HUGO SNIPPERT
Functional heterogeneity in cancers
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.
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 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.
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.
Hugo received new funding from KWF (€820k), the Dutch Cancer Foundation, to strengthen our team with two new PhD students. We will use this support to make a deep dive into the tumor microenvironment of invasive fronts at the earliest stages of colorectal cancer formation.
Hugo received a prestigious ERC consolidator grant (€2,0M) from the EU in support of our studies to understand the evolution of the tumor genome during the earliest formation of colon cancer. The project will rely heavily on genome analysis at the single-cell level in both tumors and multi-regional organoid derivatives that are representatives for sequential steps in tumor progression (being normal, adenoma, cancer and invasive front). Needless to say, we will make many fluorescent knock-in & knock-out organoids, because that’s what we like 🙂
Beautiful ceremony in the Amsterdam Stedelijk Museum for modern art. AMMODO Science Award is a biannual prize for early-career scientists to continue their research line as they seem fit (€350k).
Proud to be listed among all previous recipients. Thankful to all current and past team members, and colleagues in the CMM department.
See a short video below about my team’s current interests:
Drug-resistant cells are often metabolically inactive, compromising the suitability of mostly used drug response assays on organoids. In this publication @Cell reports, we designed a novel microscopy-based drug screen that accurately distinguishes dead from alive organoids. We found microtubule-targeting agents, commonly used in clinical oncology, to eliminate RAS mutant cells resistant to effective MAPK pathway inhibition.
Superior work from Sander!!! now being tested in a clinical trial!!!
Excited that Oncode Institute will continue to support fundamental research in our fight against cancer. Needless to say, we are proud to remain a member (senior now) and ready to roar!
Maria Heinz successfully defended her thesis called ‘Cellular heterogeneity during metastatic colonization of colorectal cancer’. Her thesis was a tour de force at a complex topic, but she excellent and showed great expertise of the topic and science in general. Both her social coffee glue and intellect will be missed. We wish her all the best in her further career and life in Heidelberg, Germany.
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 is recipient of prestigious grants like HFSP young investigators grant (2018), ERC starting grant (2018), ERC consolidator (2023) and NWO VIDI (2021).
