CanCell Affiliate Members
Kay Oliver Schink and Helene Knævelsrud
Front row (left to right): Sampada Satchidanand Bhagwat, Klaudia Orlowska, Siri Andresen, Birgit Kriener, Paulina Schnur, Julie Aarmo Johannessen. Back row (left to right): Aina Louise Cimafranca Haukeland, Helene Knævelsrud, Robin Scheler-Eckstein, María Hernandez Mesa, Eline Bjørnsdatter Hoddevik Hernes. Photo: Ine Eriksen, UiO.
We work on understanding the regulation of autophagy in physiology and disease
The Cell stress and Cancer group is focused on two main goals: to understand how autophagy is switched off in vivo and to unravel mechanisms of autophagy involvement in cancer biology. We make use of model organisms as well as primary material from cancer patients to study several basic problems in autophagy and cancer.
Cells in a living organism need to be able to readily respond to changes in nutritional status. Upon starvation, certain tissues respond by autophagy, to provide energy and building blocks to sustain essential cellular functions. Importantly, these cells must also turn off autophagy when nutrient supplies are replenished, because unrestricted autophagy is harmful to cellular fitness. Surprisingly little is known about how autophagy is terminated, especially in the context of a multicellular organism. We work on uncovering and understanding novel mechanisms of autophagy termination, using Drosophila as a model.
In terms of cancer, we are investigating whether autophagy can be exploited as biomarkers or therapy targets in kidney cancer. Each year close to 1000 people are diagnosed with kidney cancer in Norway. Whereas localized cancer can be cured by surgery, the challenge is to identify which patients will progress to metastatic cancer and also to identify the best treatment for each of those patients. We are working on the use of markers of autophagy to address these needs in different subtypes of renal cell carcinoma and also in the inherited predisposition for renal cancer associated with Birt-Hogg-Dubé syndrome.
In addition to sharing data with the scientific community, we are engaged in public outreach. Examples from 2025 include: Helene Knævelsrud presented about her involvement in user panels for basic research at several occasions: EUnetCCC (European Network of Comprehensive Cancer Centres) meeting in May 2025, patient day at MIK/CRESCO in August 2025 and at a meeting for early career scientists about user involvement organized by the Norwegian Cancer Society in November 2025. Helene Knævelsrud was also featured together with Anne Simonsen from CanCell in the Norwegian Cancer Society Magazine “Felles Krefter” about the future of cancer research.
Projects
- Final act of the autophagy symphony: Whole-organism orchestration of autophagy termination – FINALphagy (ERC StG 2023-2027)
- Metabolic control of autophagy termination (UiO internal funding 2024-2028)
- AUTORHYTHM – the role of autophagy in healthy aging (UiO Life Science convergence environment 2022-2026)
- Unraveling the role of autophagy in kidney cancer (South-Eastern Norway Regional Health Authority, 2022-2026)
- Autophagy as a phylogenetically conserved mediator of sleep benefits (NCMM Joint Postdoctoral Programme 2025-2027)
- Development of a platform for personalized treatment decisions for Renal Cell Carcinoma. (South-Eastern Norway Regional Health Authority, Innovation grant, 2025-2026)
- Decoding and disabling the FLCN-TFEB axis in Birt-Hogg-Dubé syndrome (Peder Sæther grant with Roberto Zoncu, UC Berkely, 2025-2026)
Highlights
- Andresen S, Al Outa A, Formica M, Enserink J, Knævelsrud H.: Improved detection of lipidated Atg8a by immunoblotting in Drosophila melanogaster cells and tissues enables precise investigation of Atg8a flux and its termination. Autophagy. 2025 Nov;21(11):2497-2517.
- Ullern H, Schnur P, Boccara CN, Knævelsrud H.: Rest, Repair, Repeat: The Complex Relationship of Autophagy and Sleep. J Mol Biol. 2025 Sep 15;437(18):169227.
