Discover CCMB

2012Center for CraniofacialMolecular Biology

Contents2 Director's Message4 About CCMB5 Meet the Faculty

Featured Faculty6 Yang Chai12 Janet Oldak16 Michael Paine20 Harold Slavkin24 Songtao Shi28 Malcolm Snead

New Faculty Spotlight32 AmyMerrill-Brugger35 Ruchi Bajpai38 CCMBTeam40 Events&Activitiesies

Director'sMessageWelcome to the Center for Craniofacial Molecular Biology (CCMB) at the Ostrow Schoolof Dentistry, University of Southern California.CCMB is a research laboratory located on the Health Sciences Campus of the University ofSouthern California in Los Angeles. USC is proud to be a member of a small group of eliteresearch universities in the nation. CCMB is a world-renowned research center whereinnovative basic science research in craniofacial biology merges with cutting-edge clinicalpractice. The laboratory is funded through numerous federal and organization-sponsoredresearch grants. Many of these grants are from the National Institute of Dental andCraniofacial Research under which basic research is conducted into developmental,biochemical and molecular biological aspects of human development, with a specialemphasis on craniofacial structures in both health and disease. Specifically, our facultymembers are conducting research on diverse topics including (1) the molecular genetics oftooth development; (2) the cellular and molecular etiology of cleft lip and cleft palate andrescue; (3) enamel matrix formation and biomineralization; (4) transcriptional control ofcraniofacial development; (5) stem cell mediated craniofacial tissue regeneration andimmunology; (6) nanotechnology strategies for growth of bones and teeth; (7) stem cellsand the specification of neural crest cells; (8) human skeletal diseases; as well as manyothers.History has shown that the public derives immeasurable benefits from investment inbiomedical research in a wide array of health areas. Looking to the future of oral andcraniofacial research, it is clear that we are entering a momentous time for our center. As weplan for the future, we will continue to emphasize the importance of oral health and how itaffects the rest of the body. We will work closely with our colleagues to translate scientificdiscovery to practical health care. We will explore diverse funding sources to support ourresearch. We will make every effort to train the next generation of scientists who willcontinue to create new knowledge to benefit society. We will continue to advance scientificknowledge and promote innovation in order to reap the best rewards.I invite you to explore many of the exciting research projects conducted at CCMB anddiscover how our faculty, staff and students are working together to shape the future ofhealth care.Sincerely,

Yang Chai, D.D.S., Ph.D.ProfessorGeorge andMaryLou Boone Chair in Craniofacial Molecular Biology

Director, Center for Craniofacial Molecular BiologyAssociate Dean of Research

Herman Ostrow School of DentistryUniversity of Southern California

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The Center for Craniofacial Molecular Biology (CCMB) is theOstrow School of Dentistry's primary research facility; located in theheart of the University of Southern California's Health SciencesCampus.CCMB is home to a diverse group of world-class researchers in avariety of disciplines centered around structures of the craniofacialregion. Since its establishment in 1989, CCMB has been home toseveral major discoveries and has attracted top researchers fromaround the world. CCMB also serves as a bridge that connectsMedicine and Dentistry, allowing meaningful and productivecollaborations to exist between the Keck School of Medicine and theOstrow School of Dentistry.

CCMB receives its funding from numerous federaland organization-sponsored research grants, manyof which originate from the National Institute ofDental and Craniofacial Research (NIDCR)under which basic research is conducted intodevelopmental, biochemical, molecular andbiological aspects of human development, withspecial emphasis on craniofacial structures in bothhealth and disease.

In addition to highly-acclaimed researchers, CCMB is also comprisedof top-notch graduate students, post-doctoral fellows, researchtechnicians and administrators who work together effectively to fulfillthe center's mission to advance oral, dental and craniofacial researchtoward solving problems in health and promoting the well-being ofsociety.

About the Center

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From left: Yan Zhou, Malcolm Snead, Stephen Yen, Ruchi Bajpai, Matthew Lee, Amy Merrill-Brugger, Yang Chai,Janet Oldak, Songtao Shi, Anh Le and Michael Paine. Not pictured: Hal Slavkin, Mark Urata and MargaritaZeichner-David

“By mutual confidence and mutual aid - great deeds are done, andgreat discoveries made.”

- Homer

Meet the Faculty

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Yang Chai, D.D.S., Ph.D.ProfessorGeorge andMaryLou Boone Chair in CraniofacialMolecular BiologyAssociate Dean of ResearchDirector, Center for CraniofacialMolecular BiologyHermanOstrow School of Dentistry of USC

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TENACITY OF PURPOSEHighly-distinguised scientist, innovator, teacher, mentor, clinician and director of a world-class research organization...these are but a few hats that Dr. Yang Chai wears on a daily basisin pursuit of advancing craniofacial genetics and development research.

Dr. Yang Chai is not only the George andMaryLou Boone Professor of USC, but he is alsothe Associate Dean of Research at the OstrowSchool of Dentistry and serves as the Director ofthe Center for Craniofacial Molecular Biology(CCMB); these significant roles are part of a widearray of responsibilities that vie for his time andattention which he manages with a great deal ofaplomb.Dr. Chai is recognized around the world for hisgroundbreaking research in craniofacial genetics anddevelopment, most notably for his work on themolecular regulation of cranial neural crest (CNC)cells. His goals are to uncover the etiology andmolecular mechanisms that lead to certain oral andfacial birth defects, determine preventive measuresand discover how to reverse a malformation prior tobirth in order to spare children from complexsurgeries and the other hardships that come withsuch defects.Most recently, Dr. Chai and his collaborators fromthe Ostrow School of Dentistry were credited withadvancing the understanding of the genetic disordercalled Loeys-Dietz syndrome or Marfan syndrometype II which manifests with life-threatening birthdefects. This discovery may allow doctors toquickly diagnose and better treat the disease. Their

work was published in February 2012 in The Journalof Clinical Investigation.

Dr. Chai's commitment and contributions to dentaland craniofacial research have garnered him some ofthe field's most prestigious awards including beingelected as an American Association for theAdvancement of Science (AAAS) Fellow (2011);receiving the Distinguished Scientist Award forCraniofacial Biology Research from theInternational Association for Dental Research(2011), as well as the Method to Extend Researchin Time (MERIT) Award from the NationalInstitute of Dental and Craniofacial Research,National Institutes of Health (2010).

As a widely respected researcher and prolific authorof more than 100 scientific papers and numerousbook chapters, Dr. Chai serves on the editorialboard of Developmental Biology and Journal of Boneand Mineral Research. He is also on the Board ofScientific Counselors at the National Institute ofDental and Craniofacial Research for the NationalInstitutes of Health (NIH). He will soon begin toserve as the chair of the Board of ScientificCounselors at NIDCR, NIH. In addition, heserves on NIH study sections and reviews grantapplications for the Welcome Trust, MRC, andother international research organizations.

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Cranial Neural Crest Cells and CraniofacialMalformationsThe formation of cranial neural crest (CNC) cells is one of the key features of craniofacial development. CNC cellsgive rise to an array of cell types during embryonic development. Dr. Chai and his collaborators developed acomprehensive cell fate tracking system in which they are able to investigate the functional significance of a signalingmolecule in regulating the fate of neural crest cells (Chai et al., 2000). They found that transforming growth factor-beta (TGF-β) plays an important role in regulating the fateof CNC cells; specifically, conditional inactivation ofTgfbr2 (TGF-β type II receptor) in CNC cells causes cleftpalate and other craniofacial defects. The significance ofthis model is nothing short of groundbreaking since it hasprovided the opportunity to discover downstream signalingevents and the ability to test how manipulation of TGF-βsignaling may prevent and rescue cleft palate in mice andhumans. (Ito et al., 2003; Sasaki et al., 2006; Iwata et al.,2010, 2012 and unpublished data).

