Ulf Gyllensten's research projects in human genomics and molecular epidemiology

Systems biology approach to human physiology

Stefan Enroth, Åsa Johansson, Ulf Gyllensten

We are studying the biological variation in human populations at the level of the genome, transcriptome, epigenome, and proteome. The variation is studied in pedigree-based population cohorts, with unique genetic backgrounds and life style, from the European Special Population Research Network (EUROSPAN).

The information includes full exome sequences of selected individuals and imputed exome structure for the complete population, genome-wide analyses of epigenomic state (methylation), high-resolution studies of the plasma proteome, the glycome (glycans), the lipidome, and exposure variables such as medical history, lifestyle and diet.

These multidisciplinary data is used to model the interaction between different types of biological information and address questions that have been beyond the reach for a single discipline. What is the impact of genetic and genomic variation on the plasma proteome? How can genetic, epigenetic, medical history, diet and lifestyle effects be modelled on the proteome? It also represents the first study to integrate data from these multiple layers of biological information and model their interactions and effect on human physiology.


Identification of the genetic risk factors for cervical cancer

Dan Chen, Ivana Juko Pecirep, Tao Cui, Stefan Enroth, Ulf Gyllensten
In collaboration with Emma Ivansson (UU)

Cervical cancer is caused by human papillomavirus (HPV) and both genetic and environmental risk factors contribute to persistence of an HPV infection and progression to cervical carcinoma. We have established population-based affected sib-pair (ASP) and case-control cohorts, including over 2,800 cases with cervical carcinoma and 2,000 controls to be used in the identification of genetic risk factors for cervical cancer. This represent the largest set of families with cervical carcinoma identified in the world and among the largest materials for case-control studies.

We have recently performed the first genome-wide association study (GWAS) for this disease, and this has led to the identification of pathways and individual genes associated with susceptibility to cervical cancer. We now continue with detailed genetic and functional studies of the identified pathways and genes. This project will increase our understanding of the etiology of cervical carcinoma and provide new means for development of diagnostic and therapeutic measures. 


Development of rapid and high-resolution methods for HPV typing, and their application to clinical screening of pre-stages for cervical cancer

Inger Gustavsson, Ulf Gyllensten
In collaboration with Matts Olovsson (UU)

We have developed techniques for collection of cervical smear samples (using FTA cards) and detection and quantification of HPV using real-time PCR. These methods allow for detection of individual HPV types and estimation of their titer. The method is economical, easily scalable and amendable to automation, making it suitable for use in primary and secondary screening for cervical cancer pre-stages. We are conducting studies using self-sampling and repeat-HPV typing to determine if this could be used as a strategy


Evaluation of the use of self-sampling and repeated HPV testing in primary screening for cervical cancer: a randomised study

Inger Gustavsson, Julia Hedlund Lindberg, Pernilla Quarfordt , Ulf Gyllensten
In collaboration with Karin Sanner, Matts Olovsson, Ingrid Wikström, Erik Wilander, Riina Aarnio (UU)

The organised gynaecological screening program in Sweden has reduced the incidence of cervical cancer by 50 %. To further reduce the incidence of cervical cancer, the sensitivity of the diagnostic test and coverage of screening must be improved. This can be achieved by introducing human papillomavirus (HPV) typing as the primary diagnostic test and implementing a screening system where women take the samples at their own convenience (by themselves and at home) and send it in to the lab for analysis.

The aim is this project is to study:

  1. The feasibility of using self-sampling at home for HPV testing, as an alternative to collection of samples at a mid-wife’s clinic.
  2. The use of repeated testing for oncogenic forms of HPV as the primary screening test for early detection of cervical cancer.
  3. The health-economic benefits of using self-sampling and repeated HPV testing as a basis for cervical cancer screening.


Identification of protein biomarkers for identification of with women with HPV infections that may lead to development of cervical cancer

Malin Berggrund, Stefan Enroth, Ulf Gyllensten

HPV is a prevalent virus and most infections are transient. However, a fraction of the HPV infections become chronic and are at high risk of leading to cervical cancer. In this project we are searching for protein biomarkers that could be used to identify women with a chronic infection and early stages of tumour development. The project is based on screening of candidate proteins using the OLINK PEA assay and multiple panels. Such biomarkers could be used in the follow-up or triage testing of HPV positive women.