Genetics and epigenetics of sarcoidosis.
I am a human geneticist, and my research focuses on the genetics and epigenetics of sarcoidosis and rheumatoid arthritis.
My research endeavors to study disease molecular mechanisms from a broad angle with high-throughput genomic data coupled with clinical and environmental / lifestyle data. Chiefly, I carry out research investigations in multiple population-based cohorts through the MESARGEN consortium to unravel molecular factors implicated in disease pathogenesis and identify clinical biomarkers across populations.
Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology. The disease predominantly affects the lung; however other organs can be affected as the disease progresses and with up to 20% of patients developing fibrotic lung disease (i.e., pulmonary fibrosis). The disease occurs worldwide, varying with prevalence and clinical course across populations of different ancestries. Northern Europeans and African Americans are the most susceptible to the development of the disease and predominantly women. Individuals affected by sarcoidosis are between 30 and 60 years of age.
Several disease features, such as the variability in the clinical presentation and lack of case definitions, pose a challenge for its diagnosis, which is further compromised by the lack of specific diagnostic biomarkers. To date, there are no biomarkers that enable a definitive diagnosis of the disease. Like many complex autoimmune diseases, sarcoidosis has a genetic component that underlies the disease pathogenesis and implicates molecular dysfunctions in the homeostasis of the immune system that are likely caused by environmental factors and lifestyle exposures in genetically predisposed individuals. Therefore, to identify the disease mechanisms underlying sarcoidosis pathogenesis, it is first central to recognize molecular determinants in the disease.
Our group focuses on genomic investigations of sarcoidosis and rheumatoid arthritis. Our vision is to decipher the molecular mechanisms underlying disease pathogenesis and chronic inflammation implicated in autoimmunity. Our work is mainly data-driven with high-throughput genomic data compounded with statistical genetics, bioinformatics, and cutting-edge statistical approaches.
Using genomic data collected by MESARGEN in 6 European populations with appropriate controls (Sweden, Greece, Spain, Portugal, Czech Republic, and The Netherlands), we aim to explore the opportunity for biomarker discovery, thereby conducting genome-wide screening in multi-ethnic cross-sectional cohorts, to understand how genetic variation underline disease architecture of sarcoidosis. Moreover, genetic information combined with epigenomic and transcriptomic data and environmental / lifestyle exposures will provide a more precise and predictive approach for identifying genomic signatures (“biomarkers”) in sarcoidosis.
Our long-term goal is to identify clinical biomarkers and molecular disease targets that can help clinicians with better diagnostic and prognostic tools. Specifically, we envision applying genomic signatures to classify individuals susceptible to disease and those with increased risk for adverse disease outcomes. Deciphering the molecular networks underlying sarcoidosis pathogenesis will lead to a better understanding of the disease and, eventually, the development of more realistic gene-based therapies in sarcoidosis. MESARGEN – Multi-Ethnic Sarcoidosis Consortium for Genetic Studies was established in 2016, and it is the most extensive international framework in Europe dedicated to genomic investigations and translational research in sarcoidosis. The Swedish Heart-Lung Foundation funds it.
