Genome Technology
The first is genome technology development with a particular focus upon approaches that will more rapidly elucidate the molecular genetic basis for human diseases. Under this heading lies our development of new methods for selectively isolating and resequencing large genomic regions. See our recent protocol in Nature Methods (PDF file) for more on this.
We are also interested in using balanced chromosomal rearrangements to rapidly identify candidate genes for complex human diseases. See our recent paper on idiopathic scoliosis (PDF file).
Also included under genomic technologies are our comprehensive transcription factor oligonucleotide microarrays for gene expression profiling. These arrays can be used in many diverse species (such as avians and mammals). See our recent paper in Genome Research for more on this (PDF file) .
We have also developed a set of cDNA amplification and cloning technologies for very small tissue samples (for example those derived by laser capture microdissection). We have applied these in the development of numerous cDNA libraries for the COGENE project (more on this below) and for the stem cell genome anatomy project (SCGAP). For more details on the SCGAP (funded by a grant from the National Institute of Diabetes and Digestive and Kidney Disease [NIDDK]), please visit the Wash. U. gut stem cell GAP web site at http://genome.wustl.edu/GSCGAP or the stem cell GAP site at http://www.scgap.org. We have also employed these methods in our various inner ear gene expression projects (see below).
The Inner Ear
Our second area of interest revolves around two very active projects that are focused upon the genetic circuitry of inner ear development and dysfunction. The long term goal of this research is to provide insights that will be useful in the ongoing search for cures for hearing loss. If you would like more information on the on the incidence of deafness and/or balance disorders, and what is being done to research their causes, please look at the following links:
If you would like background information on the developmental genetics of auditory hair cells then please see our recent review article (PDF file).
One of our projects is supported by a grant from the National Organization for Hearing Research Foundation. This is a collaborative effort between three groups of investigators at Washington University Medical Center. Dr. Lovett's group in the Department of Genetics, Dr. Warchol's group in the Department of Otolaryngology and Dr. Nancy Saccone's group in the Department of Genetics. This project deals with the regeneration of inner ear hair cells in birds and, more specifically, the pathways of gene expression that occur as birds regenerate their sensory epithelia. This is particularly important because mammals cannot regenerate these cell types and this is a major cause of human deafness. If you would like some background material on auditory hair cell regeneration click here. Also see our first report on gene expression profiles in the avian cochlea and utricle here (Hawkins et al., PDF). For access to our chicken gene expression profiles please click here.
Our other major interest in inner ear biology deals with gene expression profiling various developmental stages of the embryonic mouse inner ear. This is funded by a grant from the National Institute of Deafness and other Communications Disorders entitled "Gene Expression Profiling of the Developing Inner Ear" (5R01DC5632-3). Initially we are deriving these profiles from stages E9 through E15 at half day intervals and hybridizing these samples to Affymetrix GeneChips. We are also profiling various mouse knockout strains that affect inner ear development. For access to our mouse inner ear gene expression profiles click here.
Craniofacial Genetics
Our third area of interest is craniofacial genetics. Under funding from the National Institute of Dental and Craniofacial Research (NIDCR) we have derived the largest gene expression dataset yet of human craniofacial development. A description of this project and access to these data can be found here . Also funded by NIDCR is our collaborative project with Dr. Jeffrey Murray and other co-investigators based at the University of Iowa. We are employing bioinformatics, biostatistical and RNA interference approaches to detecting and analyzing important pathways in craniofacial development and exploring their relevance in craniofacial disorders.
Our policy on data release
Our aim is to make all of our expression profile data publicly accessible via the world wide web. We try to accomplish this in a timely fashion, but we do not post data that has not been replicated and at least partially analyzed. If you use information from our site we ask that you acknowledge its source and that these data were acquired under the auspices of the relevant funding source (e.g. the National Organization for Hearing Research Foundation).