HUGO SNIPPERT

SNIPPERT LAB

Functional heterogeneity in cancers

RESEARCH

Cells within a cancer are highly heterogeneous with respect to their phenotype and can manifest distinct morphological, molecular and functional features. As a consequence, it is challenging to design treatment therapies that target all cancer cells as effectively. Currently, the Snippert group main interest is to use patient-derived (cancer) organoids and advanced imaging to study cellular phenomena that have a large impact on human cancer treatment.

Genetic heterogeneity

The vast majority of tumors is genetically heterogeneous, meaning that cancers are composed of many different genetic subclones. In recent years, continuous innovation in sequencing techniques has been the main driver to advance our knowledge about genetic heterogeneity in cancers. Unfortunately, little is known about tumor evolution at cell cycle resolution.

Phenotypic heterogeneity

Phenotypic heterogeneity in tumors includes non-genetic processes, such as different cell fates and phenotypes due to variable expression patterns. These are either established by tumor intrinsic cues, e.g. cellular differentiation hierarchy, or upon interaction with the tumor microenvironment.

The exact interplay between genetic and non-genetic factors remains elusive with respect to tumor growth, progression and therapy resistance.

(Single-cell) drug response

Regularly, anti-cancer therapies are effective against the majority of tumor cells. Unfortunately, there is frequently a small population of cells that shows resistance against the applied therapy. Little is known about the nature and origin of these resistant cells.

NEWS

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Health~Holland grant

Proud to be one of the seven projects in the Organ-on-Chip Showcases call that have been awarded a grant by Top Sector Life Sciences & Health (Health~Holland). I will continue to explore the use of microfluidics (from industrial partner VyCAP) with live-cell imaging of organoids to study tumor evolution.

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PhD defense Koen Oost

Koen successfully defended his thesis called ‘Cell fate dynamics in intestinal homeostasis and cancer’. He is now gone to the lab of Jacco van Rheenen (NKI, Amsterdam) in preparation to his upcoming adventure in the lab of Prisca Liberali (FMI, Basel). We wish him all the luck in science and life.

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Chromosomal instability in Nature Genetics

Our collaborative study with the Kops laboratory is published in Nature Genetics. We performed detailed live-cell microscopy on patient-derived tumor organoids from colorectal cancer patients, to study chromosomal instability levels and cell fate options after erroneous divisions in correlation to karyotype evolution. Among others we show that chromosomal instability is prevalent and ongoing in CRCs, including those designated as hypermutated (microsatellite instable). Great work by Ana and Bas.

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More organoids in Nature Medicine

Fantastic work from the Kloosterman and Clevers laboratories in Nature Medicine about the development of a new platform for the culture of ovarian cancer organoids. Nizar worked hard on the drug screening of these organoids to support the claim that these organoids can assist in personalized therapy design as well as drug development in a pre-clinical setting.

Dr. Hugo Snippert  is Group Leader at the department of Molecular Cancer Research within the Center of Molecular Medicine at the University Medical Center Utrecht. In 2017 he became an Oncode Investigator.
Hugo received his PhD (cum laude) in the lab of Hans Clevers (Hubrecht Institute) where he used advanced mouse genetics and microscopy to characterize (new) stem cell populations in the mouse intestine, skin and intestinal cancer.

His main interests relate to cell fate specifications and how multiple individual cells act in concert to secure tissue functioning. He is always looking for concepts and principles, with a strong emphasis on developing new technology.

He received an HFSP young investigators grant and ERC starting grant in 2018.

OUR FUNDING