. Consequently, genetic perturbation of TRIM24 abrogates ERα-driven transcriptional programs and reduces tumor cell proliferation capacity. Using a recently developed degrader targeting TRIM24, ERα-driven transcriptional output and growth were blocked, effectively treating not only endocrine-responsive cell lines but also drug-resistant derivatives thereof as well as cell line models bearing activating ESR1 point mutations. Finally, using human tumor-derived organoid models, we could show the efficacy of TRIM24 degrader in the endocrine-responsive and -resistant setting. Overall, our study positions TRIM24 as a central component for the integrity and activity of the ERα transcriptional complex, with degradation-mediated perturbation of TRIM24 as a promising therapeutic avenue in the treatment of primary and endocrine resistance breast cancer. - Epigenetic profiling identifies markers of endocrine resistance and therapeutic options for metastatic castration-resistant prostate cancer
Tesa M. Severson, Emma Minnee, Yanyun Zhu, Karianne Schuurman, Holly M. Nguyen, et al.
Cell Reports Medicine, 2025 - Zincore, an atypical coregulator, binds zinc finger transcription factors to control gene expression
Daniëlle Bianchi, Razvan Borza, Erica De Zan, Guizela Huelsz-Prince, Sebastian Gregoricchio, et al.
Science, 2025 - Comprehensive functional annotation of ESR1-driven enhancers in breast cancer reveals hierarchical activity independent of genomic and epigenomic contexts
Yanis Zekri, Sebastian Gregoricchio, Elif Yapıcı, Chia-Chi Flora Huang, Tunç Morova, et al.
Genome Research, 2025 - Targeting DOT1L and EZH2 synergizes in breaking the germinal center identity of diffuse large B-cell lymphoma
Camiel Göbel, Rachele Niccolai, Marnix Hugo Philip de Groot, Jayashree Jayachandran, Joleen Traets, et al.
Blood, 2025 - Chromatin context-dependent effects of epigenetic drugs on CRISPR-Cas9 editing
Ruben Schep, Max Trauernicht, Xabier Vergara, Anoek Friskes, Ben Morris, et al.
Nucleic Acids Research, 2024 - Estrogen receptor 1 chromatin profiling in human breast tumors reveals high inter-patient heterogeneity with enrichment of risk SNPs and enhancer activity at most-conserved regions
Stacey E.P. Joosten, Sebastian Gregoricchio, Suzan Stelloo, Elif Yapıcı, Chia-Chi Flora Huang, et al.
Genome Research, 2024 - PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription
Isabel Mayayo-Peralta, Sebastian Gregoricchio, Karianne Schuurman, Selçuk Yavuz, Anniek Zaalberg, et al.
Nucleic Acids Research, 2023 - FANCA deficiency promotes leukaemic progression by allowing the emergence of cells carrying oncogenic driver mutations
Patrycja Pawlikowska, Laure Delestré, Sebastian Gregoricchio, Alessia Oppezzo, Michela Esposito, et al.
Oncogene, 2023 - SnHiC: A complete and simplified snakemake pipeline for grouped Hi-C data analysis
Sebastian Gregoricchio, Wilbert Zwart
Bioinformatics Advances, 2023 - HDAC1 and PRC2 mediate combinatorial control in SPI1/PU.1-dependent gene repression in murine erythroleukaemia
Sebastian Gregoricchio, Lélia Polit, Michela Esposito, Jérémy Berthelet, Laure Delestré, et al.
Nucleic Acids Research, 2022 - CHIPIN: ChIP-seq inter-sample normalization based on signal invariance across transcriptionally constant genes
Lélia Polit, Gwenneg Kerdivel, Sebastian Gregoricchio, Michela Esposito, Christel Guillouf, et al.
BMC Bioinformatics, 2021