Tissue-tissue Interaction in Regulating TongueMorphogenesisAnother area of research that Dr. Chai and his colleagues are working on is understanding how cell-cell interactioncontrols tongue development. Their preliminary studies show that cranial neural crest (CNC) cells contribute to theinterstitial connective tissue, which ultimately compartmentalizes both intrinsic and extrinsic tongue muscles andserves as their attachments. Taking advantage of their neural crest- or mesoderm-specific Tgfbr2 mutant animalmodels, they designed studies to test the hypothesis that TGF-signaling controls the fate of CNCs as well asmesoderm-derived cells and regulates tissue-tissue interaction during tongue development. Ultimately, this study willprovide a better understanding of how the TGF-β signaling cascade regulates the fate of the CNC- and mesodermderived cells during normal craniofacial development and how signaling pathway disruption can lead to craniofacialmalformations.

Dr. Chai's research is currently focused on the following areas:

ToothMorphogenesis and JawboneRegenerationDr. Chai and his collaborators are also focusing on theinvestigation of a novel function for post-migratorycranial neural crest (CNC) cells in organ development andto demonstrate the utility of these CNC cells inregenerating craniofacial structures. They are currentlyperforming experiments to test their hypotheses thatSmad4 mediated BMP/TGF-β signaling and theirdownstream target genes are crucial for mediating tissue-tissue interactions and controlling the fate of epithelialand dental mesenchymal cells during tooth rootdevelopment. The study has already yielded thediscovery that post-migratory cranial neural crest (CNC)cells maintain mesenchymal stem cell (MSC)characteristics and show potential utility for theregeneration of craniofacial structures.

(1) Cranial neural crest cells and craniofacial malformations, (2) TGF-beta signaling and craniofacialmorphogenesis, (3) Tissue-tissue interactions in regulating tongue morphogenesis, and (4) Molecular regulationof tooth root development.

"We are interested in learning how different parts of a tooth develop. We have done intensive studies looking atwhat controls crown formation during tooth development and more recently, we have branched out in the area ofroot formation. We are learning how root formation is controlled through tissue-tissue interaction with the hopethat with some of the stem cell biology we are working on, we can use that to regenerate the root or jawbone, so thatwe can change the way we restore missing teeth."

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“We are not just working on

animal models just for the

sake of discovery, but using it

to gain a better

understanding of what is

wrong in human disease.

This research puts us in the

translational side of science

which is really exciting. If we

understand the cause of a

congenital birth defect, we

can use the information to

provide better diagnosis and

ultimately, prevention of the

malformation.”

Dr. Chai's extensive accomplishments are not limitedto his contributions as ahighly decorated scientist,but also extend to hisleadership and mentoringabilities that have proven tobe effective in inspiringyounger faculty and studentresearchers. Howeverweighty the demands are ofhis work as a researcher,Dr. Chai still finds time toteach the Head and NeckAnatomy class for thestudents at the OstrowSchool of Dentistry. Histraining in anatomy andoral-maxillofacial surgerymake him an ideal candidate to teach head and neckanatomy which is fundamental to oral health care.“Teaching makes me appreciate theimportance of anatomy, it is a greatexperience and I love the interaction with thestudents." His belief in encouraging the next

generation of scientists is evident; he currentlymentors four dentalstudents (one of whomwon the 2012 bestundergraduate dentalstudent research award)and two undergraduateswho are interested indentistry and medicine.

Dr. Chai also maintainsan active clinicalpractice. “I reallyvalue my clinicaltraining andmyclinical practicehelps me focus onthe areas of researchthat can make a

difference for my patients”. His clinical practicekeeps him in touch with the most pressing needs ofhis patients and has served as an inspiration on morethan one occasion. In fact, his jawbone regenerationresearch was directly inspired by his clinical practice.

TEACHER,MENTORANDCLINICIAN

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Front row (from left): Julie Mayo, Akiko Susuki, Arum Han, Jifan Feng, Gilian Zhong, CarolinaParada, Pedro Sanchez Back row (from left): Jingyuan Li, Thach-Vu Ho, Yang Chai, RichardPelikan, Junichi Iwata, Mark Urata, Hu Zhao.

Since his appointment as Directorin 2007, Dr. Chai has devotedsignificant efforts to firmly establisheminent status for CCMB. Whilethe Center has had many successesin competing for federal grants andits impressive research portfoliocontinues to grow, the hallmark ofCCMB's many triumphs, accordingto Dr. Chai, lies in its highly

collaborative environment andexceptionally supportive faculty.In the recent competition for theARRA (American Recovery andReinvestment Award) grants fromthe NIH, CCMB faculty achievedan astonishing 67% success rate.These research grants have allowedCCMB faculty to expand theirresearch portfolio, recruit newfaculty, improve researchinfrastructure and establish newcollaborations throughout theworld.Dr. Chai also points to CCMB'sother strengths, including itslocation at the heart of the HealthSciences Campus which provides itsinvestigators with the ability toutilize many of the University's core

facilities and the implementation ofimportant support services that notonly support its own faculty, butattract many others from all overUSC.Dr. Chai notes that CCMB hasnow extended its collaborative reachby working with human geneticistsand clinicians like Dr. PedroSanchez and Dr. Mark Urata fromChildren's Hospital, Los Angeles(CHLA) who now have dualappointments with the OstrowSchool of Dentistry and the KeckSchool of Medicine. Thesecollaborations have proven to beadvantageous in bridging the gapbetween basic research and clinicalpractice.

“CCMB is foremost is a collaborativeenvironment. There is extensive interactionamong the faculty with each group having its ownarea of expertise. It is such a fun and happy placeto work in; you only have to look at our facultyand see how supportive they are of each other.Many people, including myself, feel that CCMBhas such great potential. We will continue toexpand our research, attract promising scientistsand be the envy of the craniofacial researchcommunity.”

CCMB facultyachieved an

astonishing 67%success rate in therecent competitionfor the ARRA grants

from the NIH.

DIRECTOROFTHECENTERFORCRANIOFACIALMOLECULAR

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Dr. Chai shares his life with hiswife and two daughters. He creditstheir unwavering support for beingable to accomplish all that he does.Life in the Chai household is hectic,but satisfying. Dr. Chai's wife alsohas a demanding career working incancer epidemiology and his twodaughters excel in academics andsports; the older one is nowattending USC as a freshman andthe younger one has startedhighschool. The family enjoysgardening and traveling as timepermits.

Groundwork is carefully being laid for CCMB's future. Dr. Chaimentioned that he plans to continue to foster the successes of CCMB'sfaculty in basic research, as well as expand into translational research inorder to compete in the intense research arena.There is also intent in the very near future to recruit more promisingjunior faculty in support of this endeavor, along with plans to continue toimprove the Center's infrastructure to make it more ideal for cutting

edge research. Dr. Chai is alsolooking to increase collaborationwithin the University and othernational and internationalorganizations.He cites the hiring of Dr. AmyMerrill-Brugger and Dr. RuchiBajpai as examples of CCMB'ssuccess in recruiting talentedjunior faculty as part of acomprehensive plan to supportthe center's growth and futuredirection.

