The nature of the lab is to encourage the formulation and then development/maturation of new ideas, and to be responsive to changing directions in science, biomedical research and clinical medicine. Therefore, there are a substantial number of large and small research and development efforts, which can be clustered into a few major focus areas. The hot projects are active projects currently ongoing in the lab. Completely new directions are often proposed and so our hot projects change from time to time, but because of our experience and investment, certain themes continue to dominate.

Historically, the lab began with most of its resources directed at robotics, high throughput methods, etc. It quickly became apparent that data management, organization and analysis were necessary for our Human Genome work. The lab has evolved, now with computational biology, bioinformatics and interpretive biology as its primary areas of effort. The nature of computational biology is such that the results need to be validated in the lab to validate application and practicality, so the environment continues to be both a wet and dry lab, occupied by multi-disciplinary personnel conducting cross-disciplinary research.

• DNA Repeats: Prediction, Genotypes, and Phenotypes – Since the inception of the laboratory to capitalize on the products of the human genome project, we have been developing computational techniques to identify and rank potential causative genomic variants which can therefore be searched for efficiently in a directed study. The goals are not only to computationally target polymorphisms, but also to use the global findings to understand their overall role in medicine, evolution, basic biological processes and especially the mechanisms by which they manifest themselves to produce a phenotype. Those genomic regions (SNPs or repeat DNA) identified computationally are then pursued in the lab and with collaborators to advance the understanding of cardiac disease, cancer and other diseases.

• Text Data Mining: Finding hidden knowledge and information – Several algorithms and code projects have been developed to exploit the information found within the biomedical literature to discover hidden knowledge and pose potential hypotheses or interpretations of data queries. A select few of these discoveries provide the basis for new pursuits in the wet lab. To date, this effort has produced eTBLAST, IRIDESCENT and ARGH which uniquely perform document similarity clustering/searching, biomedical object (diseases, genes, chemicals, etc.) relationship identification and acronym resolving, respectively. These codes form the basis of a new spin-out company, etexx Biopharmaceuticals.

• Drug Discovery: Data mining inspired drug re-purposing – Driven and inspired by our data mining code, IRIDESCENT, are projects to rapidly develop new uses from existing drugs. Potential new applications for the numerous compounds and drugs discussed in Medline have been identified, especially for underserved cardiac disease indications (cardiac hypertrophy, arterial fibrillation, myocardial infarction, etc.). We are proceeding to test these hypothesized new uses in models for the disease in the lab, and in close collaboration with experts in the field.

• Omic: Genomics to Proteomics – Anchored from our developments for the human genome project and monitoring the data it has created, have inspired the development of new hardware, software and methods for post-genomics, ultimately leading to advances in genetics, genomics, transcriptiomics, epigenomics and proteomics. This work has produced a number of technologies that are in wide use, either through access to computational tools that we supply via the World Wide Web, or through high-throughput systems we have invented, demonstrated and have made available. These devices include oligo synthesizers, custom array technologies and associated methods for genotyping, methylation profiling, genomic annotation, DNA/protein and protein/protein interactions, etc. Several bioinformatics codes have been produced and are available for integrated analysis and visualization of DNA or protein sequence, to produce computed reagents (oligo designs) for mammals and biodefense agents, and to design microarrays and analyze them. New methods have recently focused on expanding the functionality of microarrays, including the analysis of methylation and DNA packing and their role in epigenetic control and disease, microarray genomic references and identification of organisms from their genomic signatures using a universal microarray.

• Light Biology: Custom array synthesis to tissue engineering – We have developed a series of new biomedically-focused applications that involve optical devices, from hyperspectral imaging to many new applications for the Texas Instruments Digital Light Processor. Specific applications that have been completed or under development include an automated device that produces custom high feature number oligonucleotide and peptide/peptoid microarrays called DOC; a patterning device and associated chemistry for tissue engineering; a spectrum generator for dermatological and cancer studies; and a hyperspectral imaging microscope/array scanner. The DOC device, in particular, formed the basis of the company Light Biology, which was recently acquired by Nimblegen, now Roche.

• Holographic TV: Computed holograms and dynamic projection – By illuminating a Texas Instruments Digital Light Processor chip with coherent radiation, a laser, we have demonstrated that we can generate and project dynamic, full color holograms on our prototype instrument prototype instrument. Algorithms developed enable us to produce near real time holograms that are projected on demonstration systems that are converging on a 3D workstation. Applications span from heads up displays for aircraft, to video games, to visualization workstations, to advanced Television.