Sailalitha Bollepalli's dissertation reveals the epigenetic signature of smoking and weight-loss

M.Sc. Sailalitha Bollepalli’s thesis entitled "Epigenetic Profiling of Obesity and Smoking” was examined on Friday, 27 March, with the permission of the Faculty of Medicine of the University of Helsinki.

Defending a dissertation is arguably a very stressful situation. The situation became even more stressful to M.Sc. Sailalitha Bollepalli, when COVID-19 virus outbreak forced her to defend her thesis remotely, with the opponent Tuuli Lappalainen and audience joining the online streaming. Still, she did not let these challenging circumstances to disturb her, and became the first FIMM PhD candidate to complete her dissertation defense entirely online.

In her thesis work, Sailalitha Bollepalli focused on elucidating the role of epigenetic and transcriptomic markers in obesity and smoking. Her main aim was to identify weight-loss and smoking-associated signals by integrating these different types of genome-wide omics datasets by various statistical approaches and bioinformatics tools.

The societal impact of this research topic is enormous, since obesity and smoking are the two most important preventable health problems in the world today. Both are governed by a combination of genetic, epigenetic and environmental factors and the epigenetic modifications can provide a mechanistic link between genetic and environmental factors.

Sailalitha graduated from the University of East Anglia, Norwich, UK, in 2011, with masters in computational biology. In 2013, she got a highly competitive Marie Curie ITN scholarship as part of the EpiTrain program and moved to Finland to start her PhD project with Dr. Miina Ollikainen and Prof. Jaakko Kaprio. Her thesis study was performed as part of Professor Jaakko Kaprio’s Finnish Twin Cohort project entity.

The thesis consists of three publications. In the first publication of the thesis, molecular profiling data from adipose tissue and clinical parameters were repeatedly assessed during a one-year weight loss intervention study. The results indicated a potential regulatory role of DNA methylation in weight loss -associated transcriptome profiles.

The other two sub-studies focused on smoking-related epigenetic and expression level changes. Sailalitha showed that smoking affects both the methylome and transcriptome of the adipose tissue. By evaluating the associations between smoking-associated signals and adiposity measures, she was also able to demonstrate the wide-spread impact of smoking on metabolic health risk.

The data on smoking-related DNA methylation profiles was also applied on methodological development. As part of the thesis work, Sailalitha developed a robust smoking status classifier and demonstrated its’ performance using three different test datasets. This open-source tool EpiSmokEr (Epigenetic Smoking status Estimator) showed good discriminative ability in identifying current and never smokers compared to two other existing approaches.

Integration of multiple layers of omics data is essential to uncover the mechanisms behind complex phenotypes like obesity and smoking, and to design effective and efficient treatments. Epigenetic variants hold a great promise and may emerge as vital biomarkers and drug targets, taking us a step closer to understanding inter-individual variability in disease and realizing personalized medicine.

Sailalitha Bollepalli

Sailalitha will continue working at Jaakko Kaprio’s research group until the end of May to finish her ongoing projects and to settle her next career move. She is actively looking for a post-doc position and excited to see where research takes her next!

M.Sc. Sailalitha Bollepalli’s thesis was examined on Friday, 27 March, with the permission of the Faculty of Medicine of the University of Helsinki. Assistant Professor Tuuli Lappalainen, Columbia University, New York, USA, served as the opponent and Professor Jaakko Kaprio as the custos. The thesis is also available in an electronic format.