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Peter Jackson Director, Staff Scientist: Cell Regulation |
"I joined Genentech in 2005 as a Staff Scientist, after ten years as a faculty member at the Stanford University School of Medicine. In 2006, I was named Director of Cell Regulation. As Director of Cell Regulation, I help define the strategy for therapeutics in critical physiological pathways including cell growth and the cell cycle, and to discover, validate and develop targets in these pathways.
I began my scientific career in the physical sciences and was drawn to biophysics and molecular biology, and ultimately, cell biology, by the idea that we could reduce complex biological systems to their more understandable physical basis by understanding the fundamental interactions among macromolecules, especially proteins. Understanding the activity of an enzyme or a critical protein-protein interaction and figuring out where and when those activities occur in the cell provides us with a defined target for altering physiology. That understanding informs our experiments, but also underlies the basis for targeted therapeutics. Today, the tools of cell biology are being applied to more complex networks of cell-cell interactions in normal and diseased tissue. It's quite a challenge to have all the tools to build the connection from the basic biophysics and biochemistry of proteins to the cell and animal physiology with enough rigor to control molecular events in the organism.
At Stanford, I had the opportunity to explore critical hypotheses about cell physiology and biochemistry. I came to Genentech to extend my interests in basic biochemical and cellular processes into the discovery and development of small molecule therapeutics. I was drawn to Genentech by the opportunity to combine basic research with the full platform of critical technologies required to develop therapeutics. Having the tools to create novel enzyme inhibitors provides a powerful path to understanding human biology and to treating human disease. Within the next few years, I believe it will be possible to discover critical new disease pathways and define new pathways to the clinic."
Current Projects "My laboratory has worked on the biochemistry of the cell cycle, including DNA replication and mitosis. Much of our effort has gone toward understanding how proteolytic degradation by the ubiquitin proteasome system regulates the cell cycle. We have made key contributions to understanding how proteins that regulate the cell cycle, called cyclins, accumulate and are destroyed in vertebrate cells and in eggs. A central finding was our discovery of inhibitors of E3 ubiquitin ligases and their role in cell cycle control. We have identified several critical factors regulating cyclins and have linked their misregulation to cancer, proliferative disease and senescence. We continue to define important regulators in mitosis and in the ubiquitin pathway. Ongoing projects include further definition of ubiquitin pathways important for cancer and new targets associated with mitosis and the cytoskeleton. Further, we have explored how cyclin activity is regulated in animal cells by central G1 signaling events, including those linked to cytokinesis and endocytosis.
Our recent work has also focused on signaling through the primary cilium. The primary cilium is an organelle with critical roles in signaling in tissues including the retina, nervous system, kidney and sensory organs. The importance of the cilia in signaling was only recently appreciated, but this structure organizes a still unknown number of receptor systems. These pathways are genetically linked to important degenerative diseases including renal cystic disease, obesity, diabetes, retinopathies and cancer signaling. We have used proteomic approaches to define regulatory networks linked to proteins that are defective in human diseases called ciliopathies. We are looking for critical receptor classes linked to these diseases and evaluating the therapeutic opportunities presented by these receptors."
Collaborations "Within Genentech, we maintain critical collaborations with other groups to support our discovery and development projects. At each step in the drug development process — from target discovery, target validation, construction of assays and animal models, small molecule inhibitor screening, and medicinal chemistry leading to a drug candidate — we collaborate with specific teams dedicated to those technologies. My department also works with these teams to expand these technologies and assays and to provide new ways to optimize and accelerate the drug development process.
We have especially important collaborations with bioinformatics and proteomics, where we are building tools to focus our discovery efforts for in-depth analysis of the most likely targets. Integrating the analysis of protein motifs, known functional domains, expression patterns and high-content functional assays, we can move rapidly from identifying gene candidates to proteomic analysis of potential pathways, and then to testing target candidates. We also have an important collaboration with chemistry, exploring the possibilities for drugging new classes of enzymes.
Outside of Genentech, we maintain significant collaborations with other companies and academic groups to expand our capabilities for pushing new targets forward."
Inspiration/Vision "The diversity of technologies and biological information today provides incredible opportunity for systematic approaches to understand untapped, core biochemical pathways in disease processes. Important diseases, including cancer and diabetes, still hold major unexplained regulatory steps. My department is defining the best path to quickly discover the key enzymes in these unexplained steps and to create drugs that can safely reverse or slow the disease process. Genentech provides a unique environment to move quickly from new research ideas to the clinic."