ALOOKAHEAD

For more information about Dr. Chaiplease visit the CCMBwebsite at:

www.usc.edu/hsc/dental/ccmb

"We want to continue tobuild upon our strengths incraniofacial developmentand tissue regeneration,expand into translationalresearch and continue toattract world-classscientists.”

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Janet Oldak,M.Sc., Ph.D.ProfessorHermanOstrow School of Dentistry of USC

CRACKING THE CODEThe quest to be able to grow tooth enamel or similar synthetic materials has been a long butfruitful journey for Dr. Janet Oldak, who hopes her life's work will help other researchersbeyond dental science.

For nearly two decades, CCMBresearchers have been studying howdental enamel is formed with thegoal to one day be able to grownatural tooth enamel and/or createsynthetic materials that can be usedas alternative dental restorativematter. Dr. Janet Oldak is arenowned expert on tooth enamelformation and structural biology.She integrates physical chemistry, biochemistry,molecular biology, biotechnology, and biomaterialsciences in the study of mineralization of enamel. Hergroundbreaking work has already resulted in one U.S.patent for Tooth Enamel Inspired Materials for Dentaland Biomedical Application (Patent No. US 7,132,015B2).

In 2011, Dr. Oldak was appointed Professor of theDivision of Biomedical Sciences in the Ostrow School ofDentistry. Her accomplishments to date, include beingthe President Elect for the American Association of

Dental Research (AADR) of SouthernCalifornia (2012); being Co-Chair of the10th International Conference on theChemistry and Biology of MineralizedTissues (2007-2010); serving in the SpecialGrants Review Committee (SGRC) of theNIDCR Standing Study Section(2007-2009); being a member of the NIHMusculoskeletal Tissue Engineering StudySection (MTE) (2011-2015); and being

elected President of the Mineralized Tissue Group ofthe International Association of Dental Research(IADR) and American Association of Dental Research(AADR) (2007-2008).

Dr. Oldak is also a prolific author of 90 articles in peer-reviewed journals and numerous book chapters, and hasserved on the Journal of Dental Research’s Editorial Boardand the National Institute of Dental and CraniofacialResearch (NIDCR) Ad Hoc Study Sections. She iscurrently an Associate Editor of Connective TissueResearch.

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"My ultimate goal is to help scientistsdevelop new dental materials that moreclosely mimic the structure and function ofnatural tooth enamel. In addition, I seek toexplore novel fundamental structuralprinciples by which proteins interact withtheir targets and to investigate theprevalence of intrinsically disorderedproteins in tooth biomineralization."

Since 1999, Dr. Oldak has beenreceiving ongoing research supportmainly through funding from NIH-NIDR that allows her to continueher objective to understand theprinciples that govern the formationand mineralization of dental enamelby learning how the intricate matrixof proteins, enzymes and mineralscome together to form a remarkablebio-ceramic. Dr. Oldak’s laboratoryis currently focused on the followingresearch projects, some incollaboration with other investigators within and outsideof the University: 1) Molecular Mechanisms ofAmelogenin Self-Assembly, 2) Investigation ofAmelogenin Configuration by NMR Spectroscopy, 3)

Amelogenin Interactions with OtherEnamel Proteins and Lipids, 3)Amelogenin-Mineral Interactions, 4)Biomimetic Strategies For Synthesisof Enamel Inspired Material, 5)Protein Proteolysis and MineralCrystal Growth, 6) IntrinsicDisorder in Proteins Interacting withMineral, 7) Amelogenin-apatiteNanocomposite Coatings to ImproveTitanium Implants.

In addition to her existing researchprojects, Dr. Oldak plans to continue her collaborationwith Dr. Jim De Yoreo of the Molecular Foundry atLawrence Berkeley National Laboratory to look at earlystages of mineral nucleation and subsequent growth ascontrolled by enamel proteins and proteinases in vitro.

“The basic principles that we’velearned from how proteins function,how they interact with differenttargets and fulfill different functionscan have a profound impact on otherareas of research. We have ideasabout developing other biomedicalmaterial applications, such asmanipulating the coating of titaniumimplants to improve integration,promote cell growth andregeneration.”

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Their intent is to explore cooperative protein-proteininteractions in vitro and in vivo, and to continue effortsto design and develop biomimetic strategies for bio-inspired re-mineralization of enamel.

Dr. Oldak spends the majority of her time in research,but like all other CCMB faculty,she is also involved in teaching inthe Keck School of Medicine(Protein Chemistry), and facilitatesProblem Based Learning (PBL) andCraniofacial Biology (CBY) coursesfor the Ostrow School of Dentistry,among others. For the last tenyears, Dr. Oldak has mentored agreat number of dental students aspart of CCMB’s student research

program. She believes in the enriching value ofintroducing students to research which she haswitnessed to have an empowering effect.

The objective of reconstructing dental enamel on toothsurfaces continuous to be a challenge, but Dr. Oldak is

undaunted in her pursuit of cracking theproverbial code. The impact of beingable to do so has implications that gobeyond dental science. She hopes thather research efforts will have high impactand prove to be useful to other scientistsin understanding systems and synthesisof other materials.

“Over the last 5 to 10years, I’ve opened mylaboratory to any studentwho is interested. I thinkit is important to invest inthe next generation ofscientists like those beforeus have.”

Dr. Oldak shares her life with her husband of25 years who is a Professor of ElectricalEngineering, her 22 year-old daughter who is arecent USC graduate and her 17 year old son.She cites yoga and 5K-10K distance running asactivities that she enjoys outside of spendingtime with her family.

CURRENTRESEARCHFOCUS

Intrinsically Disordered Proteins in BiomineralizationThe long term objective of the proposed research is toadvance the understanding of the role of extracellular matrixprotein fragmentation in enamel and dentin, with a focus onthe analysis of folding and the degree of disorder in thesecondary structures of key proteins and polypeptides.

Matrix-BasedMineral (MBM) Enamel BiomimeticsThe major goal of this project is to understand the generalprinciples that apply to the formation of dental enamel and todevelop biomimetic strategies for the fabrication of enamel-like materials in-vitro.

Biomimetic Coatings on Titanium Implants for PromotingPeriodontal RegenerationThe long-term objective of this study is to develop dentalimplants that will promote the formation of a periodontalattachment apparatus on their surface around them. Thestrategy is based on treating the implant surface to create anamelogenin-calcium phosphate nano-composite coating thatwill induce periodontal regeneration.

To find out more information about Dr.Oldak, please visit CCMB's website at

www.usc.edu/hsc/dental/ccmb/15

Michael L. Paine, B.Sc., B.D.S., Ph.D.Professor of DentistryDirector of the Graduate Program in Craniofacial BiologyHermanOstrow School of Dentistry of USC

PUSHING THEKNOWLEDGE BASECCMB is home to some of the world’s foremost experts in craniofacial development andbiology. Among the many innovators in the Center is tooth formation expert, Dr.MichaelPaine, who has devoted his two decades-long career to understanding dental enamelformation and bio-mineralization.Dr. Paine received his Ph.D. in Pathology in 1993from the University of Sydney in Australia. In 1999,he obtained a Certificate in Periodontology from theUniversity of Southern California. In March of 2011,Dr. Paine was appointed Professor of the OstrowSchool of Dentistry of USC. In addition to his work asa dedicated researcher, Dr. Paine is also the Director ofthe Graduate Program in Craniofacial Biology and co-directs the Keck School of Medicine’s Masters ofScience in Clinical and Biomedical Investigations. Hisconsiderable service to USC includesparticipating in the University’sInstitutional Review Board (since 2003);being Vice-Chair of the Ostrow School ofDentistry’s “CurriculumCommittee” (2006-2009); serving as Co-Chair of the “Health ProfessionsSubcommittee” of the UniversityCommittee on Curriculum (UCOC); andbeing a member of the “PolicyCommittee” of UCOC and thePostdoctoral Affairs Advisory Committee(since 2011).

