Predicting the Health Risks Resulting from Changes in DNA methylation and Gene Expression

While our genetic code, encoded in DNA, can be helpful to understand health and disease risk, the complete picture is far more complicated. As a result, many researchers have turned to epigenetics, which is the study of the changes in DNA modifications and conformation, and how these affect gene expression. Dr. Matteo Pellegrini, of the University of California, Los Angeles, combines statistics, computer science, biology, and genetics to better understand epigenetics. Using sophisticated computational approaches, he is able to interpret genomic data and thus, develop large-scale models of transcriptional and epigenetic regulation. Dr. Pellegrini believes that with a more complete understanding of the relationship between epigenetics and disease, he and other researchers will be able to design applications that predict risk for diseases ranging from diabetes to cancer.

 

Dr. Pellegrini’s research has been both basic and translational; some of his lab’s projects are at an advanced stage with commercialization potential, while others are still at the data collection stage. The advantage of epigenetic profiling is that it can be readily determined from patient samples using the latest sequencing technology. As this technology has become more affordable and therefore, accessible, the quantity of data available to researchers has grown exponentially. Using this data, Dr. Pellegrini believes he and his team can build applications to determine the current state of patients’ health and also predict disease risk. Surprisingly, the use of epigenetic profiles to predict human disease risk is still relatively untapped. Dr. Pellegrini’s research is producing novel approaches to developing computational tools to make this a reality.

 

Current research includes:

  • Translational Work: Dr. Pellegrini works to translate basic science into clinical settings where epigenetics tests are used to decipher who is at risk for metabolic diseases. For example, one test is able to place patients into either high or low risk categories to predict who will develop diabetes. This test, could potentially be brought into the clinic to more accurately determine patient risk.

  • Basic Science: Dr. Pellegrini’s studies of epigenetics in both mice and animals could help to improve health outcomes for patients in the future. In fact, many of his mice studies have laid the groundwork for the approaches they have developed and are now applying to human studies.

Matteo Pellegrini is a biophysicist who has served on the UCLA Life Sciences Division faculty since he joined the Department of Molecular, Cell and Developmental Biology in 2005. Dr. Pellegrini earned his B.A. in Physics at Columbia University and his Ph.D. in Physics at Stanford. He was a postdoctoral fellow at UCLA, where he worked on computational biology. Following his postdoctoral studies, Dr. Pellegrini co-founded a start-up company and later worked for the pharmaceutical company Merck before returning to UCLA. His laboratory research centers on the development of novel computational approaches to analyze large-scale genomic data. The Pellegrini group was instrumental in the development of whole genome bisulfite sequencing to measure the methylation status of nearly every cytosine in the genome. His present focus is on data produced using the latest generation of high throughput sequencers. Today the Pellegrini group is developing suites of tools for the analysis of high throughput sequencing data such as methC-seq, RNA-seq, ChIP-seq and Chromatin Conformation Capture seq.

Dr. Pellegrini was motivated by the ability to apply quantitative approaches as a student learning about physical science and biology. This initially led him to study the dynamics of biomolecules, but eventually his work moved to the study of nucleotide sequences and the application of statistical approaches to extract information from DNA. Today, he continues to be inspired by the fact that his basic science could have applications in clinical settings worldwide.

Website: pellegrini.mcdb.ucla.edu