Leo Daniel Gkekos, master student
Olga Chuquimia, research engineer
Patrick Kanyi Ndungu, master student
Ying Xiong, master student
Tomoko Iseda, research assistant
Zdenka Navratlova, postdoc
Christine Scerbo, summer student
Muntasir Abo Al Hayja, doctoral student
Vasiliki Vasila, research assistant
Karina Patasova, master student
- Basic statistical genetics and data visualization, course number 5308, spring 2022
- Pulmonary inflammation, course number 3145 (1.5 p), spring term 2019
- Basic course in bioinformatics, course number 3044 (1.5), spring term 2018 and 2019
PhD in Molecular Medicine, Feb 2012. Dissertation title: "Genetics of Left Ventricular Hypertrophy". Doctoral School of Molecular Medicine, University of Milan, Segrate, Milan, Italy
Master of Science in Health Sciences - Specialization Genetic Epidemiology, Sept 2011. Thesis title: "Assessment of 9p21.3 locus with severity of Coronary Artery (CAD) in the presence and absence of Type 2 Diabetes". Netherlands Institute for Health Sciences (NIHES), Erasmus University Medical Center Rotterdam, The Netherlands
Master of Science in Electrical Engineering, Jan 2005. Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
Bachelor of Science in Electrical Engineering, Dec 1999. Syracuse University, Syracuse, New York, USA
Academic honours, awards and prizes
Funding as main applicant (Principal Investigator)
- 2021 – 2022 Project grant “Integration of omics data to identify potential drug targets in sarcoidosis”, Svensk Lungmedicinsk Förenings (SLMFs) Lung Medicine Research Grant (250,000 kr)
- 2021 -2022 Project grant "Epigenetic markers of ocular sarcoidosis", KI Stiftelser och Fonder, Stockholm, Sweden (60,000 kr)
- 2021 – 2023 Project grant “Molecular biomarkers of sarcoidosis using MESARGEN, a multi-ethnic population-based consortium”, Swedish Heart and Lung Foundation, Stockholm, Sweden (2,100,000 kr)
- 2021 – 2023 Research months “Discovery of clinical biomarkers in organ-specific sarcoidosis phenotypes via the integration of genome, transcriptome, and methylome coupled with lifestyle and environmental exposures”, Swedish Heart and Lung Foundation, Stockholm, Sweden (711,000 kr)
- 2021 – 2022 Project grant “The integration of genetic data and environmental factors including lifestyle exposures in sarcoidosis”, KI Stiftelser och Fonder, Stockholm, Sweden (90,000 kr)
- 2020 - 2022 Project grant “Blood and lung-based DNA methylation in pulmonary sarcoidosis: Biomarker discovery and potential drug targets for clinical applications”, Swedish Medical Society, Stockholm, Sweden (250,000 kr)
- 2019 - 2020 Project grant “Genetic markers for diagnosis of sarcoidosis”, Tore Nilsons Foundation for Medical Research, Stockholm, Sweden (50,000 kr)
- 2019 - 2020 Project grant “Molecular biomarkers of sarcoidosis in the Multi-Ethnic Sarcoidosis Consortium for Genetic Studies (MESARGEN)”, Foundation for Sarcoidosis Research, Illinois, US (250,000 kr)
- 2019 - 2020 Project grant “Genomic markers of sarcoidosis – a systemic inflammatory disease”, Sigurd och Elsa Goljes Minne Foundation, Stockholm, Sweden (20,000 kr)
- 2018 - 2020 Project grant “Elucidating mechanisms of chronic inflammation in ocular sarcoidosis”, Karolinska Institutet Foundation, Stockholm, Sweden (100,000 kr)
- 2019 - 2020 Project grant “Genetic investigations on chronic inflammatory diseases, such as cardiac sarcoidosis, Lars Hiertas Minne Foundation, Stockholm, Sweden (60,000 kr)”
- 2018 - 2020 Project grant “The role of expression quantitative trait loci (eQTLs) in lung cells of patients with sarcoidosis”, Karolinska Institutet Foundation, Stockholm, Sweden (60,000 kr)
- 2018 - 2019 Project grant “Clinical biomarkers for sarcoidosis disease”, Eva and Oscar Ahréns Foundation, Stockholm, Sweden (60,000 kr)
- 2017 - 2020 Project grant “Molecular biomarkers of sarcoidosis using MESARGEN, a multi-ethnic population-based consortium”, Swedish Heart and Lung Foundation, Stockholm, Sweden (900,000 kr)
- 2017 - 2019 Project grant “Calcium levels and sarcoidosis, A Mendelian Randomization Study”, Lisa and Johan Grönbergs Foundation, Stockholm, Sweden (60,000 kr)