His dedication and expertise in craniofacial researchhas won Dr. Paine many well-deserved accolades, aswell as high demand for his leadership. Since 2009, hehas been a standing member of the National Instituteof Dental and Craniofacial Research (NIDCR) SpecialGrants Review Committee (SGRC) and was appointedas its Chair this year. Currently, he is also thePresident Elect of the Mineralized Tissue group of theAmerican Association of Dental Research (AADR), aswell as a member of the American Association of

Dental Research (AADR)“Constitution Committee”. Dr. Paineis also an esteemed member of thefollowing professional organizations:American Association for theAdvancement of Science (since 1992),American Association for DentalResearch and American Society for CellBiology (since 1994), as well as theAmerican Academy of Periodontology(since 1995) and the American DentalEducation Association (since 2009).

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Dr. Paine is the author of more than80 peer-reviewed journal articles andbook chapters, as well as acting as anad-hoc reviewer for over 30 high-impact journals.

In 2011, Dr. Paine was selected asone of only four recipientsnationwide of the InstitutionalTraining for Dental andCraniofacial Research WorkforceGrant, also known as the T90training grant, in the amount of$2.6 million from the NIDCR.The grant is designed to providesupport for a select cadre of scholarsseeking either a formal Ph.D.degree education or post-doctoraltraining with a major focus ondental, orofacial and craniofacialhealth-related disease processes.

Dr. Paine’s main research focus ison dental enamel formation and theproteins involved in the process.More recently, his interest has beencaptured by the regulation of pH

during enamel formation and howthe cells that produce enamel controlthe pH conditions, so that enamelsform properly without major defects.

Like all members of CCMB'sfaculty, Dr. Paine is involved incollaborations within the Center(Malcolm Snead and Janet Oldak)and other areas of the University,including faculty from the USCSchool of Pharmacy (Paul Beringerand Curtis Okamoto).

In addition to Dr. Paine’s dedicationto research, he is committed tofostering the success of the nextgeneration of scientists. Over theyears, he has mentored students aspart of CCMB’s summer researchprogram and has been involved inteaching Ph.D. and Masters ofScience candidates.

CCMB’s eminent status is due tosignificant efforts and contributionsmade by faculty like Dr. Paine. Thepotential applications of his workexceed the boundaries of dentalscience and serve to further cementthe Center’s reputation as a leader incraniofacial biology research.

“What we are trying to do isidentify proteins, includingion transport proteins,residing in enamel cells thatare essential for enamelformation. This has resultedin discoveries that manysyndromic medicalconditions resulting fromknown gene mutations may,or actually do, also includean unrecognized dentaldisease component. Suchdiseases include proximalrenal tubular acidosis, cysticfibrosis and peroxisomaldisorders."

“The future of dental education and support for biomedical research require investmentin the selection and training of tomorrow’s scientists, whether they are basic,translational or clinical researchers. Our objective is to educate the next generation ofresearchers so that they will be able to address the nation’s health-related needs in dental,oral, and craniofacial research".

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Dr. Paine shares his life with his wife and 12 year old twinboys whose interests in sports (basketball, college andprofessional football) have recently spurred his own. Dr.Paine enjoys gardening, reading and woodworking, asidefrom enjoying time with his family.

AREASOFRESEARCH

MolecularMechanisms for Extracellular pHControl DuringAmelogenesisSponsor: National Institute of Dental ResearchPeriod: 9/17/2009-06/30/2015

The connection between pH regulation and enamelmineralization is poorly understood. Animal models and patientswith disease states caused by mutations to genes involved withacid/base homeostasis frequently have dental defects. Three suchproteins are the anion exchanger (AE2), the electrogenic sodiumbicarbonate cotransporter (NBCe1) and the cystic fibrosistransmembrane conductance regulator (CFTR), which is achloride channel, is directly associated with AE2 function.Clinical observations suggest that AE2, NBCe1 and CFTR eachplay important roles in enamel mineralization (amelogenesis).This project is to better understand the physiological andbiochemical functions of AE2, NBCe1 and CFTR inamelogenesis. With a better understanding of pH regulation anddental disease, earlier and more accurate dental diagnoses, andmore appropriate dental treatment options will be made availableto affected individuals.

EnamelMatrix Protein InteractionSponsor: National Institute of Dental ResearchPeriod: 3/01/2000-03/31/2013

The goal of this project is to characterize protein-proteininteractions involving the enamel extracellular matrix proteins, aswell as proteins integral to the plasma membrane of ameloblastcells, and characterize how these interactions regulate enamelformation. To achieve this, the molecular biochemistry of threepotential membrane-bound receptors (LAMP1, LAMP2 andCD63) of the structural enamel matrix proteins are beingstudied. Knowledge gained from this and related studies maylead to better dental and non-dental materials, or biomimetics.This data will be critical in the pursuit to regenerate an entiretooth, which is the ultimate goal of this and other related studies.

In a recent publication in theJournal of Cell Physiology(published August 2011), Dr.Paine and his colleaguesexploited the two-step processof enamel formation to identifythe genetic events drivingenamel mineralization byconducting a comprehensivegenome-wide profiling of theenamel organ. They identifiedgroups of maturation-associated genes whosefunctions are linked to keymineralization processesincluding pH regulation,calcium handling, and matrixturnover. The study provides astrong foundation forimproving the basicunderstanding ofbiomineralization and itspractical applications inhealthcare by providing thefirst global overview of thecellular machinery required forenamel maturation.

To find out more information about Dr.Paine, please visit CCMB's website at

www.usc.edu/hsc/dental/ccmb/19

Harold Slavkin, D.D.S.Professor of DentistryFormer DeanHermanOstrow School of Dentistry of USC

LEGACY FOR THE AGESFormer Dean of the Ostrow School of Dentistry of USC and founder of the Center forCraniofacialMolecular Biology, Dr. Hal Slavkin continues his inimitable journey as apioneer in craniofacial biology.

It would be difficult to think of theCenter for Craniofacial MolecularBiology (CCMB) without callingto mind one its most distinguishedleaders and founding director, Dr.Harold Slavkin. Over the courseof nearly half a century, Dr.Slavkin has been both witness andinfluential contributor tocraniofacial biology’s emergence asa major multidisciplinaryconcentration whose advancementshave made a profound impact onsociety at large and spurred atorrent of research activities inother biomedical fields.

As one of Ostrow School ofDentistry’s most distinguishedalumni, Dr. Slavkin establishedCCMB in 1989 specifically todirect and advance oral, dental andcraniofacial research. In 1995, Dr.Slavkin was recruited to becomethe 6th director of the NationalInstitute of Dental andCraniofacial Research (NIDCR)within the National Institutes ofHealth where he promotedresearch on oral health disparities,

craniofacial biology, innovations inbiomaterials, as well as focusedattention on training andcollaborations with otherorganizations. In 2000, Dr.Slavkin returned to his alma materand served as the Ostrow School ofDentistry’s 11th Dean where hechampioned learner-centerededucation, access to oral healthcarefor the underserved and dynamicbasic, translational and clinicalresearch until he stepped down in2008.

