Faculty Office of the President. A. PERSONAL STATEMENTI have transitioned from neuroscientist to oral biologist this has been a very rewarding, if circuitous, journey. Upon joining Creightons Dental School, I sought to mesh my background with the research interests and needs of the clinical departments, particularly Periodontics and Oral and Maxillofacial Surgery. In collaboration with the Chairs and faculty of both departments we started primary human oral fibroblast studies with lysophosphatidic acid LPA, which I had done my post doctoral studies with in the lung system at UNMC. At that time, LPA and its actions had never been described in the dental literature. Based on pilot studies, I hypothesized that it might be a candidate factor for periodontal regeneration. Over the eighteen years that I have been teachingresearch faculty in the Dental School, I have served as the P. Software Apha Standard Methods 22Nd Edition Hard' title='Software Apha Standard Methods 22Nd Edition Hard' />I. LPA in human oral fibroblast biology, and we have accumulated a large body of knowledge and expertise in wound healing and inflammation, particularly in the oral system. For our studies both NIH and foundation supported we have involved dental and undergraduate students, and collaborated with clinicians and researchers at Creighton, our Dental School, and at the University of Nebraska Medical Center. Software Jyotish on this page. Our recent discovery that LPA significantly and extensively regulates inflammatory transcripts in human oral fibroblasts and is very likely a pivotal regulatory mediator in human periodontal disease now opens the way for studying the role of LPA species and LPA receptor subtypes in the pathogenesis of periodontal disease. To this end, we will further the in vitro studies by proposing to determine LPAs role in inflammatory periodontal disease using an established mouse model of this disease. B. OTHER EXPERIENCE AND PROFESSIONAL MEMBERSHIPS1. Official website for Dr Sarah Wollaston, Conservative Member of Parliament for Totnes. International Journal of Engineering Research and Applications IJERA is an open access online peer reviewed international journal that publishes research. Software Apha Standard Methods 22Nd Edition Hard' title='Software Apha Standard Methods 22Nd Edition Hard' />Post doctoral Fellowship, Department of Microbiology Training Grant, DHHS 1. T3. 2 A1. 07. 27. University of Missouri Columbia. Recipient, Individual NRSA Training Grant, CerutisDHHSNIHNIMH MH1. Department of Pharmacology, University of Nebraska Medical Center. C. HONORS2. 00. 2 Nominated for the Dr. Software Apha Standard Methods 22Nd Edition Hard' title='Software Apha Standard Methods 22Nd Edition Hard' />Ted Urban Award for Excellence in Pre Clinical Education by the Dental Class of 2. Invited speaker, first NIHNIDCR Industry Meeting Pathway to Product Development, Nov 7 8, Bethesda, MD. Invited reviewer, SBIRSTTR proposals ZRG1 MOSS E 1. PresentationVRSeptember2016/Gimp.png' alt='Software Apha Standard Methods 22Nd Edition Hard' title='Software Apha Standard Methods 22Nd Edition Hard' />B meeting, April 2. Invited reviewer, R1. AREA proposals 2. ZRG1 MOSS T 9. 1 S meeting, June 1. C. D. CONTRIBUTION to SCIENCE1. Human Oral Fibroblast Physiology Since 1. I have engaged in collaborative research with dental clinical faculty in Periodontics and in Oral and Maxillofacial Surgery. Our foundational studies funded by the Health Futures Foundation showed that lysophosphatidic acid LPA controlled the healing responses of human oral fibroblasts. We found that LPA was a major regulatory factor for these cells, and published these seminal LPA papers in the dental literature they are now being referenced and used by other investigators to widen the investigation on the role of LPA in oral cell biology and periodontal disease. Cerutis DR, Dreyer A, Cordini F, Mc. Vaney TP, Mattson JS, Parrish LC, Romito L, Huebner GR, Jabro M. Lysophosphatidic acid modulates the regenerative responses of human gingival fibroblasts and enhances the actions of platelet derived growth factor. J Periodontol. 2. Feb 7. 52 2. 97 3. PMID 1. 