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Program Director/Principal Investigator (Last, First, Middle): BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Jan C-C. Hu Professor eRA COMMONS USER NAME JANCCHU EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION DEGREE (if applicable) YEAR(s) FIELD OF STUDY National Taiwan University, School of Dentistry BDS 1979-1985 Dentistry University of Southern California Certificate 1985-1988 Pediatric Dentistry University of Southern California PhD 1985-1990 Crainofacial Biology University of Southern California Post-doc 1991-1993 Craniofacial Mole. Biol. A. Personal Statement My primary research interest and experience focus on the formation of tooth enamel and dentin. Our laboratory has characterized the critical components of the developing tooth at the protein, cDNA and gene level from multiple species. Specifically, we were the first to characterize enamelin, kallikrein4 and MMP20 in developing teeth, which allowed us to establish knockout mouse models, which demonstrated enamel structural defects in the absence of specific genes. Subsequently, transgenic mouse models were generated to rescue the enamel defects in the knockout background. To achieve our research goals in understanding tooth development and regenerating tooth elements, optimized experimental protocols for conducting gene/protein arrays, molecular cloning, protein engineering, morphological and cell/organ culture experiments using developing teeth from mouse and pig have been established. In addition, specific constructs, DNA clones and antibodies have been generated and characterized to aid the research on tooth development and malformations. Our lab is one of the few research laboratories worldwide providing screening for families with selected, inherited dental defects (please see http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/director/Simmer?db=genetests&search_param=begins_ with). Our ultimate goal is to apply basic science discoveries toward devising therapeutic measures for human disorders involving tooth defects. My clinical research centers on pulp biology, I have established a multi-center, multi-operator, long-term, prospective study investigating the efficacy of mineral trioxide aggregate (MTA) in primary tooth pulpotomies. My clinical training and experiences have allowed my involvement in projects aiming at improving oral health among children. With 42-month study outcome analysis, it is demonstrated that clinically and radiographically, MTA is superior than that of the diluted formocresol, the current gold standard. Results of these studies may change how dentists perform pulpotomies, which is a procedure performed on millions of pulpally infected primary and young permanent teeth every year. In supporting the graduate education of our institution, I directed the Unit of Pediatric Dentistry from 2006 to 2008. Currently I am the director of the Oral Health Sciences PhD program. B. Positions and Honors Positions and Employment 1988-1991 Clinical Assistant Professor of Pediatric Dentistry, School of Dentistry, USC. 1990-1993 Clinical Associate, Pediatric Dentistry, Children's Hospital of Los Angeles 1993-1999 Assistant Professor, Department of Pediatric Dentistry, School of Dentistry, UTHSCSA. 1999-2002 Associate Professor, Department of Pediatric Dentistry, School of Dentistry, UTHSCSA. 2002-2006 Associate professor, Orthodontics and Pediatric Dentistry, School of Dentistry, UM 2006-2008 Director, Pediatric Dentistry, School of Dentistry, UM 2009-present Professor, Biologic and Materials Sciences, School of Dentistry, UM. 2010-present Director, Oral Health Sciences PhD program, School of Dentistry, UM PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Honors 1997 1998 2000 2004 2011 Faculty Research Foundation Award, second place, American Academy of Pediatric Dentistry. Faculty Research Foundation Award, first place, American Academy of Pediatric Dentistry. William J. Gies Award, Journal of Dental Research, AADR William J. Gies Award, Journal of Dental Research, AADR Paul P. Taylor Award, American Academy of Pediatric Dentistry C. Selected peer-reviewed publications (from more than 100 peer-reviewed publications) Most relevant to the current application 1. Hu JC, Lertlam R, Richardson AS, Smith CE, McKee MD, Simmer JP. Cell proliferation and apoptosis in enamelin null mice. Eur J Oral Sci. 2011 Dec;119 Suppl 1:329-37. PMID:22243264 NIHMSID354094 2. Chan HC, Estrella NM, Milkovich RN, Kim JW, Simmer JP, Hu JC. Target gene analyses of 39 amelogenesis imperfecta kindreds. Eur J Oral Sci. 2011 Dec;119 Suppl 1:311-23. PMID:22243262 NIHMSID354097 3. Wang SK, Chan HC, Rajderkar S, Milkovich RN, Uston KA, Kim JW, Simmer JP, Hu JC. Enamel malformations associated with a defined dentin sialophosphoprotein mutation in two families. Eur J Oral Sci. 2011 Dec;119 Suppl 1:158-67. PMID: 22243242 NIHMSID321456 4. Yamakoshi Y, Yamakoshi F, Hu JC, Simmer JP. Characterization of kallikrein-related peptidase 4 glycosylations. Eur J Oral Sci. 2011 Dec;119 Suppl 1:234-40. PMID:22243251 NIHMSID354087 5. Simmer JP, Richardson AS, Smith CE, Hu Y, Hu JC. Expression of kallikrein-related peptidase 4 in dental and non-dental tissues. Eur J Oral Sci. 2011 Dec;119 Suppl 1:226-33. PMID:22243250 NIHMSID318351 Additional recent publications of importance to the field (in chronological order) 1. Hu Y, Hu JC, Smith CE, Bartlett