Dr. Slavkin went on sabbatical in2009 and returned to USC in 2010as a tenured professor with CCMBwhose time is now divided betweenteaching, research and writing. Heuses his rich experience andexpertise in research and academiato help postdoctoral researchersand graduate students to focustheir research, and improve theirthinking and communication skills.Dr. Slavkin collaborates with otherfaculty, namely Dr. Yang Chai,

who is the current director ofCCMB, and Drs. Pedro Sanchezand Mark Urata from Children’sHospital, Los Angeles (CHLA).He also collaborates with severalresearch teams from KyotoUniversity in Japan and jointly,they have recently published papersfocusing on the development ofgenetically defined mouse modelsfor human craniofacial syndromes.The most recent paper, Id2Controls Chondrogenesis ActingDownstream of BMP SignalingDuring Maxillary Morphogenesiswas published in Bone this pastJanuary .

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To date, Dr. Slavkin is still heavily involved intrying to increase access to oral healthcare for thedisadvantaged segments of the population,mainly the poor elderly and children. Thisendeavor started during his tenure as Director ofNIDCR where he led the charge to produce thefirst Surgeon General’s Report titled Oral Healthin America which was released in May 2000.

His current involvement extends to traveling tovarious governmental agencies to provide experttestimony and act as an advocate for theunderserved to be provided access to oralhealthcare.

Dr. Slavkin also served on an Institute ofMedicine (IOM) committee tasked withassessing the current oral health care system andrecommending strategic actions for theDepartment of Health and Human Services(DHHS) to improve oral health and oral healthcare in America. The report of the results of thestudy, Advancing Oral Health in America, waspublished in April of 2011.

“When science works, the 3Cs: Communication, Collaboration and Coordination, arealigned and are very effective. Science has evolved from being a solo act, to a team sport.It takes open international communication; it takes willingness and expertise forcollaboration; it takes the ability to coordinate the control of the team’s activities andgiving credit when appropriate to whom it’s due."

"At the moment, there are 110million Americans who do not haveaccess to oral healthcare. It's alwaysbeen in my consciousness...to try togain access to oral healthcare for thedisadvantaged population."

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Last October, Dr. Slavkin received the Larry Meskin/Ed Shils Award which recognizes outstandingcontributions in educating the public on the importance of oral health, providing educational opportunities forthose in the dental industry and profession, or demonstrating innovative care, policy or service models. Theaward was presented to Dr. Slavkin in Philadelphia, Pennsylvania.

In the coming months, Dr. Slavkin will be focusing on activities related tohis recently published book, The Birth of a Discipline: Craniofacial Biology,where he elucidates through personal narrative how craniofacial biology hasevolved and how the advancements in the field came about as a result of theconvergence of ideas and significant efforts from many talented individualswhose focus was to benefit those with congenital or acquired malformationsof the face, bringing about considerable scientific and public healthadvances.

The proclivity to discover, to create and to inspire is highly evidentin and permeates all facets of Dr. Slavkin’s life from his dedicationto craniofacial biology and improving healthcare access, to his loveof sailing and painting watercolors (see left). He shares his lifewith his wife, Lois, their four married children and eightgrandchildren.

To find out more information about Dr.Slavkin, please visit CCMB's website atwww.usc.edu/hsc/dental/ccmb/

Published in June 2012,

The Birth of a Discipline: Craniofacial Biology

may be purchased at http://store.dentalaegis.com

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Songtao Shi, D.D.S., Ph.D.Professor of DentistryHermanOstrow School of Dentistry of USC

LEADING THECHARGEAs stem cell research continues to give rise to novel scientificbreakthroughs, Dr. Songtao Shi is leading the charge inchanging the way human diseases and their cures are understoodand identified.For many scientific discoveries, chanceinteraction plays a great part, but anastute mind is needed to recognize itssignificance. Inspired serendipity ishow Dr. Songtao Shi made alandmark discovery that deciduous(baby) teeth contain stem cells. AsDr. Shi tells it, when his then-six-year-old daughter, Julia lost a tooth,they looked at it carefully and noticedred-colored tissue inside. Since Dr.Shi’s previous work had alreadydemonstrated that extracted adultwisdom teeth contained stem cells inthe pulp at the center of the tooth, hedecided to find out if the same wastrue for deciduous teeth. What Dr.Shi found then are what we now knowas SHED, stem cells from humanexfoliated deciduous teeth, whichbelong to a classification of stem cellscalled mesenchymal stem cells(MSCs).

MSCs have been shown to be able torepair damaged cardiac tissue andgenerate new nerve, fat, cartilage,muscle, and bone tissue. Dr. Shi’sdiscovery was the subject of manyarticles covered by news organizationsaround the world, including theWashington Post, ScientificAmerican, ABC News, and UnitedPress International. Since then, Dr.Shi and his colleagues have beenmaking other landmark discoveriesidentifying dental pulp stem cells,periodontal ligament stem cells, rootapical papilla stem cells, tendon stemcells, gingiva stem cells, sclera MSCs,and benign tumor MSCs from keloids.Their novel and landmark findingshave paved the way for other scientiststo investigate oral tissue-derived stemcells and their use for tissueengineering and disease modeling.

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Dr. Shi received his Ph.D. inCraniofacial Biology from theUniversity of Southern Californiain 1994. Prior to joining thefaculty in CCMB in 2006, Dr.Shi served as a PrincipalInvestigator and Clinical Fellowfor eight years at the NationalInstitute of Dental andCraniofacial Research (NIDCR)where he made the discovery ofthe existence of SHED.

Dr. Shi is a prolific authorof more than 124 peer-reviewed articles in avariety of high-impactscientific journals, ofwhich, he served as thefirst or correspondingauthor. Dr. Shi has servedon numerous committeesand boards includingbeing the Scientific Editor forPLoS ONE and Associate Editorfor Oral Diseases. Currently, he ison the editorial boards of StemCell Research & Therapy, WorldJournal of Stem Cells, and theChinese Journal of Dental Research.

Dr. Shi is Changjing Scholar inthe Fourth Military MedicalUniversity, DistinguishedVisiting Professor in TongjiUniversity, and Visiting Professor

in XiangYa School of Medicine& Stomatology, Central SouthUniversity (CSU). A trainedpediatric dentist, Dr. Shi holds adental license from the State ofCalifornia with clinicalexperience working at a NIHhospital and in private practice.This background has enabled Dr.Shi to be a highly qualifiedtranslational researcher studying

orofacial disorders and explorecures for orofacial diseases.

Currently, Dr. Shi’s research isfocused on understanding themechanisms of MSC associateddiseases, developing newexperimental disease models, andexploring the feasibility oftranslating these benchdiscoveries to clinical therapies.His groundbreaking researchcontinues to push the knowledge

base which has implicationsbeyond dental science. Amonghis recent findings, Dr. Shi andhis collaborators were the first touse MSCs to treat systemic lupuserythematosus (SLE), as well asperiodontitis in animal modelsand patients. They were also thefirst to generate bisphosphonate-related osteonecrosis of the jaw-like disease (BRONJ) in mouseand swine models.

Very recently, Dr. Shi and hiscolleagues discovered that apreviously unrecognizedmechanism known as the FAS/FAS-ligand pathway was the keyto the therapeutic benefits ofsystemic infusion of MSCs for avariety of auto-immune diseasesand may therefore represent anew functional role of receptor/ligand in cell therapies. Thisstudy raises tantalizingpossibilities with regards to theapplication of this approach forother autoimmune disorders andorgan transplantation. Thedetails of the discovery werepublished in the May 2012 issueof Cell Stem Cell.

