Scientific topics
Keywords
ITMO
Theo Hirsch Researcher, cancer genomics and bioinformatics
Course and current status
Permanent Researcher (CRCN Inserm) - Liver cancer evolution and response to therapy
Spatio-temporal evolution of liver cancers in interaction with the environment
INSERM U1138 - Cordeliers Research Center - Paris, France | Lab. head Pr J Zucman-Rossi
2023 - Present
Post-doctoral Researcher - Cancer genomics and bioinformatics
Tumor heterogeneity and microenvironment in pediatric and adult liver tumors
INSERM U1138 - Cordeliers Research Center - Paris, France | Lab. head Pr J Zucman-Rossi
2017 - 2023
PhD student in Cell biology
Cell signalling pathways coupled to the prion protein: from physiology to pathology
INSERM U1124 - Université Paris Descartes | Director: Dr Sophie Mouillet-Richard
2012 - 2016
Masters student
microRNAs involved in the differentiation of neural stem cells towards functional neurons
INSERM U747 - Université Paris Descartes | Lab. head Pr O Kellermann
2011 - 2012 | 2 internships (3 months then 9 months)
Education
- 2012-2016 PhD in Cell Biology, Paris Descartes University, France
- 2011-2012 Master's Degree in Cell Biology and Development, Paris Descartes University, France
- 2008-2012 École Polytechnique, Palaiseau, France
Multidisciplinary scientific training with a focus on biology - 2006-2008 Classe préparatoires aux grandes écoles, Louis-le-Grand, Paris, France
Undergraduate courses to prepare nationwide competitive exams in sciences
Scientific summary
Current topics
- Genomics of pediatric and adult liver cancers
- Tumor plasticity and evolution
- Immune microenvironment of the tumor
- Overcoming cisplatin resistance in hepatoblastoma
- Single cell and spatial transcriptomics
- High-plex immunoflorescence
Research interests
My research is focused on tumor heterogeneity and microenvironment in pediatric and adult liver cancers. It is based on integrated genomic analyses performed on retrospective cohorts with good clinical annotation, allowing to associate molecular features with biological, histological or clinical characteristics along the evolution of tumors.
In adult liver cancer, integrating RNAseq and whole genome / exome sequencing on a cohort of 150 hepatocellular carcinomas (HCC), we showed that HCC with a biallelic inactivation of the BAP1 gene form a homogeneous group of tumors. We discovered how copy-number alterations specific of these HCC activate the PKA pathway, explaining the similarities between BAP1 HCC and the rare tumors fibrolamellar carcinomas, that activate PKA through the DNAJB1-PRKACA driver fusion.
See the publication in Journal of Hepatology and a Twitter thread explaining the results.
In pediatric liver cancer, our integrated genomic analysis showed the high plasticity of hepatoblastoma cells, that are able to switch between 3 phenotypes coexisting within the same tumor. By analyzing the mutational signature created by cisplatin adducts on DNA, we were able to follow which cells are able to proliferate despite chemotherapy, and discovered that the so-called 'Liver Progenitor' cells are resistant to cisplatin and are at the origin of tumor progression and relapse / metastasis. We were thus able to screen for new drugs specifically targeting this 'Liver Progenitor' phenotype in order to bypass cisplatin resistance.
See the publication in Cancer Discovery, a comment in Nature Reviews, the press release (in French) and a Twitter thread explaining the results.
Currently, I try to take advantage of two innovative technologies, single-nucleus RNAseq and spatial transcriptomics, to get a multi-level comprehension of the interactions between immune and tumor cells along the evolution of tumors in space and time.
Links
- Pubmed: Hirsch TZ
- ORCID: 0000-0003-4428-2997
- Google Scholar: WrKA3eEAAAAJ
- Twitter: @TZ_Hirsch
- FunGeST team: http://zucmanlab.com/
- Cordelier Research Center: www.crcordeliers.fr
