Analysis of the pathological effects of light chains and AL protein states

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Systemic AL amyloidosis is a highly heterogeneous disease arising from the interactions of light chains or light chain fragments with the tissue. However, it is still poorly understood how organ- and tissue- specific environmental factors modulate disease manifestation and progression. To shed some light on these issues we will address the following aims: (i) Assessment of the light chain pathology in the heart and kidney. (ii) Analysis of the pathological effects of light chain states in model systems. (iii) Translation of the model systems into human pathology. This pro-ject will test the hypotheses that the biochemical and structural composition of tissues and or-gans impacts on the manifestation, progression and prognosis of AL amyloidosis. We will combine conventional histological, immunohistochemical and image analysis tools with highly ad-vanced mass spectrometry imaging techniques to examine the mechanism of light chain pa-thology in patient tissues. In addition we will carry out cell biological studies using cardiac and renal cells, with which we will test the pathological relevance of the specific protein states analyzed in this research unit to enable correlations between protein structural features and cellular effects. Although the scope of this project is on understanding the mechanism of light chain pathology in the heart and kidney, improvements in the monitoring of amyloid inside the tissue may have relevance for the development of novel diagnostic and therapeutic standards.