Biography

My research has a strong multi-disciplinary approach. I have progressed from in silico, to in vivo into the clinic and back again over the last decade. This has been possible because of the focus I have placed on building my network of collaborators. In particular, in collaboration with leading experts I investigated:

1. Proteasome-catalysed peptide splicing (PCPS)
I studied PCPS mechanisms and relevance in antigen presentation, thereby:
o discovering that PCPS is much more frequent than expected;
o proving that PCPS triggers T cell response in cancer and infection;
o identifying the first spliced neoepitope (carrying KRAS G12V mutation);
o proving that PCPS is driven by specific factors, which affect also the antigenic spliced peptide motifs;
o developing novel methods for spliced peptide identification by mass spectrometry.
Selected papers: Liepe et al., Science 2016; Platteel et al., Cell Rep. 2017; Mishto et al., Front. Immunol. 2019.
Patents:
o “T cell receptors for tumor specific proteasome splice variants and uses thereof”. PCT/EP2019/050027 (02/01/2019).
o “Method for identification of proteasome generated spliced peptides”. EP 10075087.6 (25/02/10).

2. Proteasome isoform proteolytic dynamics
I characterised the proteolytic activities of standard-, immuno-, and thymo-proteasome by combining biochemistry and computational biology.
Selected papers: Mishto et al., Eur. J. Immunol. 2014; Kuckelkorn et al., JBC 2019.

3. Immunoproteasome in neurological diseases and ageing
I was the first to demonstrate the expression of immunoproteasome in Alzheimer disease, epilepsy, multiple sclerosis. I studied its role in neuroinflammation and its expression upon ageing.
Selected papers: Mishto et al. Neurobiol. Ageing 2006; Mishto et al., BBRC. 2011.

4. Proteasome as part of the immune system
I studied the role of proteasomes in regulating the immune response during (neuro)inflammation.
I was the first to define a role of the extracellular proteasomes in regulating inflammatory pathways.
Selected papers: Mishto et al., Brain, Behav. Immunol. 2015; Dianzani et al., Sci. Res. 2017.

5. Computational modelling and in silico method development
I worked with bioinformaticians and computational biologists to develop computational models of proteasome and osteopontin dynamics, protein degradation and immune system as well as developed the first methods for the identification and quantification of spliced peptides in various experimental models.
Selected papers: Liepe et al., eLife 2015; Liepe et al., Cancer Immunol. Res. 2019.