Applying Computational Tools to Cure Cancer
Dr. Yotam Drier, from the Lautenberg Center for Immunology and Cancer Research at the Hebrew University, has set out to cure cancer. Using sophisticated experimental and computational methods, he is able to decipher the complex mechanisms that regulate the activity of thousands of genes and show how these mechanisms go awry in cancer.
Cancer: The Evasive Killer
Cancer is the number one killer in western society, and has proven a formidable disease to combat. One reason is that cancer cells are constantly changing (mutating) while also multiplying, acquiring new abilities and evading therapies. How do cancer cells do this? The key lies in mis-regulation of their genes.
Cancer occurs when one of the trillions of cells in our body begins multiplying uncontrollably, giving rise to a tumor mass. This may be caused by over-activity or under-activity of certain genes. For example, a gene meant to block cell growth may become inactive or a gene that suppresses the immune system may become excessively expressed, helping the tumor avoid our immune defense.
Yet perfectly healthy genes can still drive cancer. How? The answer lies in the regulatory DNA, the “other” 97% of our DNA that does not contain genes. These regulatory elements dictate how much of each gene will be present in every cell. However, the process is complex; science often still doesn’t know which regulatory elements are active and which genes they regulate, and especially not how these processes are disrupted in cancer.
At the Cutting-Edge of Cancer Research
Using advanced tools for genomic analysis and novel computational algorithms, Dr. Drier’s work has revealed several ways in which regulatory elements drive different cancers:
Genetic translocations: In cancer, parts of DNA can move, affecting DNA integrity. The movement of regulatory elements can change which genes are regulated, while also promoting the expression of genes that drive cancer.
Epigenetic changes: Chemical “markings” upon the regulatory DNA affect how the genes are regulated. In cancer cells, changes to these marks can affect the regulatory elements or the identity of the genes that they regulate.
3D genetic “tangles”: Each cell contains a sort of “tangled” DNA pom-pom, in which genes and their regulatory elements are in close proximity and interact. This structure is often changed in cancer cells. Without proper interactions, genes are not properly regulated, which in certain cases can drive cancer.
I’m aiming to systematically uncover the code of regulatory DNA and its disruption in cancer. This will allow us to both better understand how basic processes are regulated by, and encoded in, the DNA, as well as to uncover what drives various tumors we do not yet understand. We can suggest better strategies to manage these diseases and new drugs for targeting them.
At the Frontier of Computational Medicine
Dr. Drier’s lab team applies cutting-edge experimental techniques to studying and characterizing tumors in high throughput. In other words, rather than studying a specific gene or type of cancer, he studies a system: the entire cancer genome. Dr. Drier’s lab generates and analyzes a significant amount of data, including the tumor’s genetics, epigenetics, structure, gene expression, and more.
By applying powerful algorithms, Dr. Drier integrates his findings with other databases and develops computational models capable of predicting cancer-driving events, focusing on changes to regulatory DNA elements. Such events may include changes and differences among healthy and cancerous cells and what causes the cancer to appear, keep growing, and metastasize. In other words, Dr. Drier is capable of predicting the function of observed changes to regulatory DNA and their role in driving cancer.
Dr. Drier is currently taking a very broad approach; after identifying specific regulatory DNA alterations responsible for causing a particular form of cancer, his team will experimentally check whether indeed introducing these changes to cells causes the predicted outcome in order to establish cause and effect between regulatory DNA changes and cancer (rather than mere correlations).
Dr. Drier’s work is at the forefront of computational medicine, both at the Hebrew University and globally. His work has greatly contributed to our understanding of how disruptions to regulatory DNA can lead to cancer, and his breakthroughs are illuminating new ways to treat cancer patients.
I am very grateful for the opportunity to work in the diverse and stimulating environment that the Hebrew University’s Faculty of Medicine provides, where collaborations naturally form between physicians, experimental biologists, and computational biologists, an intersection that provides for very rewarding science.