“We are always looking for ways to better useMSCs to cure diseases and understandtheir mechanisms. We are trying to understand one way human disease is linked to stemcells with the hope that the knowledge we collect along the way will lead to cures and/orprevention. Perhaps one day we’ll find that human diseases are linked to stem celldisorders and also discover a cure…for now we apply our knowledge to pioneer the use ofMSCs to cure diseases.”

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Another recent discovery by Dr. Shi and his colleaguesrelates to the potential of MSCs as a promising sourcefor bone generation. They presented findings thatprovide novel insight into how host immune systemscommunicate with transplanted MSCs during boneformation and repair. Systemic infusion of MSCs andlocal administration of aspirin markedly improvedbone regeneration. The details of the study werepublished in the December 2011 issue of NatureMedicine.

Dr. Shi attributes the success of his research to thediligent efforts of his team. “We have a goodteam…a dedicated team who is changingCCMB in terms of science. Eachmemberknows they are making a difference and it ispart of what keeps them pushing forward todiscover mechanisms to cure diseases andadvance stem cell therapy."

Like all faculty at CCMB, Dr. Shi performs otherfunctions in addition to research. Dr. Shi is alsoinvolved in the Clinical and Translational Health

Sciences Initiative. He also teaches courses for dentalstudents of the Ostrow School of Dentistry.Performing and promoting translational research is ofgreat importance to Dr. Shi. He believes thattranslational research helps scientists understanddiseases and find their cures faster, which in turnbenefits patients that desperately need them. Hebelieves that expansion in translational research willonly push CCMB even further as an elite researchorganization.

To find out more information about Dr.Shi, please visit CCMB's website atwww.usc.edu/hsc/dental/ccmb/

"Being a CCMB faculty member meansthat not only do we conduct research,but we also teach and serve oncommittees…we are educators withresponsibilities to the next generationof scientists, not only Ph.D. candidates,but dental students as well.”

Dr. Shi shares his life with his wife, daughter and son. Thefamily loves to travel and experience different cultures whenevertime permits.

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Malcolm Snead, D.D.S., Ph.D.Professor of DentistryChair of the Division of Biomedical SciencesHermanOstrow School of Dentistry of USC

THE GREATER GOODDr.Malcolm Snead is arguably one of the most compelling figures in CCMB not just for thesheer breadth of his knowledge of craniofacial biology, but also for his pursuit of not only hisown interests, but also in service of his peers, students and the University at large.To endeavor to list all of Dr. Snead’s accomplishmentsas a scientist, teacher, and mentor is not a smallundertaking by any means. His contributions tocraniofacial biology have garnered him some of thefield’s most prestigious awards including the FullbrightSenior Specialist Award in 2007; the Research in OralBiology Award in 2001; and the Methodto Enhance Research In Time (MERIT)award from the National Institute forDental and Craniofacial Research(NIDCR) in 2000.Dr. Snead is also a prolific author of morethan 110 publications, as well as a reviewerof 15 high-impact journals and is currentlyon the editorial boards of the followingpublications: Journal of BiologicalChemistry, Journal of Bone and Mineral,Research, Critical Reviews in Oral Biologyand Medicine, Journal of CraniofacialGenetics and Developmental Biology,International Journal of Oral Biology andOrthodontics and Craniofacial Research.

Dr. Snead is a renowned expert in biomimetics whoselong-term research goal is to understand the geneticprocess underlying the creation of teeth and to use thatknowledge to make biomimetics, or biologicalsubstitutes, not only for teeth, but for other parts of thebody, as well.

His expertise has earned Dr. Sneadmany well-deserved recognitions fromwithin and outside of USC, as well ashigh demand for his guidance. He is amember of a multitude of prominentprofessional organizations, includingthe American Association of DentalResearch and the International Societyfor Stem Cell Research, among others.Most recently, Dr. Snead was asked topresent an overview on the aspects ofenamel biomineralization in theGordon "Frontiers of Science"Conference on August 19, 2012.

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There is so much more to Dr.Snead than his considerableknowledge and value as a highlyaccomplished biologist. Hisscientific accomplishments arerivaled only by his long standinghistory of service, most of which areto the University, including butcertainly not limited to serving asthe Associate Dean of Research forthe Ostrow School of Dentistryfrom 2001-2006. Currently, Dr.Snead is also presiding as the Chairof the Division of BiomedicalSciences, who is responsible formore than half of the curriculum inthe dental school. He also serves onvarious University committeesincluding the Provost AcademicLeadership Development Program.

Like all CCMB faculty, Dr. Sneadalso takes part in fostering thesuccess of the next generation ofscientists. In fact, he helpedestablish CCMB’s summer researchprogram during Dr. HaroldSlavkin's tenure as Dean of theOstrow School of Dentistry. Theprogram was aimed at locating five

to ten entering dental students whomay be interested in a career inresearch. In addition to hisinvolvement in the summerprogram. Dr. Snead also finds timeto mentor new faculty. His effortswere recognized and rewarded whenhe was selected (out of four hundrednominations) to receive the USC

Mellon Mentoring Award in 2010;a testament to his commitment andeffectiveness as a mentor. Over theyears, Dr. Snead has won numerousawards which he would often sharewith his colleagues. The successthat he has enjoyed in academiaover the years seems to be temperedwith humility and the need to giveback, as evidenced by hisconsiderable service and willingnessto pass on the knowledge that hehas amassed so far.

Dr. Snead would like CCMB to berecognized for the depth ofeminence it provides the University;not just for scholarship, but for themany roles that each faculty istasked with.

“CCMB faculty membersdo a lot more than whatthey are widely known forwhich is world-classresearch and publication.Many of us also havesignificant roles in theadministration of theOstrow School ofDentistry, includingparticipating in itseducational mission,faculty mentoring andUniversity reviewprocesses."

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To find out more information about Dr.Snead, please visit CCMB's website atwww.usc.edu/hsc/dental/ccmb/

When asked about the future of his work, Dr.Snead shared an anecdote about thephenomenon of the migration of Monarchbutterflies from Canada to South America. Hesaid that it takes three generations of butterfliesto make the complete trip. When the firstgeneration dies, the second picks up where theyleft off, continuing the journey until they perish,at which time the third generation proceeds tocomplete it. He notes that the same is true inresearch; work by the previous generation istaken to the next level by the next generation.

AREASOFRESEARCH

Determination and Expression ofAmelogenin Gene ProductsThe major goals of this project areto test the hypothesis thatamelogenin gene regulation isdependent upon a cascade of signalsprovided during instructivesecondary germ layer interactionserving to pattern oral epithelium tothe ameloblast phenotype.

Nanotechnology Strategies forGrowth of Bones and TeethThe major goal of this project is todevelop molecularly designedpeptide nanostructures that cantrigger differentiation of progenitorcells and mineralization inphysiological media with featuresthat mimic enamel or bone matrix.This research will guide thedevelopment of synthetic,nanostructured templates that canbe used for enamel or boneregeneration and repair.

Cell andGenetic Approaches toEnamel BiomimeticsThe major goal of this project is todetermine the effects of selectedtooth specific proteins on mineraldeposition and composition in vitro;using transgenic animals as part of again function test, determine theeffects of excessive amounts oftuftelin and ameloblastin proteinson tooth biomineralization in vivo.

