Simmer Lab Research Statement
My research interests focus on normal and pathological tooth development. My research training was in biochemistry and I have worked, mostly with Dr. Yamakoshi, to isolate and characterize enamel and dentin proteins from developing pig teeth. I expressed the first recombinant amelogenin protein (rM179) and developed a purification method back in 1991. This protein, and the pig version (rP172), is still used by many labs to study amelogenin in vitro along with native amelogenins that we still isolate from developing pig teeth. I am probably best known for using protein sequence data from a serine protease isolated from developing pig teeth to publish the first cDNA and genomic sequences of what is now known as KLK4. We also fabricated and characterized Klk4 null mice. I am the recognized world expert on this protease and wrote invited chapters on this enzyme in the most recent 2 versions of the Handbook of Proteolytic Enzymes and have twice been an invited to speak on KLK4 at the International Symposium on Kallikreins and Kallikrein-Related Peptidases. Besides the biochemistry of tooth development, I have always been excited about genetics and am course director and principle lecturer for DENT 539 on Tooth Development, Regeneration and Genetics. Oligodontia runs in my family. I work with Dr. Hu to characterize the disease-causing mutations in the families with inherited tooth defects that Dr. Hu recruits. We have identified over 40 disease-causing mutations and were the first to report that FAM83H and ITGB6 mutations cause enamel defects, and that FAM20A mutations cause Enamel Renal Syndrome. Over time I have come to appreciate the great benefits of studying normal tooth development in animals and the genetics of pathological tooth development in humans. I believe that the first step toward improved treatments and cures for inherited conditions is to identify the genes/mutations that cause the disease. Knowing that a gene/protein is critical for normal tooth development in lab animals strongly influences our ability to conclude that an observed mutation in a family with inherited tooth defects is the cause of their disease. There are very few labs, worldwide that combine expertise in tooth development with the genetics of human tooth defects. I feel we are in a unique position to make advances in these areas and encourage you to provide the support necessary to continue our work, which has averaged 10 peer-reviewed/year for the last decade and will continue to do so with continue support from the NIDCR/NIH.