Walter HUNZIKER

Epithelial Cell Polarity in Disease and Tissue Regeneration Laboratory

PhD – Natural Sciences, Swiss Federal Institute of Technology, Zürich

Linked: https://www.linkedin.com/in/walter-hunziker-24982615/

SUMMARY

Dr. Walter HUNZIKER is a Research Director at the Institute of Molecular and Cell Biology (IMCB) and Adjunct Research Professor at the Department of Physiology, National University of Singapore. He obtained his PhD from the Swiss Federal Institute of Technology (Zurich) in Natural Sciences in 1986. He completed his postdoctoral training at Yale University School of Medicine, where he worked with Dr. Ira Mellman. He then held research positions at Yale University and the University of Lausanne before joining IMCB in 2000.

Dr. Hunziker's research focuses on the molecular mechanisms regulating epithelial cell polarity, tight junctions, and membrane traffic. He is particularly interested in understanding how these processes contribute to human diseases such as cancer, cardiovascular and metabolic disorders. His laboratory uses animal and tissue culture models with a combination of biochemical, cell and molecular biological, and imaging approaches to study the composition and regulation of tight junction dynamics in polarized epithelial cells. By elucidating the underlying mechanisms, his research aims to identify novel therapeutic targets for the treatment of diseases associated with epithelial dysfunction.

AWARDS & GRANTS

1992-02: Leenaards Foundation Career Development Award
1992-99: Swiss Talents in Research and Teaching (START) Career Development Award
1991: Swebilius Cancer Research Award
1987: Swiss National Science Foundation Fellowship (declined in favor of Damon Runyon Fellowship)
1987: EMBO Fellowship (declined in favor of Damon Runyon Fellowship)
1987: Damon Runyon-Walter Winchell Cancer Research Fellowship
1987: Anna Fuller Foundation Fellowship
1987: ETH Medal, Swiss Federal Institute of Technology, Zürich

RESEARCH

Tight junctions play a crucial role in maintaining the structural and functional integrity of cell layers in various organs and tissues. In epithelia that face the external environment (e.g. skin, GI tract), tight junctions form protective barriers. Within organs, they serve as ion selective barriers that maintain the distinct physiological milieu of particular tissue compartments (for example the bood-bile barrier in the liver, the inner and outer blood retinal barrier in the eye, the blood-brain barrier, the glomerular and tubular barriers in the kidney). Tight junctions are also critical for maintaining the polarized distribution of plasma membrane proteins such as transporters and enzymes to the apical or basolateral surfaces of epithelial cells.

Our research aims to understand the role of tight junctions in health and disease at the molecular, cellular, and tissue level using pre-clinical animal models. A particular interest is to understand the emerging role of tight junctions as signaling platforms and elucidate novel functions for their constituents, for example in tissue regeneration. Specifically, we focus on the role of tight junctions in liver, retinal and cardiovascular physiology and their dysregulation in disease. Our work aims to uncover new avenues for preventing and treating disease and has led to the identification of potential therapeutic targets and approaches.

PUBLICATIONS

ZO-2/Tjp2 suppresses Yap and Wwtr1/Taz-mediated hepatocyte to cholangiocyte transdifferentiation in the mouse liver
J Xu, PJ Kausalya, AGM Ong, CMF Goh, S Mohamed Ali, W Hunziker
NPJ Regenerative Medicine 7 (1), 55
Protective functions of ZO-2/Tjp2 expressed in hepatocytes and cholangiocytes against liver injury and cholestasis
J Xu, PJ Kausalya, N Van Hul, MJ Caldez, S Xu, AGM Ong, WL Woo, ...
Gastroenterology 160 (6), 2103-2118
Early embryonic lethality of mice lacking ZO-2, but Not ZO-3, reveals critical and nonredundant roles for individual zonula occludens proteins in mammalian development
J Xu, PJ Kausalya, DCY Phua, SM Ali, Z Hossain, W Hunziker
Molecular and cellular biology 28 (5), 1669-1678
Glomerulocystic kidney disease in mice with a targeted inactivation of Wwtr1
Z Hossain, SM Ali, HL Ko, J Xu, CP Ng, K Guo, Z Qi, S Ponniah, W Hong, ...
Proceedings of the National Academy of Sciences 104 (5), 1631-1636
Disease-associated mutations affect intracellular traffic and paracellular Mg2+ transport function of Claudin-16
PJ Kausalya, S Amasheh, D Günzel, H Wurps, D Müller, M Fromm, ...
The Journal of clinical investigation 116 (4), 878-891 240 2006
Quantitative proximity proteomics resolves the epithelial apical-lateral border and uncovers a vertebrate marginal zone defined by the polarity protein Pals1
B Tan, S Peng, S Sandin, J Gunaratne, W Hunziker, A Ludwig
Current Biology 30:2791-2804.

PATENTS

Modulating the interaction between ZO-2/TJP2 and a Snail zinc finger transcription factor family member (US9963704B2)
This patent describes a method of identifying candidate agents capable of modulating the interaction between ZO-2/TJP2 and a Snail zinc finger transcription factor family member, which can be used to regulate cellular processes such as cell proliferation, differentiation, and survival. The invention provides a novel approach for identifying potential therapeutic agents for diseases related to aberrant cell behavior.
Modulation of TJP1 expression to regulate regeneration of heart cells (US11820981B2)
This patent describes a method for treating heart disease, particularly acute myocardial infarction (AMI), by administering a Tjp1 inhibitor to promote cardiomyocyte proliferation. The invention also includes the use of Tjp1 inhibitors in combination with other factors, such as Neuregulin-1 (NRG1), Fibroblast growth factor (FGF), Vascular endothelial growth factor (VEGF), or Follistatin-like 1 (Fst1), and delivery via adeno-associated virus of serotype 9 (AAV9). This approach aims to enhance cardiac regeneration and repair after injury.

Walter HUNZIKER

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