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Amy E.Merrill-Brugger, Ph.D.Assistant Professor

HermanOstrow School of Dentistry of USCKeck School ofMedicine of USC

Dr. Amy Merrill-Brugger joined CCMBin 2010 after an exhaustive searchinvolving 78 applicants. She is one oftwo recent faculty additions to CCMBwho is intent on uncovering diseasemechanisms of craniofacial disorders andthe subsequent advancement of therapiesfor detection, treatment and ultimately,the prevention of those birth defects.Dr. Merrill-Brugger received her Ph.D.in Biochemistry and Molecular Biology in2005 from the University of SouthernCalifornia (USC), during which time shediscovered a novel disease mechanism forcraniosynostosis, a birth defect that causesone or more sutures (borders where theskull’s bony plates intersect) on a baby'shead to close earlier than normal. Thisdiscovery led to the identification ofEphrin-A4 gene mutations in patientswith unassigned craniosynostosis.

In 2007, she completed a postdoctoralfellowship in Developmental Biology atthe University of California, SanFrancisco (UCSF) where she identified aunique potential of neural crest cells toautonomously control the timing of boneformation in the jaw using an avianchimeric system that draws upon thedivergent maturation rates of quail andduck embryos.

NEWFACULTY SPOTLIGHT

ONWARD AND UPWARDMeet Dr. AmyMerrill-Brugger, a promising addition to CCMB's faculty intent on further

advancing craniofacial biology through translational research.

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Dr. Merrill-Brugger then completed a post-doctoralfellowship in Medical Genetics in 2009 at CedarsSinai Medical Center where she established thelethal disorder, short-rib polydactyly syndrome, as aciliopathy by identifying mutations in themicrotubule motorDYNC2H1. Before shejoined CCMB in 2010, shealso completed a post-doctoral fellowship inHuman Genetics at theUniversity of California,Los Angeles (UCLA) whereshe focused on uncoveringthe disease mechanisms of1) Bent Bone Dysplasia, anewly classified skeletalbirth defect caused byabnormal FGFR2 signalingand 2) SpondylocarpotarsalSynostosis Syndrome, a progressive joint fusiondisorder resulting from mutations in FilaminB.The significance of being at CCMB working withworld-class leaders in Craniofacial MolecularBiology research is a fact that is not lost on Dr.Merrill-Brugger.

She highly touts CCMB’s nurturing environment,citing plentiful opportunities for interaction andcollaboration, both internal and external to CCMBand the University. She is currently working withDr. Pedro Sanchez, a clinician and geneticist with

Children’s Hospital, LosAngeles (CHLA) to uncoverthe genetic causes ofcraniofacial birth defects.Once they identify diseasegenes, she will define the roleof these genes during facialdevelopment.In addition to theopportunities forcollaboration, Dr. Merrill-Brugger cites the tremendoussupport that she continues toreceive from her colleagues at

CCMB and the University itself. "The facultycontinually lend insight into my work and provide ahuge support system that pushes me to be better. Idid my Ph.D. here in USC, so when I came onboard, it felt like coming home.”

“For what I do, studying craniofacialdevelopment, CCMB is one of thebest places in the world to be. It is atremendous honor to be part of agroup of clinicians and scientiststhat have inspired my workthroughout my career. To be a partof this organization is an amazingopportunity; one that I hope to liveup to."

“During embryonic development, thecraniofacial bones are formed by astepwise series of events that organizemesenchymal precursors of bone intoindividual skeletal elements with theproper shape and integration.Inherited human conditions thatinterrupt this process causedevastating birth defects withphysical and social obstacles. Bymerging techniques in humangenetics and developmental biology,my lab is uncovering mechanisms ofnormal and abnormal craniofacialdevelopment. Our research goal is toadvance molecular-based therapiesfor craniofacial bone regenerationand repair."

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When asked about her thoughts onher future in CCMB, Dr. Merrill-Brugger shared her optimism aboutthe eventual positive impact of herresearch and being a part ofCCMB’s future.

Being a researcher is not the onlyhat that Dr. Merrill-Brugger wears,as is the case for all CCMB facultymembers. She also teaches aproblem-based learning course forthe Ostrow School of Dentistry.Her teaching experience as a post-doctoral fellow at UCSF andUCLA has been invaluable inengaging a small group of dentalstudents who work through casestudies as part of the curriculum.In addition, she providesopportunities for interested dental

students to work in her laboratoryand believes that exposure toresearch is an important part oftheir experience.Currently, Dr. Merrill-Brugger isworking on distinguishing between

intracellular andextracellular FGF signalingin osteoprogenitor cellsduring craniofacialdevelopment, a projectsponsored by the March ofDimes Foundation whoawarded her with the BasilO’Connor Starter ScholarResearch Award in 2010.In addition, she is engagedin defining the nuclear

activities of FGFR2 during skeletaldevelopment which is a projectsponsored by the James H.Zumberge Research andInnovation Fund, USC’s ownuniversity-wide faculty researchgrant awarded to select new facultyto launch their research careers.She may only be in the infancy ofher career, but all signs pointtowards a highly distinguishedfuture for Dr. Merrill-Brugger andwith it a chance to further advance

the understanding of craniofacialdisorders. Perhaps her efforts willlead to viable therapies for birthdefects that can have such adevastating impact on the afflicted.CCMB is fortunate to have such apromising addition to its faculty;one that will support its mission tobuild on its strength as a world-class leader in craniofacialmolecular biology and help itsexpansion into translationalresearch.

“Research is of primary importanceto me. It is the area where I feel Ican make a big difference…it iswhere my heart is and being inCCMB provides the ideal place tostudy what I study. I want and hopeto be part of CCMB’s future and itsgrowth.”

As challenging as her schedule can be, Dr.Merrill-Brugger balances rigors of her workschedule with the demands of a youngfamily. She enjoys trips to the beach withher husband and 3-½ year old daughter, aswell as baking and yoga.

To find out more information about Dr.Merrill-Brugger, please visit CCMB's

website at www.usc.edu/hsc/dental/ccmb/34

Ruchi Bajpai, Ph.D.Assistant Professor

HermanOstrow School of Dentistry of USCKeck School ofMedicine of USC

Meet Dr. Ruchi Bajpai, another promising addition to CCMB's faculty whose deepappreciation for science and discovery fuels her fire to push the knowledge envelope.

Dr. Ruchi Bajpai's enthusiasm wascertainly abound when she discussedher research on early humandevelopment, specifically studyingbirth defects, pioneering thegeneration of human neural crests cells(NCC) from embryonic stem cells,and establishing methods todifferentiate and isolate human cellsrepresenting distinct facial domains.Dr. Bajpai joined CCMB in 2011 asone of two new faculty additions afteran exhaustive search involving 78applicants. Her research is gearedtowards revealing the molecular basisof craniofacial malformations. Dr.Bajpai aims to find innovative ways todiagnose, manage and/or eradicatecraniofacial birth defects powered byan understanding of the fundamentalconcepts of human development.Dr. Bajpai received her Ph.D. inDevelopmental Genetics in 2003 fromJawaherlal Nehru University in NewDelhi, India. She conducted researchin the Center for Cellular andMolecular Biology studying tiny fruitfly embryos in Dr. Rhashidhara’s labwhere she learned the basics of geneticanalysis and felt the compelling needto extend her studies to understandinghuman development.

