Wolfram Gruhn

Dr Wolfram Gruhn, Assistant Professor

After completing a PhD in molecular biology at the University of Heidelberg, I pursued my postdoctoral studies at the Gurdon Institute in Cambridge with Azim Surani. In 2023, I joined WMS as an Assistant Professor.

My research aims to understand the molecular mechanisms promoting human germline development. In particular, I am interested in the epigenetic remodeling in primordial germ cells and how this process can be affected by disease or environmental factors.

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Plain English

Sperm and egg possess the unique ability to initiate a new life cycle during fertilization. A newly formed embryo must activate genes in the right cells and at the right time to ensure normal development. Consequently, a fertilized egg inherits not only genetic information from the gametes but also crucial epigenetic instructions, enabling embryonic cells to regulate gene activity. In mammals, the complex process of establishing epigenetic information within gametes is initiated when primordial germ cells, the first precursors of gametes, appear in the early embryo. Disturbances in this process can result in infertility or abnormal embryo development. My research aims to understand the machinery guiding cells on their developmental path towards human gametes. In particular, I am interested in how epigenetic information is selected for inheritance through gametes to the next generation and whether this selection can be influenced by diseases or environmental factors.

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Dr Wolfram Gruhn, Assistant Professor

Email: Wolfram.Gruhn@warwick.ac.uk

Google Scholar | ORCID

Plain English

Technical Summary

The epigenome is a critical regulatory layer for DNA transcription, playing an essential role in defining the identity and developmental potential of cells. In mammals, cells of the early embryo are totipotent, signifying their ability to develop into any cell type formed in an individual's lifetime. A key foundation for totipotency and normal embryo development is laid in the embryonic germline, when primordial germ cells (PGCs) erase a substantial part of their epigenetic memory, in a process termed epigenetic resetting.

My research focuses on understanding the molecular mechanisms that govern the development of human PGCs and the intricate process of epigenetic resetting. Here, my lab aims to address: 1.) What transcription factor networks drive human PGC development? 2.) How do human PGCs decide which epigenetic information to erase or maintain? 3.) Can factors associated with the maternal environment or diseases impact human PGC development?

To address these questions, my lab uses human embryonic stem cell-based model systems to recapitulate early germline development in combination with various approaches for monitoring and manipulating transcription and protein-DNA interactions including RNA-seq, CUT&RUN, inducible degrons, and CRISPR.

Ultimately, the research in my lab aims to identify risk factors for infertility and abnormal development of the germline.

Selected publications:

Wolfram H Gruhn, Walfred W C Tang, Sabine Dietmann, João P Alves-Lopes, Christopher A. Penfold, Frederick C K Wong, Navin B Ramakrishna, M. Azim Surani, Epigenetic resetting in the human germline entails histone modification remodelling, (2023) Science Advances, DOI: 10.1126/sciadv.ade1257

João Pedro Alves-Lopes, Frederick C K Wong, Walfred W C Tang, Wolfram H Gruhn, Navin B Ramakrishna, Geraldine M Jowett, Kirsi Jahnukainen, M Azim Surani, Specification of human germ cell fate with enhanced progression capability supported by hindgut organoids, (2023) Cell Reports, DOI: 10.1016/j.celrep.2022.111907

Walfred W C Tang, Aracely Castillo-Venzor, Wolfram H Gruhn, Toshihiro Kobayashi, Christopher A Penfold, Michael D Morgan, Dawei Sun, Naoko Irie, M Azim Surani, Sequential enhancer state remodelling defines human germline competence and specification, (2022) Nature Cell Biology, DOI: 10.1038/s41556-022-00878-z

Julia Tischler, Wolfram H Gruhn, John Reid, Edward Allgeyer, Florian Buettner, Carsten Marr, Fabian Theis, Ben D Simons, Lorenz Wernisch, M Azim Surani, Metabolic regulation of pluripotency and germ cell fate through α‐ketoglutarate, (2019) EMBO Journal, DOI: 10.15252/embj.201899518

Seth W. Cheetham, Wolfram H Gruhn, Jelle van den Ameele, Robert Krautz, Tony D. Southall, Toshihiro Kobayashi, M. Azim Surani, Andrea H. Brand, (2018) Targeted DamID reveals differential binding of mammalian pluripotency factors, Development, DOI: 10.1242/dev.170209

Mathias S Gierl, Wolfram H Gruhn, Annika von Seggern, Nicole Maltry and Christof Niehrs, Gadd45g functions in male sex determination by promoting p38 signaling and Sry expression, (2012) Developmental Cell, DOI: 10.1016/j.devcel.2012.09.014