- Presacan O, Hernández Mesa M, Aldea AC, Andresen S, Al Outa A, Aarmo Johannessen J, Ionescu B, Knævelsrud H, Riegler MA.: Explainable AI to unveil cellular autophagy dynamics. PLoS One. 2025 Sep 11;20(9):e0331045
- Helene Knævelsrud presented at the flyJEDI meeting outside Paris in June 2025
- Helene Knævelsrud was invited to present at the 10th NO-Age/AD meeting cum the 3rd Norway-UK meeting on Ageing and Dementia in Oslo in November
- Helene Knævelsrud obtain an innovation grant from South-Eastern Norway Regional Health Authority for the Development of a platform for personalized treatment decisions for Renal Cell Carcinoma.
Membrane Trafficking Group
Cells depend on an internal membrane-based “logistics system” that moves proteins, lipids, and nutrients between specialized compartments. This trafficking only works if each vesicle acquires the correct identity at the right time - otherwise cargo is misrouted, compartments lose function, and cells drift into pathological states.
My group studies the principles that generate and maintain membrane identity, with a strong focus on large-scale fluid uptake (macropinocytosis) and its coupling to cancer cell metabolism and invasive behavior.
Many tumors exploit macropinocytosis to access extracellular nutrients in poorly perfused tissue. We ask how this uptake program is organized, how vesicle identity transitions are executed and safeguarded, and how these rules shape tumor growth, therapy response, and metastasis.
Current research directions
- Spatial control of macropinocytosis. Macropinocytosis does not occur uniformly across the cell surface. Cells often reuse discrete membrane zones where large vesicles repeatedly form. Using controlled cell geometry and quantitative live-cell imaging, we test how physical and spatial cues define these uptake hotspots and how cells sustain repeated rounds of large-scale fluid uptake without destabilizing membrane homeostasis.
- Establishment and maintenance of membrane identity. A newly formed macropinosome originally inherits plasma membrane identity, but it must rapidly establish endosomal identity to enter the endosomal system and mature. We study this as a time-resolved identity transition, asking how identity determinants are acquired, stabilized, and handed over during maturation. In parallel, we dissect quality-control mechanisms that detect failed identity conversion and reroute aberrant vesicles, preventing long-lived, mis-identified compartments from accumulating.
- Linking nutrient scavenging to invasion and metastasis. In nutrient-poor tumors – particularly pancreatic cancer - cells must balance nutrient acquisition with migration and tissue invasion. We investigate how uptake and trafficking programs interface with invasive behavior, and how trafficking-state decisions bias cells toward “feeding” versus “moving” phenotypes. A key goal is to identify regulatory bottlenecks that can be targeted to weaken tumor adaptation in hostile microenvironments.
- Self-organization principles in organelles. Beyond endocytic trafficking, we are interested in how organelles create internal subdomains that separate distinct biochemical routes. This line of work connects membrane logistics to a broader principle: spatial organization inside organelles can be an active strategy to maintain robustness and prevent cross-talk between incompatible reactions.
Projects
- Cellular control of macropinosome formation and maturation (FriPro grant, Research Council of Norway, 2021–2027)
- Identity generation in cellular membrane systems (UiO internal funding)
- Novel regulators of macropinocytosis to disrupt cancer nutrient supply routes (South-Eastern Norway Regional Health Authority, 2023–2026)
- “Drink or drive” – Regulation of cell invasion and metastasis by macropinocytosis (The Norwegian Cancer Society, 2024–2027)
Highlights and outreach
- Kay Oliver Schink presented our pancreatic cancer work on nutrient scavenging and invasion at the annual network meeting of the Norwegian Cancer Society’s National Group of Expertise for Research on Pancreatic Cancer (KNEP).
- Lisette Sandoval presented our work at the EMBO Cell Polarity and Membrane Trafficking meeting.
- In an interdisciplinary collaboration published in Nature Communications (2025), we showed that peroxisomes self-organize core structures that segregate distinct metabolic pathways, revealing a general principle for robust organelle function.
