Protein degradation pathways – Helin Norberg's research group

The focus of the lab is to dissect the cells own quality control mechanisms to develop novel therapeutic strategies to selectively target pathogenic proteins in cancer or other human disorders. To this end, the group study the molecular details of various fundamentally different protein degradation mechanisms, involving the autophagy-lysosome pathways. The lab encompasses full spectrum of investigations on both basic research and highly translational efforts using patient and animal experiments.

Researcher in lab with her back against the camera

Research at Helin Norberg lab

The Norberg lab current research focuses on Chaperone-mediated Autophagy (CMA), a unique type of mammalian autophagy that only applies to proteins without affecting cellular organelles.

Illustration of Chaperone-mediated Autophagy (CMA), a unique type of mammalian autophagy that only applies to proteins without affecting cellular organelles
Figure legend: Schematic illustration of used methodologies and approaches in the group in respect to current CMA research projects.

Over the recent years, the Norberg lab has explored new therapeutic approaches by stimulating the cell’s own quality control mechanisms to induce the degradation of pathogenic proteins to prevent their aberrant accumulation. More recently, the lab has been dedicated on developing a new field of `Controlled Autophagic Proteostasis' by studying the autophagy-lysosomal pathway. Therefore, the current research focuses on Chaperone-mediated Autophagy (CMA), a unique type of mammalian autophagy that only applies to proteins without affecting cellular organelles.

The role and impact of CMA in Cancer

Proteins that promote tumor growth and dissemination are often mutated, deregulated and distinctively stabilized in cancer cells. As pathogenic accumulation of these proteins effectively sustains cancer progression, they represent indisputable targets for treatment. Hence, understanding how these proteins can be removed is of great importance for improved cancer therapy. The goal of this project is therefore, to study mechanisms of protein degradation by CMA to understand a) the implication of recruiting the unique type of mammalian autophagy to specifically promote lysosomal degradation of oncoproteins, b) to identify novel CMA targetable oncoproteins, c) the impact of degrading oncoproteins by CMA.

To explore the impact of CMA activation

The role of CMA in cancer cells remain paradoxal and the physiological importance of CMA in cancer is currently not defined. Therefore, this project intends to investigate the CMA pathway in depths both at cellular and organismal level, in order to explore the intriguing possible role of activating CMA in various human malignancies to find selective targeted approaches applicable for pathogenic proteins. Further the project aims to understand the underlying molecular mechanisms of CMA activation and its oncogenic and pathogenic targeting. Ultimately, we aim to explore the impact of CMA activation in vivo.

The role and impact of CMA in human disorders

The findings from the above-mentioned projects will provided with answers to address a long-standing question in cell biology; How is CMA activated and regulated in cells? However, although the answers to these questions will provide us with a detailed molecular understanding of a fundamental biological process, we still need a comprehensive understanding of the role of CMA in various medical conditions as a basis for proposing new treatment strategies. Therefore, this project, is design to understand the role and impact of CMA in proteopathies and multiple other human diseases. This project has a translational focus which enables a tremendous potential to open up new therapeutic avenues and biomarkers.

News from Helin Norberg lab

Publications

Selected publications

  • Article: METHODS IN MOLECULAR BIOLOGY. 2022;2445:39-50
    Yu T-T; Zhou X; Vakifahmetoglu-Norberg H
  • Article: AUTOPHAGY. 2021;17(11):3865-3874
    Kacal M; Zhang B; Hao Y; Norberg E; Vakifahmetoglu-Norberg H
  • Article: CELL DEATH AND DIFFERENTIATION. 2021;28(3):1091-1109
    Krassikova L; Zhang B; Nagarajan D; Queiroz AL; Kacal M; Samakidis E; Vakifahmetoglu-Norberg H; Norberg E
  • Review: AUTOPHAGY. 2021;17(1):1-382
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    Queiroz AL; Vakifahmetoglu-Norberg H; Norberg E
  • Article: MOLECULAR AND CELLULAR BIOLOGY. 2017;37(24):e00328-e00317
    Eriksson M; Ambroise G; Ouchida AT; Lima Queiroz A; Smith D; Gimenez-Cassina A; Iwanicki MP; Muller PA; Norberg E; Vakifahmetoglu-Norberg H
  • Article: CELL REPORTS. 2017;19(11):2289-2303
    Zhang B; Zheng A; Hydbring P; Ambroise G; Ouchida AT; Goiny M; Vakifahmetoglu-Norberg H; Norberg E
  • Article: JOURNAL OF CANCER. 2017;8(11):2088-2096
    Zhang B; Tornmalm J; Widengren J; Vakifahmetoglu-Norberg H; Norberg E

Members and contact

Group leader

All members of the group

Visiting address

Karolinska Institute, Solnavägen 9, Biomedicum, Solna, 171 65, Sweden

Postal address

Karolinska Institute, Physiology and Pharmacology, Attn: [Name of recipient], Stockholm, 171 77, Sweden

Picture of Helin Norberg lab's group members, standing next to eachother in Biomedicum.
From left to Right: Vitaly Kaminsky (Researcher), Xun Zhou (Postdoc), Yong Shi (Postdoc), Helin Norberg (PI), Aironas Los (Bachelor Student), Merve Kacal (PhD student, Ellen Olerup (Medical Student). Photo: Elena Kochetkova

Co-supervision

Lisa Benrejdal – PhD student (Assoc Prof. Peter Bergman Lab, Dept of Laboratory Medicine. KI) (Co-supervisor).

Alumni

Tingting Yu – Guest researcher, now Assistant Professor (Nanjing Medical University, China).

Amanda Ouchida – Postdoctoral researcher, now at Albert Einstein College of Medicine, NY, USA.

Adi Zheng – Postdoctoral researcher, now at University of Lausanne, Switzerland.

Yuqing Hao –  Postdoctoral researcher, now researcher at BeiGene, China.

Tao Cui – Postdoctoral researcher, now researcher at Novartis, China.

Gorba Ambroise – Postdoctoral researcher.

Mathilda Eriksson – Lab manaher, now Research engineer (KI).

Davide Chiesi – Masters student, now at Novartis, Switzerland.

Kristin Uth – Project student, now PhD student (Bern, Switzerland).

Available positions

  • We are seeking for a highly motivated and innovative postdoctoral scientist.
  • We welcome applications from well-qualified Masters students.

How to find us