A. PERSONAL STATEMENT
My transition from neuroscientist to oral biologist has been a circuitous but very rewarding journey. Upon joining Creighton’s 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 initiated primary human oral fibroblast studies with lysophosphatidic acid [(LPA), a lipid mediator which I had worked with during my studies in the lung system at the University of Nebraska Medical Center, Department of Pharmacology. 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 twenty years that I have been teaching/research faculty in the Dental School, I have served as the P.I. of the seminal studies that have established the essential role of 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. Our 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 LPA’s role in inflammatory periodontal disease using an established mouse model of this disease.

B. OTHER EXPERIENCE AND PROFESSIONAL MEMBERSHIPS
1988-1989: Post-doctoral Fellowship, Department of Microbiology Training Grant, DHHS 1T32 A107276- 02, University of Missouri-Columbia
1991-1993: Recipient, Individual NRSA Training Grant, Cerutis/DHHS/NIH/NIMH MH10060-02, Department of Pharmacology, University of Nebraska Medical Center

C. HONORS
2002: Nominated for the Dr. Ted Urban Award for Excellence in Pre-Clinical Education by the Dental Class of 2002 2005: Invited speaker, first NIH/NIDCR-Industry Meeting: Pathway to Product Development, Nov 7-8, Bethesda, MD.
2008: Invited reviewer, SBIR/STTR proposals ZRG1 MOSS-E (11) B meeting, April 24
2012: Invited reviewer, R15 (AREA) proposals 2012/10 ZRG1 MOSS-T (91) S meeting, June 12 C.

D. CONTRIBUTION to SCIENCE
1. Human Oral Fibroblast Physiology: Since 1999, 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.
a. Cerutis DR, Dreyer A, Cordini F, McVaney 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. 2004 Feb;75(2):297-305.PMID:15068119.
b. Cerutis DR, Dreyer AC, Vierra MJ, King JP, Wagner DJ, Fimple JL, Cordini F, McVaney 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. 2007 Jun;78(6):1136-45.PMID:17539729.

2. LPA Receptor Subtype Regulation of Oral Fibroblast Physiology: I then used the data from the papers above to submit an R15 application to the NIH/NIDCR 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. 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, McVaney 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. 2009 Aug;80(8):1338-47. PMID:19656035.
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.
a. Cerutis DR, Headen KV, Perry G, Parrish LC, McVaney TP, Jordan CS. Lysophosphatidic acid (LPA) receptor subtypes on human gingival and periodontal ligament fibroblasts are regulated by PDGF. FASEB J. 2010 April 24:769.11. DOI: 10.1096/fj.1530-6860 3.

3. Analytical Saliva Studies: To investigate the association of LPA with periodontal disease, we developed a sensitive LC-MS/MS method to analyze LPA species in saliva and gingival crevicular fluid (GCF). We found the LPA species unchanged in ratios, but a 10-fold, pharmacologically significant elevation in moderate-severe periodontal disease. This method remains one of the most sensitive published to date for LC-MS/MS analysis of LPA species in saliva and GCF.
a. Bathena SP, Huang J, Nunn ME, Miyamoto T, Parrish LC, Lang MS, McVaney TP, Toews ML, Cerutis DR, Alnouti Y.Quantitative determination of lysophosphatidic acids (LPAs) in human saliva and gingival crevicular fluid (GCF) by LC-MS/MS. J Pharm Biomed Anal. 2011 Sep 10;56(2):402-7. PMID:21703797

4. Gene regulation by LPA: As LPA controlled such critical aspects of oral fibroblast biology, we did a pilot microarray study with LPA-stimulated GF. 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.
a. Cerutis DR, Weston MD, Ogunleye AO, McVaney TP, MiyamotoT. Lysophosphatidic acid (LPA) 18:1 transcriptional regulation of primary human gingival fibroblasts. Genomics Data December 2014 2:375-377. doi:10.1016/j.gdata.2014.10.014
b. Cerutis DR, Weston MD, Alnouti Y, Bathena SP, Nunn ME, Ogunleye AO, McVaney TP, Headen KV, Miyamoto T. A Major Human Oral Lysophosphatidic Acid Species, LPA 18:1, Regulates Novel Genes in Human Gingival Fibroblasts. J Periodontol. 2015 May;86(5):713-25. PMID:25660500

