Professor Ben Simons

Professor Ben Simons

Tracing stem cell fate in development, maintenance and disease

Email: bds10@cam.ac.uk     |     Departmental Affiliation: Applied Mathematics and Theoretical Physics　

Laboratory: Gurdon Institute

Research

Plain English: In adults, many tissues such as epidermis, blood, and gut undergo routine and constant turnover. The maintenance and repair of such tissues relies upon stem cells. As with embryonic stem cells, tissue stem cells are defined by their capacity to self-renew and to differentiate into the more specialised cell types. However, in contrast to embryonic stem cells, tissue stem cells must achieve a perfect balance between proliferation and differentiation. Resolving the mechanisms of balance represent one of the defining questions of stem cell biology. To address this question, most studies focus on the identification of molecular regulatory factors. However, such factors are rare and often unspecific. By exploiting methods of population dynamics and statistical physics, the Simons Group have shown that, in homeostasis, stem cells must follow simple and restricted patterns of fate, which impart characteristic signatures in the size distribution of surviving clones. They are using this general methodology to explore the pattern of tissue maintenance in normal adult tissues, and to address the mechanisms of dysregulation in disease, cancer and aging.

Research Focus: Research in the Simons Group combines experimental lineage tracing strategies and single-cell methods with concepts from non-equilibrium statistical physics and mathematics to address the fate behaviour of stem and progenitor cells in the development, maintenance and regeneration of tissues, and factors leading to their dysregulation in diseased states.

In particular, they have resolved strategies of stem cell self-renewal in the maintenance of epithelial tissues, including mammalian brain, epidermis, intestine, lung and testis. Their studies have emphasized the role of stochastic renewal programmes in the regulation of stem cell fate, questioning the nature of stem cell identity and function. They have extended these approaches to study the development and patterning of adult tissues, including the eye, heart, mammary epithelium, pancreas and skin epidermis. At the same, they are collaborating with partner labs to address the cellular basis of tumour initiation. In particular, they are interested in understanding how mechanisms of natural injury-induced cellular reprogramming become subverted during the early stages of tumour development, with ongoing studies in tissues of the gastrointestinal tract, lung, and the brain. Going forward, the group is placing increasing emphasis on the study of developmental programmes in human epithelia, making use of advances in stem cell-derived 3D organ culture models.

Cell lineage tracing in the stomach corpus (Juergen Fink and Seungmin Han)

Simons Group photo 

　

Key Publications