Lars Jakobsson Group

Assistant professor

Lars Jakobsson

Phone: 08-524 879 68
Organizational unit: Lars Jakobssons group
E-mail: Lars.Jakobsson@ki.se

Lars Jakobsson's profile page.

Research

Angiogenesis and vascular biology

Overview

All tissues of the human body require nutrients, oxygen and the delivery of immune cells for their survival and expansion, hence vessels are present everywhere. This also brings that abnormal blood vessel function is a major component in the progression, or even development of, several diseases such as cancer, diabetic retinopathy, trauma, stroke complications, hereditary haemorrhagic telangiectasia (HHT) and ischemic heart disease. My lab is studying how the vasculature can reorganise and expand into the intricate network of arteries, veins and capillaries, to functionally meet the precise demand from tissue. In this process the interplay between the major units of the vasculature; the endothelial cells (ECs), the supportive mural cells, and their shared basement membrane (BM) is crucial. The properties of these different components also dictate the functional aspects of the vessels such as permeability and constriction/dilation. We study angiogenesis and vascular permeability in development as well as in diseases such as cancer. By utilizing fluorescent reporters with inducible genetic loss-of-function in unique combinations, we can analyse the role of the respective genes in detail. With live imaging techniques we also study the dynamics of the various processes.

We hope that our analysis will gather new information on how the components of the blood vessel wall affect angiogenesis, vascular stability and function. In turn an increased understanding of these cellular interactions may provide significant impact on the development and refinement of treatments of several diseases.

 

Interests in focus

Mural and EC interactions in vascular function

The recruitment of mural cells to the newly formed vasculature is known to be required for proper vascular function. We are currently characterizing this cellular interplay and its impact on vascular remodelling and function in various genetic models by live imaging techniques.

The Transforming growth factor beta (TGFbeta) family

The endothelial specific TGFbeta co-receptor Endoglin is required for vascular development and function. A mutation in this gene is coupled to the human disease HHT with vascular abnormalities. We are currently studying the precise mechanisms and roles of Endoglin in development and function of the brain vasculature.

Modelling retinopathy of prematurity. Pathological angiogenesis of the retina occurs as a consequence of hypoxia (low oxygen). Dysfunctional microvascular tufts (spheres of dividing endothelial cells, green) form and are tightly associated with macrophages (red/yellow). Cell nuclei are in blue.

The Basement membrane proteins, -laminins

Endothelial cells and pericytes rest on a matrix of several proteins that interconnect to form the basement membrane. Laminins are key components in the formation of the vascular BM. Alterations in the BM composition is commonly seen in tumours. Using conditional alleles we study the role of Laminins on vascular function, tumour growth and metastasis.

The lymphatics

Insufficient drainage of liquid, causing lymphedema, has severe impact on a large group of patients. These conditions are often a consequence of defective valves of the lymphatic vasculature. Extracellular proteins and their integrin receptors have been shown to affect the formation of the valves. Here we aim to investigate the role of Laminins on valve formation and architecture.

Collaborators: Christer Betsholtz, Helen Arthur, Taija Mäkinen, Arie Horowitz, Klas Blomgren, Arne Östman, Jonas Fuxe, Kristian Pietras.

 

Acknowledgements

We are very grateful for the generous contributions in support of our research provided by:

Cancerfonden, CVP@KI, EMBO, Vetenskapsrådet, Karolinska Institutet, W.K. Bowes Jr. Foundation, Jeanssons stiftelser, The Strategic Research Programme in Neuroscience

Research group

Mikhail BurmakinSenior lab manager
Lars JakobssonAssistant professor
Yi JinPostdoc
Yixin WangResearch assistant on study grant

David Kaluza Associated