5. 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. The results of our seminal body of work now suggest that LPA likely modulates oral fibroblast inflammatory responses and their interactions with neutrophil / lymphocyte chemotactic and immune events in the periodontium. Ultimately, LPA may participate in regulating inflammation in periodontal disease, where the balance of destruction of gingival tissue, periodontal ligament, and alveolar bone in response to periodontal pathogens determines disease status and progression. Taken together, LPA merits further investigation of its regulatory role in the oral system; we continue these investigations.

E. COMPLETE LIST of PEER-REVIEWED ARTCLES
For Complete List of Published Scientific Research Work see  MyBibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/1bALDgsXdjUkp/bibliography/47934055/public/?sort=date&direction=ascending.

1. Cerutis DR, Headen KV, Ogunleye AO, Williams DE. A High-resolution Immunohistochemical Method for Studying Receptor Expression on the Periodontal Ligament of Whole-mount Human Tooth Roots. International Journal of Experimental Dental Science  2016; 5(2):99-103. http://www.ijeds.com/Ahead_of_Print.aspx   
2. A Major Human Oral Lysophosphatidic Acid Species, LPA 18:1, Regulates Novel Genes in Human Gingival Fibroblasts. Cerutis DR, Weston MD, Alnouti Y, Bathena SP, Nunn ME, Ogunleye AO, McVaney TP, Headen KV, Miyamoto T. J Periodontol. 2015 May;86(5):713-25. doi: 10.1902/jop.2015.140592. Epub 2015 Feb 9. PMID:25660500
3. Lysophosphatidic acid (LPA) 18:1 transcriptional regulation of primary human gingival fibroblasts.Cerutis DR, Weston MD, Ogunleye AO, McVaney TP, Miyamoto T. Genom Data. 2014 Oct 23;2:375-7. doi: 10.1016/j.gdata.2014.10.014. eCollection 2014 Dec. PMID:26484133 Free PMC Article
4. Maresin-1 reduces the pro-inflammatory response of bronchial epithelial cells to organic dust.Nordgren TM, Heires AJ, Wyatt TA, Poole JA, LeVan TD, Cerutis DR, Romberger DJ. Respir Res. 2013 May 10;14:51. doi: 10.1186/1465-9921-14-51.PMID:23663457Free PMC Article
5.Quantitative determination of lysophosphatidic acids (LPAs) in human saliva and gingival crevicular fluid (GCF) by LC-MS/MS.Bathena SP, Huang J, Nunn ME, Miyamoto T, Parrish LC, Lang MS, McVaney TP, Toews ML, Cerutis DR, Alnouti Y. J Pharm Biomed Anal. 2011 Sep 10;56(2):402-7. doi: 10.1016/j.jpba.2011.05.041. Epub 2011 Jun 6.PMID: 2170379 Free PMC Article
6.Non-bioabsorbable vs. bioabsorbable membrane: assessment of their clinical efficacy in guided tissue regeneration technique. A systematic review. Parrish LC, Miyamoto T, Fong N, Mattson JS, Cerutis DR. J Oral Sci. 2009 Sep;51(3):383-400. Review.PMID:19776505 Free Article
7.Lysophosphatidic Acid signals through specific lysophosphatidic Acid receptor subtypes to control key regenerative responses of human gingival and periodontal ligament fibroblasts. George J, Headen KV, Ogunleye AO, Perry GA, Wilwerding TM, Parrish LC, McVaney TP, Mattson JS, Cerutis DR. J Periodontol. 2009 Aug;80(8):1338-47. doi: 10.1902/jop.2009.080624. PMID:19656035
