Our health depends upon both our genes and our environmental exposure. The current revolution in genomics makes it possible not only to determine our entire DNA sequence but also to begin to understand how our specific genome sequence can inform our health. In addition, our Center has recently demonstrated that it is possible to measure tens of thousands of components in blood to obtain a clear picture of our molecular picture during healthy and disease states.
Cancer is a genetic disease. It starts with one unlucky cell that loses control over growth and division and evades the immune system; it continues with accumulation of mutations in the genome of its progeny that make them grow even faster; and it eventually reaches the point where it is detected by a physician. SCGPM researchers are devising new approaches to study genomic changes in cancers, to understand cancer origins and progression, and to determine which altered genes might be developed into drug targets.
The human brain has 100 billion neurons that govern how we think, feel, learn, and remember. Defects in the formation of these neurons during development can lead to mental retardation, and during aging or in diseases such as Alzheimer's, there is a decline in cognitive function, particularly memory. SCGPM scientists are identifying the molecular changes that occur in brain cells during development, aging, and diseases. Identifying these molecular changes will provide new avenues to ameliorate neurological diseases and to prevent age-dependent decline in cognitive function.
SCGPM scientists are investigating the genetic basis of Mendelian, oligogenic, and complex human cardiovascular diseases employing high-throughput sequencing of informative families and association-based whole genome scanning methodologies with large case-control cohorts. Causal genetic variation identified through these approaches is under investigation to elucidate the mechanistic basis for the disease associations.
Drug responses vary between individuals because of genetic variation. The goal of pharmacogenomics research is the prediction of which drugs are effective in which individuals, at individualized doses. Stanford is a center of pharmacogenomics research, led by faculty affiliated with the SCGPM.
Scientists of the SCGPM working on technology development for sequencing human genomes efficiently at low cost were the first to collaborate with clinicians to see what can be learned from an individual's genome sequence. Predicted drug responses and disease susceptibilities were uncovered, in a proof-of-principle study of how whole genome sequencing of individuals will be used for patients' benefits in the future.
Sequencing of Geneticists
The SCGPM is currently engaged in a program to determine the whole genome sequences of several genetics experts who will be proof-of-principle 'patients' with the background to understand their genomes, and with the training to understand the ethical implications.
Gene Regulation and Genome Function
Every cell has the same DNA, but different types of cells do different things with that DNA. Blood cells make hemoglobin or immune proteins, brain cells make channels that conduct electricity, and liver cell make enzymes that break down toxins. Genomicists at the SCGPM conduct transformative studies on gene regulatory function to understand the molecular mechanisms of how DNA is differentially deployed, and how to intervene when these processes go awry in diseases such as cancer.
Human Variation and Population Genomics
Genetic variation is one big reason why we are different from one another. SCGPM scientists are at the forefront of studying how variation differs between individuals and ethnic groups, and how this knowledge can be used in medicine.
Comparing the genomes of different organisms allow inference of which genes and gene regulatory elements are important for basic biology to have been maintained over the course of evolution. Similarly, finding genes that are present in human but absent from its closest mammalian and primate relatives helps SCGPM scientists uncover what makes us human.
Model Organism Genomics
Fundamental mechanisms of cell and organismal biology are often studied in model organisms. Many SCGPM scientists use the most powerful model organisms such as the mouse or the fruit fly (and even yeast!) to study how genomes function and how gene regulation specifies which cells perform which functions in the organism.