Project IX

Regulation of osteoclast subsets by systemic and local factors.

Laia Mira Pascual

I am Laia Mira and I am from Pedreguer, a little city in the south-east part of Spain, close to the Mediterranean Sea. I did my Biology degree at the University of Valencia and I did the Master in Biomedical Biotechnology at the Polytechnic University of Valencia. My Master´s thesis project was performed at the Institute of Food Technology and Agrochemistry and was focused on detecting biomarkers in the prevention of colon cancer. In my free time I enjoy travelling, spending time with my family and hanging out with my friends. Besides these, my hobbies are going to the beach and sunbathing, and hiking and afterwards having a nice lunch in the mountain.

Since the middle of June 2014 I am working as an Early Stage Researcher and graduate student in Stockholm (Sweden) at the Pathology division of Karolinska Institutet. I can be reached by email on: laia.mira.pascual@ki.se

Göran Andersson

I am professor of Pathology at Karolinska Institutet Huddinge campus since 1998. Besides research I participate in undergraduate teaching for medical, dental, biomedical, biomedical technology and nursing students in various aspects of molecular, cell, tissue biology and pathology.

I am at present head of the division of Pathology and vice chairman of the Department of Laboratory Medicine. I have supervised 14 PhD students to completion and am currently supervising 2 PhD students as the main supervisor.

My research focuses on bone-resorbing osteoclasts and in particular the structure and function of the enzyme tartrate-resistant acid phosphatase (TRAP), a well-known cell marker for osteoclasts. More information on my group can be found at http://ki.se/en/labmed/research-group-goran-andersson

Pernilla Lång

I am Pernilla Lång living in Södertälje a town close to Stockholm. I have a bachelor degree in laboratory science and a PhD in experimental pathology from Karolinska Institutet where I am currently working as a lecturer and researcher.

My main research focus has been to study how the protein tartrate-resistant acid phosphatase acts as a growth factor on cells of mesenchymal origin i.e. osteoblast and adipocytes. When I am not working you will find me hiking with my dogs or digging in the garden. You can reach me at pernilla.lang@ki.se.


Our Project

Disturbance of the normal skeletal homeostasis has profound effects in health affecting bone quality. Many of these disturbances are due to malfunctioning osteoclasts (OCs). Around 10 years ago OC heterogeneity was described for the first time. It was suggested that OCs might originate from different precursors, but also that  site-specific  microenvironments (cells, cytokines, matrix molecules) could contribute to the heterogeneous characteristics exhibited by site-specific OC. Site-specific OC appear to differ in for example the machinery responsible for resorption and in their potential to absorb drugs. The general aim of this doctoral thesis ´´Regulation of osteoclast subsets by systemic and local factors´´ is to investigate how OC physiology is affected by different precursors and different microenvironments.

During the project, we will analyse both morphological- and molecular characteristics of OC subtypes in order to further our understanding of OC heterogeneity and how it affects OC physiology to contribute to the treatment of bone pathology. We will analyse differences between OC subtypes, e.g., whether they are multinucleated or mononucleated, analyse morphological features such as size, shape and membrane protrusions and study expression of signature molecules for osteoclast and macrophage differentiation such as tartrate resistant acid phosphatase (TRAP). We will also examine the ruffled border and sealing zone, functionality of the acidification complex and ability to resorb bone.

The aim of the molecular characterization is then to identify which molecular events are responsible for the heterogeneity of osteoclast populations using a variety of techniques.

Left to right: Pernilla, Göran and Laia