Research group Mona Ståhle
The research comprises several core areas in dermatology and the main long-term projects include comprehensive genetic epidemiologic studies in chronic inflammatory skin diseases, basic preclinical research on skin barrier structure and function, skin cancer and UV-related skin diseases.
The projects directly supervised within my own team include two main areas, Psoriasis and Wound healing. Within these two blocks several independent but connected projects have formed. Our research is based on a fusion between clinical work at Hudkliniken Karolinska universitetsjukhuset, Solna and experimental work performed at Molecular Dermatology , CMM, Karolinska universitetsjukhuset, Solna.
Psoriasis - epidemiology, genetics and biology
Our research is part of the Karolinska Psoriasis Center which is the clinical base for treatment of psoriasis patients who need systemic treatments to control their disease. A clinical trial unit undertaking Phase II and III trials is affiliated. The laboratory where the experimental preclinical research is based is located at CMM in close vicinity to the clinical facilities. The psoriasis team includes in addition to clinicians, senior scientists, post-docs , graduate students and nurses. Several team members share their time between the laboratory and the clinic which enables a truly translational approach.
Psoriasis is a common and complex inflammatory skin disease with significant co-morbidity. The genetic basis for psoriasis is strong. Clinical heterogeneity suggests that different subtypes have distinct genetic background and respond differently to treatment. In 2000 we started a cohort of adult psoriasis patients recruited at the onset of disease, Stockholm Psoriasis Cohort (SPC). Today SPC includes close to 800 cases with an equal number of matched controls. In this project we have described clinical characteristics and triggering factors at disease onset and co-morbidities with focus on the metabolic profile and cardiovascular overrisk associated with psoriasis. The SPC cohort represents a cross-section of all phenotypes with the majority of cases being mild. A 10 year follow up will commence in 2011 which will provide valuable information on the natural disease course and development. To complement the SPC, we also study patients with severe psoriasis who receive systemic treatment and we have established a biobank from these patients with the aim to identify biomarkers for treatment response and genotype/phenotype profiles. Childhood psoriasis representing a distinct subphenotype is another interest. In addition to genetic susceptibility factors, we study inflammatory pathways during different disease phases and the putative role of microRNAs and their targets which are diffentially expressed in psoriasis.
Wound healing is a fundamental biologic process that entails a complex coordination of inflammation, cell migration, proliferation and tissue remodelling. How this physiologic process is controlled and executed is still insufficiently understood and mechanisms leading to impaired wound healing and chronic ulcers even less.
For the past few years we have focused on the role of the human cathelicidine protein , hCAP18/LL-37 in this process. We have shown that hCAP18/LL-37 is lacking in chronic ulcers and is upregulated during normal physiologic wound healing. The project is at present focused on studying molecular pathways involved in hCAP18 signaling and its role in cell migration and proliferation. One aim of this project is to develop treatments for impaired wound healing.
MicroRNA-125b Down-regulates Matrix Metallopeptidase 13 and Inhibits Cutaneous Squamous Cell Carcinoma Cell Proliferation, Migration, and Invasion.
J Biol Chem. 2012 Aug 24;287(35):29899-908. Epub 2012 Jul 10.
Genetic Association with ERAP1 in Psoriasis Is Confined to Disease Onset after Puberty and Not Dependent on HLA-C*06.
J Invest Dermatol. 2012 Aug 30. doi: 10.1038/jid.2012.280. [Epub ahead of print]
MicroRNA-203 functions as a tumor suppressor in basal cell carcinoma of the skin.
Oncogenesis, In press.
Cost-effective HLA-Cw06:02 typing in a Caucasian population.
Exp Dermatol. 2012 Mar;21(3):221-3. doi: 10.1111/j.1600-0625.2011.01423.x
Identification of the cathelicidin peptide LL-37 as agonist for the type I insulin-like growth factor receptor.
Oncogene. 2012 Jan 19;31(3):352-65. doi: 10.1038/onc.2011.239. Epub 2011 Jun 20.
MiR-125b, a microRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2.
J Invest Dermatol. 2011 Jul;131(7):1521-9. doi: 10.1038/jid.2011.55. Epub 2011 Mar 17.
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
Nat Genet. 2010 Nov;42(11):985-90. Epub 2010 Oct 17.
MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte-associated antigen 4.
J Allergy Clin Immunol. 2010 Sep;126(3):581-9.e1-20. Epub 2010 Jul 31.
Topical treatment with the vitamin D analogue calcipotriol enhances the upregulation of the antimicrobial protein hCAP18/LL-37 during wounding in human skin in vivo.
Exp Dermatol. 2010 Apr;19(4):332-8. Epub 2009 Oct 28.