8. Sphingosine 1-phosphate potentiates human lung fibroblast chemotaxis through the S1P2 receptor.Hashimoto M, Wang X, Mao L, Kobayashi T, Kawasaki S, Mori N, Toews ML, Kim HJ, Cerutis DR, Liu X, Rennard SI. Am J Respir Cell Mol Biol. 2008 Sep;39(3):356-63. doi: 10.1165/rcmb.2006-0427OC. Epub 2008 Mar 26.PMID:18367729Free PMC Article
9.Lysophosphatidic acid modulates the healing responses of human periodontal ligament fibroblasts and enhances the actions of platelet-derived growth factor. Cerutis DR, Dreyer AC, Vierra MJ, King JP, Wagner DJ, Fimple JL, Cordini F, McVaney TP, Parrish LC, Wilwerding TM, Mattson JS. J Periodontol. 2007 Jun;78(6):1136-45.PMID:17539729
10.Lysophosphatidic acid modulates the regenerative responses of human gingival fibroblasts and enhances the actions of platelet-derived growth factor.Cerutis DR, Dreyer A, Cordini F, McVaney TP, Mattson JS, Parrish LC, Romito L, Huebner GR, Jabro M.J Periodontol. 2004 Feb;75(2):297-305. Erratum in: J Periodontol. 2004 Oct;75(10):1437-8.PMID: 15068119
11.Complications associated with diabetes mellitus after guided tissue regeneration--a case report revisited.Mattson JS, Cerutis DR, Parrish LC.Compend Contin Educ Dent. 2002 Dec;23(12):1135-8, 1140, 1142 passim; quiz 1146.PMID:12592715
12.Osteoporosis: a review and its dental implications.Mattson JS, Cerutis DR, Parrish LC. Compend Contin Educ Dent. 2002 Nov;23(11):1001-4, 1006, 1008 passim; quiz 1014. Review.PMID: 12526189
13.Diabetes mellitus: a review of the literature and dental implications.Mattson JS, Cerutis DR.Compend Contin Educ Dent. 2001 Sep;22(9):757-60, 762, 764 passim; quiz 773. Review. PMID:11692399
14.Lysophosphatidic acid and EGF stimulate mitogenesis in human airway smooth muscle cells.Cerutis DR, Nogami M, Anderson JL, Churchill JD, Romberger DJ, Rennard SI, Toews ML.Am J Physiol. 1997 Jul;273(1 Pt 1):L10-5.PMID:9252534
15.Neurotrophins and their receptors in nerve injury and repair.Ebadi M, Bashir RM, Heidrick ML, Hamada FM, Refaey HE, Hamed A, Helal G, Baxi MD, Cerutis DR, Lassi NK.Neurochem Int. 1997 Apr-May;30(4-5):347-74. Review.PMID:9106250
16.Buffers differentially alter the binding of [3H]rauwolscine and [3H]RX821002 to the alpha-2 adrenergic receptor subtypes.Deupree JD, Hinton KA, Cerutis DR, Bylund DB. J Pharmacol Exp Ther. 1996 Sep;278(3):1215-27.PMID:8819505
17.Regulation of hamster alpha 1B-adrenoceptors expressed in Chinese hamster ovary cells. Zhu SJ, Cerutis DR, Anderson JL, Toews ML.Eur J Pharmacol. 1996 Mar 28;299(1-3):205-12. PMID:8901024
18.6-Hydroxydopamine-mediated induction of rat brain metallothionein I mRNA. Rojas P, Cerutis DR, Happe HK, Murrin LC, Hao R, Pfeiffer RF, Ebadi M.Neurotoxicology. 1996 Summer;17(2):323-34.PMID:8856728 19.Expression and regulation of brain metallothionein.Ebadi M, Iversen PL, Hao R, Cerutis DR, Rojas P, Happe HK, Murrin LC, Pfeiffer RF.Neurochem Int. 1995 Jul;27(1):1-22. Review. PMID:7655341
20.Distribution of zinc metallothionein I mRNA in rat brain using in situ hybridization. Hao R, Cerutis DR, Blaxall HS, Rodriguez-Sierra JF, Pfeiffer RF, Ebadi M. Neurochem Res. 1994 Jun;19(6):761-7.PMID:8065534
21.Cloning and expression of the alpha 2C-adrenergic receptor from the OK cell line. Blaxall HS, Cerutis DR, Hass NA, Iversen LJ, Bylund DB.Mol Pharmacol. 1994 Feb;45(2):176-81.PMID: 7509437