NEWFACULTY SPOTLIGHT

THE JOY OF DISCOVERY

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During her postdoctoralfellowship at The BurnhamInstitute for MedicalResearch in La Jolla,California, she had theopportunity to initiate humanembryonic stem cell researchin Dr. Terskikh’s lab whereshe honed her skills incoaxing pluripotent cells intoa single, therapeuticallyrelevant, neural lineage until2006. Realizing that earlydevelopment is hugelyinfluenced by epigeneticmechanisms, Dr. Bajpai joined Dr. Wysocka’s lab atStanford University in 2007 to study chromatinremodeling which is a critical component of epigeneticregulation. In the Wysocka lab, she further refined stemcell differentiation into neural crest cells whilecombining biochemical and embryological methods inunderstanding congenital diseases. Dr. Bajpai’s researchhas resulted in two patents as a joint inventor for

Homogeneous NeuralPrecursor Cells (USPTOPub No. US20080254004)and Methods For Cultureand Production of SingleCell Populations ofHuman Embryonic StemCells (USPTO Pub No:US20080058221).For Dr. Bajpai, joiningCCMB and its illustriousfaculty has provided themeans for her to grow as ascientist in ways that shehad not considered before.

CCMB has provided Dr. Bajpai with the opportunity todirectly connect with patients through extensivecollaboration with researchers and clinicians alike. Dr.Pedro Sanchez of Children’s Hospital, Los Angeles(CHLA) and Dr. Mathew Lee of CCMB have helpedfurther stoke the fires that drive Dr. Bajpai to continueher journey to discovery.

"CCMB has provided me with theopportunity to go on to the next step. Inow have the opportunity to not onlylearn how certain diseases develop, butfind out what they really mean topatients. Having met children afflictedwith birth defects, I have designedpatient-oriented projects in my lab thatI would never have thought of beforecoming to CCMB.”

To find out more information about Dr.Bajpai, please visit CCMB's website at

www.usc.edu/hsc/dental/ccmb/

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Currently, the Bajpai lab isinterested in testing thetherapeutic potential of neuralcrest cells (NCC) derived fromhuman pluripotent stem cells(hPSC) that can serve as a sourcefor cell replacement therapy andas a model for studyingcraniofacial disease progression.Dr. Bajpai’s research focuses onunderstanding the molecularmechanisms regulating neuralcrest development using aninnovative combination ofmultidisciplinary methodology(combining hPSC differentiationwith cutting-edge epigenomic andchromatin biology approaches andin vivo embryological functionalassays). Their goal of in vivocharacterization of humanenhancers that drive expression insubsets of cranial neural crest(CNC) cells allows them to isolatedistinct craniofacial precursor cells,reveals gene regulatory mechanismsand their evolutionaryconservation, and serves as apowerful tool for genetic researchon craniofacial development.Additionally, Dr. Bajpai and herteam are utilizing thisdevelopmental information to gaininsight into the growth andmetastasis of neural crest relatedtumors like oral cancers and

neuroblastomas. Using lessonslearned from neural crests, theirattempts are focused on identifyingand characterizing tumor initiatingcells and metastatic cells that residewithin these extremelyheterogeneous tumors."Thinking of stem cells in atransient developmental state,arrested in a dish, has allowedus to gain in-depth molecularinsight into the dynamicprocesses occurring in anembryo. Now, that we havedeveloped unique researchtools, we are excited goingforward to learn how the face isformed”.As with all CCMB faculty, Dr.Bajpai is not just a researcher, but ateacher as well. She facilitatesproblem-based learning sessionsand lectures in stem cell courses, aswell as mentors trainees of all levelsfrom high school students to post-doctoral fellows for the Ostrow

School of Dentistry. Even thoughshe enjoys teaching and mentoring,the call of science is loudest to Dr.Bajpai. She states that she can peerinto the microscope for hours anddoes not cease to be fascinated byany developing embryos telling astory.

For one with such a passion forresearch, it is not surprising thatDr. Bajpai encourages others toshare her fascination with theprocess and the potential of itsresults. Dr. Bajpai expressed adesire to organize events sometimein the future that will attract moredental students to basic researchand let them see that it is possibleto incorporate it with clinicalpractice.Though only in the infancy of hercareer, Dr. Bajpai is already poisedto make an indelible mark incraniofacial development research.Her addition to CCMB only servesto preserve its status as an eliteresearch organization well into thefuture.

“I have to emphasize thatit was the joy of discoverythat got me into science;and then to realize thatwe have the power tomake a difference…itbecame a biggerresponsibility. Togetherthey are a driving force inmy life now.”

Dr. Bajpai shares her home with a verysupportive husband and two sons, ages 5 and 7.She draws inspiration from the excitement ofchildren with whom she voluntarily conductssmall science projects at her sons’ school when timepermits. She also opens her home to children in herneighborhood and enjoys painting with them inher backyard on weekends.

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Painted shoes depicting cellularchromatin control of a developing embryo

byMallory Holland

TeamFACULTYProfessorYang ChaiJanetMoradian-OldakMichael PaineSongtao ShiHarold SlavkinMalcolm SneadAssociate Clinical ProfessorStephen YenResearch AssociateProfessorMark UrataAssistant ProfessorRuchi BajpaiAmyMerrill-BruggerResearch AssistantProfessorMatthew LeeYan ZhouClinical Assistant ProfessorPedro Sanchez

ADMINISTRATIONSTAFFSr. Research AdministratorElsaMirandaSenior EditorBridget SamuelsBudget/Business AnalystZhounan LiuProject Specialist - AdministrativeVeronica ElizarrarasPatricia ThompsonProject Specialist - Administrative(CBY)Janice Bea

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CCMB ADMINISTRATIVE TEAMFrom left: Ed Vaynman, Pablo Bringas, Elsa Miranda, Jianbao Xie, MagdalenaMorales, Zhounan Liu, Bridget Samuels, Veronica Elizarraras, Pat Thompson

ADMINISTRATIONSTAFFAdministrative Assistant IIMagdalenaMoralesLaboratoryManagerPablo BringasEdward VaynmanClinical OfficeManager(Translational Research)Denise CortezSpecialized Laboratory TechnicianJianbao Xie

LABORATORY STAFFSr. Research AssociateJun-ichi IwataRodrigo Sosa LacruzResearch AssociateVictoria GallonZhanHuangAkiko SuzukiYanminWangXinWenHuZhaoPostdoctoral ResearchAssociateKarthki BalakrishnaChandrababuJifan FengArumHanJingyuan LiYi LiuSowmya Bekshe LokappaYudai Nishino

TeamLABORATORY STAFFPostdoctoral ResearchAssociateCarolina ParadaRichard PelikanQichao RuanSoma SamantaLeiWangYinghua ZhaoZhe ZhongResearch Lab SpecialistJianhua FanYa-Ping LeiSusan Smith

LABORATORY STAFFSpecialized LaboratoryTechnicianJulieMayoQingWangXingtian XuResearch Lab Technician III/SupervisorLisha ChenThach-VuHoResearch Lab Technician IIBrian IdoniShihong ShiResearch Lab Technician IShiyu LiuRuili Yang

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Team Building Events Celebrations

"Teamwork is the ability to work together toward a common vision. The ability tothat allows common people to attain uncommon results."

Events &Activities

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Gatherings Fun Camaraderie

direct individual accomplishments toward organizational objectives. It is the fuel

- Andrew Carnegie

Events &Activities

produced by Entheat Designsinfo@entheatdesigns.com

2012

Center for CraniofacialMolecular Biology2250 Alcazar StreetLos Angeles, CA 90033Mail Code: 9062Phone:(323)442-3170Fax: (323) 442-2981Web: www.usc.edu/hsc/dental/ccmb

Ostrow School of Dentistry of USCUniversity of Southern CaliforniaUniversity ParkLos Angeles, CA 90089-0641ostrow.usc.edu

CCMB - where innovative basic scienceresearch in craniofacial biology mergeswith cutting edge clinical practice.