Download PHS 398 (Rev. 9/04), Biographical Sketch Format Page

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)
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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)
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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)
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Biographical Sketch Format Page