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Research in the Center for Personalized Diagnostics

The successful future of medicine will depend on ensuring that patients are managed with treatments that are appropriate for each individual, a concept referred to as personalized medicine.  In the 18th century a physician’s diagnosis was often a restatement of the symptom, for example a patient was diagnosed with “the colic” or “the diarrhea.”  Advances in medicine in the 20th century led us to recognize that there were underlying causes that resulted in the same symptoms.  Diarrhea could be caused by an autoimmune phenomenon, like inflammatory bowel disease, or it could be due to an infection like cholera or shigella.  Treatments, which are best directed at the cause, would obviously be quite different for autoimmune disease and infection.  Now, in the 21st century, molecular medicine is teaching us that what we thought of as single diseases only a few years ago comprise many different molecular variants.  What was once simply breast cancer is now recognized to be more than a half dozen different diseases.  Each responds differently to a given therapy and carries a different prognosis.

To best manage patients, personalized medicine rests on two broad and equally important pillars.  First, it relies on novel therapeutics that are tailored to treat the specific molecular causes of each individual disease.  Academic and pharmaceutical company laboratories are working hard at defining these individual pathways.  Second, diagnostic tests are needed to quickly identify the specific disease an individual has and which treatment would be most appropriate.  The two approaches are mutually dependent.  A specific therapy only makes sense if there is a test to tell patients if they will benefit from it.

Broadly, our laboratory is interested in using a multidisciplinary approach to discovering new tools that will help advance the cause of personalized medicine . The completion of the human genome project signaled the start of a dramatic acceleration in the pace of biological research. With the application of large scale and high-throughput approaches, biology embraced a new era of technology development and information collection. One of the most compelling next steps has been learning the functional roles for all proteins. We base our work in the high throughput study of proteins, a next generation field called proteomics.  Proteins provide the verbs to biology; they are its engines and its bricks and mortar.  Most human disease is the result of protein dysfunction and nearly all drugs either act through proteins or are themselves proteins.

We initiated a project to create a sequence-verified collection of full-length cDNAs representing all coding regions for the human and several model organisms in a vector system that is protein expression-ready. By using a recombination-based vector system, users are able to execute the automated transfer of thousands of genes into any protein expression vector overnight. This repository, called the FLEXGene Repository (for Full-Length Expression-ready), enables the high-throughput screening of protein function for the entire set (or any customized subset) of human genes using any method of in vitro or in vivo expression. Our FLEXGene Repository has been built using an “open source” technology and is available to all biologists through the DNASU Plasmid Repository.  Our projects engage a wide range of tools from molecular biology, biochemistry, software engineering, informatics, medicine, chemical engineering, cell biology, database development and robotics in order to understand the functions of proteins and how they dysfunction in disease. Our strategy promises not only to improve therapeutic care by ensuring that patients are treated with right medicine for them, but also to greatly reduce the unnecessary side effects, the cost and the lost time of treating patients with therapies that are unlikely to be successful.