50. 68. 11. AoIdFh8/Um0VxCdcOpI/AAAAAAAAHfU/2y_l0q7D_e4/s640/kr1.jpg' alt='Software Apha Standard Methods 22Nd Edition Hard' title='Software Apha Standard Methods 22Nd Edition Hard' />Cerutis DR, Dreyer AC, Vierra MJ, King JP, Wagner DJ, Fimple JL, Cordini F, Mc. Vaney TP, Parrish LC, Wilwerding TM, Mattson JS. Lysophosphatidic acid modulates the healing responses of human periodontal ligament fibroblasts and enhances the actions of platelet derived growth factor. J Periodontol. 2. Jun 7. 86 1. 13. PMID 1. LPA Receptor Subtype Regulation of Oral Fibroblast Physiology I then used the data from the papers above to submit an R1. NIHNIDCR which was funded on the initial round. LPA had only recently begun to be appreciated by the larger scientific community in other fields as a key regulatory molecule participating in a multitude of homeostatic and pathophysiological processes. Face Software Key. The study below established the pivotal role of the main human salivary LPA species in differentially regulating human oral fibroblast physiology a. George J, Headen KV, Ogunleye AO, Perry GA, Wilwerding TM, Parrish LC, Mc. Vaney TP, Mattson JS, Cerutis DR. Lysophosphatidic Acid signals through specific lysophosphatidic Acid receptor subtypes to control key regenerative responses of human gingival and periodontal ligament fibroblasts. J Periodontol. 2. Aug 8. 08 1. 33. PMID 1. With a small grant from Becton Dickinson, we used flow cytometry to profile LPA receptor subtype expression on oral fibroblasts from multiple donors, and showed that they express the first five LPA1 5 of the six LPARs cloned to date. The expression of so many LPAR subtypes supports our proposition that LPA plays an essential role in oral fibroblast biology. Cerutis DR, Headen KV, Perry G, Parrish LC, Mc. Vaney TP, Jordan CS. Lysophosphatidic acid LPA receptor subtypes on human gingival and periodontal ligament fibroblasts are regulated by PDGF. FASEB J. 2. 01. 0 April 2. DOI 1. 0. 1. 09. Analytical Saliva Studies To investigate the association of LPA with periodontal disease, we developed a sensitive LC MSMS method to analyze LPA species in saliva and gingival crevicular fluid GCF. We found the LPA species unchanged in ratios, but a 1. This method remains one of the most sensitive published to date for LC MSMS analysis of LPA species in saliva and GCF. Bathena SP, Huang J, Nunn ME, Miyamoto T, Parrish LC, Lang MS, Mc. Vaney TP, Toews ML, Cerutis DR, Alnouti Y. Quantitative determination of lysophosphatidic acids LPAs in human saliva and gingival crevicular fluid GCF by LC MSMS. J Pharm Biomed Anal. Sep 1. 0 5. 62 4. PMID 2. 17. 03. 79. Gene regulation by LPA As LPA controlled such critical aspects of oral fibroblast biology, we did a pilot microarray study with LPA stimulated GF. Crash Time 2 Mods'>Crash Time 2 Mods. Based on these data, we hypothesized that exposure to LPA would modulate GF expression of various categories of critical genes that orchestrate wound healing and inflammatory responses. Then, using GF from multiple donors, we showed extensive gene expression changes correlated with LPA treatment. The significantly changed genes and the derived biological networks we reported suggested major regulation of genes involved in orchestrating inflammatory type responses of oral fibroblasts to LPA. Cerutis DR, Weston MD, Ogunleye AO, Mc. Vaney TP, Miyamoto. T. Lysophosphatidic acid LPA 1. Genomics Data December 2. Cerutis DR, Weston MD, Alnouti Y, Bathena SP, Nunn ME, Ogunleye AO, Mc. Vaney TP, Headen KV, Miyamoto T. A Major Human Oral Lysophosphatidic Acid Species, LPA 1. Regulates Novel Genes in Human Gingival Fibroblasts. J Periodontol. 2. May 8. 65 7. 13 2. PMID 2. 56. 60. 50. Future Studies LPA is a highly conserved molecule with profound regulatory actions in health and disease. Except for my laboratory, LPA has received relatively little attention aimed at deciphering its role in oral homeostasis and periodontal disease. One of the two major sources of LPA is activated platelets, which are always present in the inflamed periodontium due to the tissue destruction and bleeding characteristic of moderate severe periodontal disease.