Katrin Mani

Katrin Mani

Professor, Medical degree (MD), Doctor of Philosophy in Medical Science (PhD)

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Expression, signaling, biomarker potential and prognostic value of glypicans in different cancers

Deciphering the mechanisms involved in communication between cancer cells and stroma cells, is crucial for finding new therapeutic strategies. Glypicans (glypican 1-6) are strategically positioned at the cell surface and act as co-receptors for different signaling molecules known for motility, differentiation, and regulation of cell growth. Therefore, it is not surprising that glypicans can be great biomarkers or therapeutic target candidates in various types of cancers.
We are working on systematic screening of each individual glypican for its impact in cancer progression. Using bioinformatics and different experimental models, we will study their functions in terms of growth factor signaling. Furthermore, we are investigating the impact of each glypican as a biomarker and prognostic factor in different cancer types. We use meta-analysis of data from international cancer databases including “Genome Wide Atlas”, containing information on gene expression patterns and cancer progression from a cohort of patients, with different aggressive cancer forms. Moreover, we are elucidating the impact of glypicans in cancer progression, by in vitro gene silencing studies using CRISPR/Cas9 and by overexpression studies.

Glypican-1, an amyloid cofactor: Is glypican-1 an amyloid deposit antagonist?

Glypican-1 is the major heparan sulfate proteoglycan (HSPG) in the adult human brain. Modulation of glypican-1 processing affects Alzheimer’s disease (AD), development in both familial AD and in sporadic AD. This includes ApoE-mediated AD, Niemann-Pick C disease and AD, inflammation-related AD pathology and the environmental neurotoxin BMAA-triggered AD pathology. According to our results in in vitro studies and ex vivo brain tissue studies, ascorbate-induced, copper/nitric oxide (Cu/NO)-dependent release of heparan sulfate (HS) from glypican-1, can suppress accumulation of amyloid β in AD and modulate cellular trafficking of α-synuclein in Parkinson’s disease (PD). HS also decreases intracellular accumulation and increases secretion of α-synuclein filaments in in vitro PD models. Furthermore, HS can inhibit APP processing, form complexes with amyloid β (Aβ), inhibit Aβ oligomerization, and target APP degradation products (β-CTF/Aβ) to autophagosomes/ lysosomes. 

We plan to investigate the effect of glypican-1 processing in β-CTF/Aβ and α-synuclein accumulation in novel in vivo mouse models of sporadic forms of the diseases. An important disparity with regard to mouse models is that humans, in contrast to mice, are unable to synthesize ascorbate. Using wild-type mice, ApoE4+/+ mice (that express the ApoE4 risk factor) and GulO-/- mice (lack L-gulonolactone oxidase (GulO) and are therefore unable to synthesize ascorbate), we will generate a novel humanized mouse model for these dieseases, by cross breeding ApoE4+/+ and GulO-/- mice. The effect of treatments that increase the capacity to generate HS from glypican-1, including supplementation of the diet with ascorbate, dehydroascorbic acid, NO-donors, enrichment with L-arginine (NO-precursor) or L-serine, will then be investigated using amyloid-PET/MRI and histopathological studies. All these agents are non-toxic, inexpensive, and can cross the blood-brain barrier.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

UKÄ subject classification

  • Cancer and Oncology
  • Neurosciences

Free keywords

  • Proteoglycan
  • Glypican
  • Growth factors
  • Cancer
  • Neurodegenerative diseases
  • Alzheimer's disease
  • Parkinson's disease


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