F. OTHER PUBLICATIONS:
1. Oxley KS, Jackson JB, D.R. Cerutis. Reference Module in Biomedical Sciences, 2015: Acne (Vulgaris and Rosacea) http://dx.doi.org/10.1016/B978-0-12-801238-3.04820-0.
2. Johnson M, Cerutis DR. Reference Module in Biomedical Sciences, 2015: Osteoporosis. http://dx.doi.org/10.1016/B978-0-12-801238-3.05196-5
3. Al-Hashimi I, Cerutis DR. Reference Module in Biomedical Sciences, 2014: Sjögren's Syndrome. http://dx.doi.org/10.1016/B978-0-12-801238-3.05302-2
4. Cerutis DR. Reference Module in Biomedical Sciences, 2014: Measles. http://dx.doi.org/10.1016/B978-0-12-801238-3.05135-7
5. Cerutis DR. Reference Module in Biomedical Sciences, 2014: German Measles (Rubella) http://dx.doi.org/10.1016/B978-0-12-801238-3.05037-6
6. Cerutis DR. Reference Module in Biomedical Sciences, 2014: Systemic Lupus Erythematosus. http://dx.doi.org/10.1016/B978-0-12-801238-3.05336-8

PUBLISHED ABSTRACTS (only shown:since 2010)

1.Cerutis DR, Weston MD, Nunn ME, Williams DE, Ogunleye AO, Miyamoto T. Lysophosphatidic Acid Regulates the Vitamin D Receptor and its Metabolism-Related Genes in Human Gingival Fibroblasts. FASEB J 32, April 2018:lb562.
2. Cerutis DR, Nichols MG, Khan SA*, Miyamoto T. Localization of the Platelet-Activating Factor Receptor on the Intact Human Periodontal Ligament. FASEB J April 2017, 31:lb24
3. Cerutis DR, Fischer NG*, Gnabasik R*, Lang MS, Baruth A. The Role of Nanoscale Roughness on Cell Attachment Following Titanium-based Instrumentation of Titanium, Titanium-Zirconium, and Zirconia Surfaces
FASEB J April 2016 30:1034.7
4. Cerutis DR, Nichols M, Hironaka M*, Miyamoto T, Khan S*, Ogunleye A, McVaney TP. Complementing Confocal Detection of Antibody-labeled Lysophosphatidic Acid Receptors in Human Gingivae with Label-free Second Harmonic Generation Confocal Microscopy Detection of Collagen. FASEB J April 2015 29:LB26
5. Cerutis DR, Nichols M, Jenzer A*, Khan S*, McVaney TP, Miyamoto T, Kaldahl W. Label-free imaging of the regenerating human periodontal ligament and gingival tissue using second harmonic generation confocal microscopy. FASEB J April 2014 28:LB41
6. Cerutis DR, Weston MD, Nunn ME, Ogunleye AO, McVaney TP, Headen KV, Miyamoto T. Lysophosphatidic acid regulates SPHK1 and GPR68/OGR1 in human gingival fibroblasts. FASEB J April 2013 27:lb569
7. Cerutis DR, Weston MD, Ogunleye A, McVaney TP, Headen KV, Parrish LC. Lysophosphatidic acid regulates a complex array of genes in human gingival fibroblasts. April 2011. FASEB J April 2011 25:539.1
8. Cerutis DR, Headen KV, Perry G, Parrish LC, McVaney TP, Curtis SJ*. Lysophosphatidic acid (LPA) receptor subtypes on human gingival and periodontal ligament fibroblasts are regulated by PDGF. April 2010. The FASEB Journal 24(1): Supplement 769.11
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Curriculum Vitae