JD, Simmer JP. Kallikrein-related peptidase 4, matrix metalloproteinase 20, and the maturation of murine and porcine enamel. Eur J Oral Sci. 2011 Dec;119 Suppl 1:217-25. PMID:22243249 NIHMSID354099 2. Yamakoshi Y, Richardson AS, Nunez SM, Yamakoshi F, Milkovich RN, Hu JC, Bartlett JD, Simmer JP. Enamel proteins and proteases in Mmp20 and Klk4 null and double-null mice. Eur J Oral Sci. 2011 Dec;119 Suppl 1:206-16. PMID:22243248 NIHMSID354088 3. Smith CE, Hu Y, Richardson AS, Bartlett JD, Hu JC, Simmer JP. Relationships between protein and mineral during enamel development in normal and genetically altered mice. Eur J Oral Sci. 2011 Dec;119 Suppl 1:125-35. PMID:22243238 NIHMSID354103 4. Simmer JP, Hu Y, Richardson AS, Bartlett JD, Hu JC. Why does enamel in Klk4-null mice break above the dentino-enamel junction? Cells Tissues Organs. 2011;194(2-4):211-5. Epub 2011 May 6. PMID: 21546759 PMCID: PMC3178080 5. Smith CE, Richardson AS, Hu Y, Bartlett JD, Hu JCC, Simmer JP. Effect of Kallikrein 4 Loss on Enamel Mineralization: Comparison To Mice Lacking Matrix Metalloproteinase 20. J Biol Chem. 2011 Apr 6. 286(20):18149-60. PMCID: PMC3093887 6. Yamakoshi Y, Nagano T, Hu JC, Yamakoshi F, Simmer JP. Porcine dentin sialoprotein glycosylation and glycosaminoglycan attachments. BMC Biochem. 2011 Feb 3;12:6. PMCID: PMC3039539 7. Zealand CM, Botero TM, Boynton JR, Briskie DM, Hu JCC. Comparison of Gray Mineral Trioxide Aggregate and Diluted Formocresol in Pulpotomized Human Primary Molars. Pediatr Dent 2010 SepOct;32(5):393-9. PMID: 21070705 8. Chun Y-H P., Lu Y, Hu YY, Krebsbach PH, Yamada Y, Hu JCC, Simmer JP. Transgenic Rescue of Enamel Phenotype in Ambn Null Mice. J Dent Res. 2010 Dec;89(12):1414-20. PMCID: PMC3085845 9. Lee S-K, Seymen F, Lee K-E, Kang H-Y, Yildirim M, Tuna E B, Gencay K, Hwang Y-H, Nam KH, De La Garza RJ, Hu JCC, Simmer JP, Kim J-K. Novel WDR72 Mutation and Intracellular Localization. J Dent Res. 2010 Dec;89 (12):1378-82. Epub 2010 Oct 11. PMCID: PMC3144073 10. Lee SK, Lee EK, Kang HY, Jeong TS, Hwang YH, Nam KH, Kim S, Hu JCC, Simmer JP, Kim J-K. FAM83H Mutations Cause ADHCAI and Alter Intracellular Protein Localization. J Dent Res. 2011 Mar;90(3):377-81. Epub 2010 Nov 30. PMID: 21118793 D. Research Support PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Ongoing Research Support RO1-DE019622-03 Jan C-C. Hu (PI) 04/01/09-03/31/14 NIDCR Title: Why is Fam83h important for enamel formation? We proposed to (1) characterize the temporal and spatial pattern of Fam83h expression during odontogenesis and to determine its subcellular localization, (2) isolate Fam83H protein for structural and functional characterization, (3) identify Fam83H interacting proteins, and (4) determine if the expression of truncated Fam83h interferes with amelogenesis. RO1DE015846-07 James P. Simmer (PI) 9/1/2009-5/31/2014 NIDCR Title: Proteomics and Genetics of Enamel and Dentin. Five aims are proposed 1) to determine the temporal and spatial expression of Klk4 in ameloblasts during the secretory, transition, and maturation stages and in the underlying odontoblasts, 2) to characterize enamel formation in the absence of Klk4 expression, 3) to characterize the enzymatic activity of Klk4 on amelogenin, ameloblastin and enamelin, 4) to investigate the expression of protease activated receptors (PARs) by ameloblasts, and 5) to identify other organs and tissues that express Klk4. Role: Investigator. R01 DE019775-07 James Simmer (PI) 9/1/09-5/31/14 NIDCR Title: Functional Studies of Kallikrein4 Five aims are proposed (1) to determine the temporal and spatial expression of Klk4 in ameloblasts during the secretory, transition, and maturation stages and in the underlying odontoblasts, (2) to characterize enamel formation in the absence of Klk4 expression, (3) to characterize the enzymatic activity of Klk4 on amelogenin, ameloblastin and enamelin, (4) to investigate the expression of protease activated receptors (PARs) by ameloblasts, and (5) to identify other organs and tissues that express Klk4. Role: Investigator RO1 DE018020-05 Yasuo Yamakoshi (PI) 2/20/08-12/31/12 NIDCR Title: Structure and Function of Dentin Sialophosphoprotein Three Specific Aims are proposed to (1) identify the protease that catalyzes the initial cleavage of DSPP, (2) determine which DSPP-derived proteins are structural (long-lived) and which are transient (degraded), and characterize the structural/functional properties of the DSPP-derived proteins. Role: Investigator R56 DE11301-11 Jan C-C. Hu (PI) 07/01/10-06/30/12 NIDCR Title: Enamel and Enamelin Four specific aims are proposed to (1) determine the functional consequences of altered enamelin expression on crystal number and shape, (2) establish a transgenic system to assay the function of enamel proteins in vivo and use it to determine the functions of the enamelin N-terminal/32kDa and C-terminal cystine-rich domains, (3) discern whether reduced enamelin or cell pathology alters ameloblastin and/or amelogenin expression, and (4) express and purify recombinant enamelin for in vitro functional analyses. Completed Research Support RO1-DE11301-10 Jan C-C. Hu (PI) 07/01/03-12/30/09 NIDCR Title: Enamel without Enamelin The specific aims of this proposal are: 1. To characterize enamel formation in the absence of mouse enamelin expression 2. To characterize enamelin protein structure and function. PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page