Xiaohong Gu

My name is Xiaohong Gu and I am from Zhengzhou of China.  I have a medical degree and before I arrived to Sweden I worked as a medical doctor at the Department of Neurology at the Fifth Affiliated Hospital of Zhengzhou University.  I came to Sweden in 2007 and did my Master of Public Health at Umeå University and Master of Medical Biosciences (one year) at Linköping University.

With my research supervised by Professor Gunilla Westermark I aim to investigate the cellular response to amyloid aggregates.

Amyloidosis defines a group of misfolding diseases where amyloid is deposited in one or more organs, and amyloid is composed of proteins arranged in well-organized fibilar structures. The individual fibril has a diameter of about 10 nm and can only be identified in the electron microscope while the deposit itself can be detected in the light microscope after staining with Congo red or specific antibodies. Amyloid disease occurs in mammals and birds and today more than 35 different proteins have been described as amyloidogenic in human.

Islet amyloid is a frequent finding in islets of Langerhans in patients with type 2 diabetes, and in this disease the amyloid is built up by the β-cell produced peptide, islet amyloid polypeptide (IAPP). Deposition or formation of amyloid is cytotoxic and IAPP-amyloid is toxic to the β-cells and thought to be responsible for the detected β-cell loss in type 2 diabetes. Recently we established a new model on IAPP-amyloid in Drosophila melanogaster and showed that both human IAPP and the precursor protein human proIAPP form amyloid when the expression was driven by the pan neuronal driver elavGal4C155. This is in parallel to the findings in human and mouse models. However, in the Drosophila model we detected two different forms of aggregates in the fat body tissue: 1) Congo red positive aggregates and 2) highly ordered pentagonal aggregates. In collaboration with postdoc Ling Xie and Professor Klaus Leifer at Ångström lab at Uppsala we have determined the crystal packing structure of these aggregates.

Also, using the Drosophila melanogaster model we have pinpointed the intracellular response to proIAPP/IAPP aggregation by studying activation of ER-stress, chaperones, ROS-activation, apoptosis and autophagy.

A second amyloid protein included in my PhD work is transthyretin (TTR), a plasma protein responsible for transport of thyroxin and retinol binding protein. In amyloidogenesis, TTR is known to be associated with senile systemic amyloidosis and hereditary forms of amyloidosis. Development of hereditary forms of TTR-amyloidosis is linked to a great number of mutations leading to variant TTR molecules associated with various phenotypes dependent on tissue engagement. The three main forms are engagement of peripheral and autonomic nervous system leading to hereditary polyneuropathy, amyloid in the leptomeninges resulting in stroke and deposition of TTR-amyloid in the heart leading to cardiomyopathy.

I have generated Drosophila melanogaster expressing 10 different TTR variants described from human and use tissue specific expression to analyze if mutation per se can cause organ specific damages.

Relevant skills used in my study:

Drosophila melanogaster based models are important tools for my research and I have excellent skills in fly genetics, dissection and handling of flies. To be able to evaluate my results I use basic molecular biology techniques and protein chemistry. Microscopy techniques such as electron microscopy and confocal microscopy.
 


For further information about this research project please contact Xiaohong Gu