A Bioinformatics Approach to Clinical Sequencing (Lecture)

Dr. Rhodes has a 12-year track record in cancer genomics and bioinformatics, with a significant focus on building systems to enable cutting-edge cancer research. He founded a successful cancer genomics and informatics company, Compendia Bioscience, recently acquired by Life Technologies. To build Compendia, he recruited and trained a talented team of 30 clinical scientists, bioinformaticists, cancer biologists, data curators and software engineers. As a graduate student, he led the development of Oncomine (Rhodes et al, PNAS, 2004; Rhodes et al, Nature Genetics, 2005), a cancer microarray database and data-mining application. Through the use of Oncomine, he contributed to several important discoveries, including the discovery of gene fusions in prostate cancer (Tomlins, Rhodes, et al., Science, 2005), SPINK1 in prostate cancer (Tomlins, Rhodes et al, Cancer Cell, 2008) and AGTR1 in breast cancer (Rhodes et al, PNAS, 2009). Compendia has since extensively expanded the Oncomine platform, and Oncomine is now widely recognized in academia and pharma as the leading cancer genomics data mining resource, with several hundred citations, and 15,000+ users. As Head of Medical Science Informatics at Life Technologies, he has turned his focus to next-generation sequencing data analysis, and leads several collaborations with pharmaceutical companies aimed at discovering novel oncogenic mutations and gene fusions from thousands of exomes and transcriptomes from The Cancer Genome Atlas. In his role as an Adjunct Assistant Professor at the U. of Michigan, he contributes to cancer genome analyses of prostate cancers (Grasso et al, Nature, 2012) and participates in and advises the clinical sequencing initiative MI-ONCOSEQ. (Ref:Bioconference)

Slides

Human Embryonic Stem Cells In Cancer Research

James Alexander Thomson is an American developmental biologist who is best known for deriving the first human embryonic stem cell line. He serves as director of regenerative biology at the Morgridge Institute for Research in Madison, Wisconsin, and is a professor at the University of Wisconsin School of Medicine and Public Health.He is one of the leading scientific innovators in stem cell research.

In this lecture he explores current understanding how human embryonic cells can form any cell in the body and the implications for cancer research.

New Lessons in Cancer Research

Cancer is a conniving enemy. Try to kill it off through surgery or chemotherapy, and it finds a way to sneak back in. Jacqueline Lees tells an engaged Soap Box audience what insights and tools research now offers in the longstanding battle against this relentless disease.

Big gains have come from molecular study of tumors at different stages, Lees says. It often takes many years for a cancerous cell to develop into a dangerous tumor, one that can yield metastases. There might be six phases of development over 15 years in a cancer’s evolution, and scientists have formed a good understanding of what these different lesions look like in various cancers, and how they behave. Lees calls this process “actually a beautiful example of evolution,” since the cell that mutates and begins to divide uncontrollably evolves to become more successful relative to other cells in the tissue.

 

Other research focuses on the genetic basis of cancers. Two “flavors” of genes appear responsible for provoking cancerous changes in cells: oncogenes and tumor suppressor genes. It may be possible to intervene along the genetic pathways underlying cancer growth, says Lees. Her own work, involving mutant mice and zebrafish, hopes to identify the mechanisms involved in specific kinds of tumors, and to figure out ways of inhibiting cancer cell growth. Understanding the nature of specific cancers might help prevent treating people with chemical agents that don’t work for their kind of cancer, and that actually increase their tumor’s growth.

With the advent of fast and inexpensive genetic screens, it may soon be possible to determine whether each of us carries genes that predispose us toward certain kinds of cancers. But Lees questions the universal adoption of DNA testing, not just because of privacy concerns, but because there may very well be no known cure if a predisposition to disease is found. “If we sequenced every baby, and said you’re highly predisposed to a cancer, and there’s nothing we can do, would that be information people want to have?” Lees wonders. “If we could find a rapid way to sequence small subsets of genome, identify people with high risk and we could treat them if we knew they had those diseases, there’d be an argument for that, much as we do testing for diseases where we know can intervene if find children carrying them,” says Lees.

About the Speaker

Jacqueline Lees SM '86, PhD '90

Associate Director
MIT Center for Cancer Research;
Professor of Biology

Jacqueline Lees' research is focused on identifying the proteins and pathways that play a key role in tumorigenicity and establishing the mechanism of their action in both normal and tumor cells. Her lab uses a combination of molecular and cellular analyses, mutant mouse models and genetic screens in zebrafish.

Lees received her Ph.D. in 1990 from the University of London.

Cancer Research in the Genomic Era

Eric Lander likens the current age of biological discovery to the days of great ocean-going exploration. After the world was mapped, no one could imagine what it was like to live “before you knew what would happen if you sailed west.” Following the current revolution in biology, we “won’t be able to imagine what science was like...” This transformation, claims Lander, will be complete in the next decade or so. “MIT students in 2020 will look back with a mixture of amusement and horror at the late 20th century and say, ‘Imagine, people spent years looking for the gene for something.’”

Lander views biology as a vast library that will soon contain information not just about the DNA sequences of species, but ‘volumes’ on individuals, tissues, and cells. With great effort, researchers deciphered the secrets of chromosomes, the double helix, and more recently, the human genome and that of other species. But progress in such discoveries is now moving at a much faster clip due to high-speed computing and the Internet. MIT currently sequences ¼ million pieces of DNA per day, says Lander. He projects this pace will quicken by 20 fold in the next several years.

Fortified by this progress, Lander has compiled an ambitious ‘to-do list:’ identifying “everything that matters” in the human genome, from proteins to the things that control genes; knowing all human genetic variation in the population; knowing how to recognize when a cell “is thinking of one thing or another” based on how genes are turned on or off; knowing all the mechanisms that cause cancer and how to modulate all the genes.

Astonishingly, he says, “This is not the to-do list of the next century, but the next decade.” Lander is confident that researchers will in the not-distant future generate a catalog of the unique genetic signatures associated with “different flavors” of a type of cancer. Scientists will find patterns in diseases, genes and drug responses, and eventually assemble a list of all the genetic variants in the human genome that put individuals at risk for different diseases. These various gene databases will serve “as foundational information for biology for centuries to come,” concludes Lander.

About Speaker

Eric Lander was a world leader of the international Human Genome Project, the effort to map the blueprint for a human being. Today, Lander is using the knowledge of the human genome to tackle the fundamental issue of medicine: to find the causes of disease.

Lander received his Ph.D. in mathematics from Oxford in 1981, as a Rhodes Scholar. He joined Whitehead Institute in 1986 and founded the Whitehead Institute/MIT Center for Genome Research in 1990. Lander became the founding director of the newly created Broad Institute in 2003.

Lander is a member of the U.S. National Academy of Sciences, and U.S. Institute of Medicine. He was a MacArthur Fellow (1987-1992), and earned the Woodrow Wilson Prize from Princeton University(1998); the Baker Memorial Award for Undergraduate Teaching at MIT (1992); the City of Medicine Prize (2001); and the Gairdner International Prize (2002).