Discover CCMB 2022

CENTER FOR CRANIOFACIAL MOLECULAR BIOLOGY

Hello!

PHOTOS - LEFT TO RIGHT/ CHAI LAB (3), CHEN LAB, PAINE LAB, LIN LAB, XU LAB, CCMB SYMPOSIUM

CONTACT US

Phone: (323) 442 -3170

Fax: (323) 442-2981

ccmb.usc.edu

2250 Alcazar Street

CSA 103 Los Angeles, CA 90033

(Mail Code: 9062)

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TABLE OF CONTENTS

Welcome to CCMB

Research Focus + Collaborations

About CCMB + Meet Our Team

CCMB 2030 Strategic Plan

Director's Message

Meet Our Faculty

Meet Our Laboratory Team

Yang Chai, DDS, PhD

Jianfu Chen, PhD

Dechen Lin, PhD

Zhaoyang Liu, PhD

Amy Merrill, PhD

Janet Moradian-Oldak, PhD

Michael Paine, BDS, PhD

Malcolm Snead, DDS, PhD

Jian Xu, PhD

Events & Activities

Welcome to Center for Craniofacial

“

CCMB IS FOREMOST A COLLABORATIVE ENVIRONMENT. THERE IS EXTENSIVE INTERACTION AMONG THE FACULTY WITH EACH GROUP HAVING ITS OWN AREA OF EXPERTISE. IT IS SUCH A FUN AND HAPPY PLACE TO WORK IN; YOU ONLY HAVE TO LOOK AT OUR FACULTY AND SEE HOW SUPPORTIVE THEY ARE OF EACH OTHER. MANY PEOPLE, INCLUDING MYSELF, FEEL THAT CCMB HAS SUCH GREAT POTENTIAL. WE WILL CONTINUE TO EXPAND OUR RESEARCH, ATTRACT PROMISING SCIENTISTS AND BE THE ENVY OF THE CRANIOFACIAL RESEARCH COMMUNITY.”

YANG CHAI, DDS, PHD DIRECTOR

to the Craniofacial Biology

Research Collaborations

About CCMB

The Center for Craniofacial Molecular Biology (CCMB) is the Ostrow School of Dentistry's primary research facility; located in the heart of the University of Southern California's Health Sciences Campus

CCMB is home to a diverse group of world-class researchers in a variety of disciplines centered around structures of the craniofacial region. Since its establishment in 1989, CCMB has been home to several major discoveries and has attracted top researchers from around the world. CCMB also serves as a bridge that connects Medicine and Dentistry, allowing meaningful and productive collaborations to exist between the Keck School of Medicine and the Ostrow School of Dentistry.

CCMB receives its funding from numerous federal and organization-sponsored research grants, many of which originate from the National Institute of Dental

and Craniofacial Research (NIDCR) under which basic research is conducted into developmental, biochemical, molecular and biological aspects of human development, with special emphasis on craniofacial structures in both health and disease.

In addition to highly-acclaimed researchers, CCMB is also comprised of top-notch graduate students, post-doctoral fellows, research technicians and administrators who work together effectively to fulfill the center's mission to advance oral, dental and craniofacial research toward solving problems in health and promoting the well being of society.

FOR MORE INFORMATION

Meet Our Team

PROJECT SPECIALISTADMINISTRATIVE

BUDGET/BUSINESS ANALYST

SENIOR RESEARCH ADMINISTRATOR

BRIDGET SAMUELS, PHD

PROJECT DIRECTOR

JANICE BEA

LINDA HATTEMER EXECUTIVE ASSISTANT TO THE DIRECTOR

THACH-VU HO, MS, EDS

INSTRUCTIONAL LABORATORY MANAGER

ZHOUNAN LIU

GISELLE MEJIA PUBLIC COMMUNICATIONS COORDINATOR

GINA NIETO

ASSISTANT RESEARCH ADMINISTRATOR

TAC PHUNG

JIAN-BAO XIE

LABORATORY TECHNICIAN

CCMB 2030 Strategic

Our vision for CCMB in 2030 is built on a foundation with four strong pillars:

ATTRACT, RETAIN, & SUPPORT HIGH-CALIBER FACULTY

We recognize that our ability to advance the frontier of science and train the next generation of craniofacial researchers depends crucially on cultivating a faculty with diverse interests and expertise. We will continue to recruit researchers who share our commitment to improving craniofacial health and whose research programs demonstrate potential for attracting funding and producing high-quality publications. In support of our trajectory of growth, we will strive to provide an excellent environment for conducting research, with laboratory space, shared equipment, and support staff necessary for these efforts. We will continue to provide pilot funding to enable our faculty to generate preliminary data and support their personnel as they transition to other mechanisms of support.

ENABLE INNOVATIVE RESEARCH DIRECTIONS TO IMPROVE HUMAN HEALTH

As the craniofacial community fully realizes the potential of recent revolutionary scientific advances such as the burgeoning “omics” fields and nanotechnology, we envision that many new avenues of research will become integral to improving health care. Though the full spectrum of future developments cannot be foreseen, we have identified a number of areas of increasing importance, in which CCMB can and should bolster our capabilities: (i) cell-based and regenerative medicine; (ii) the microbiome; (iii) genomics; (iv) nanotechnology-guided material science; and (v) clinical trials and novel therapies. In addition to our existing strengths in bone, tooth, brain, cartilage and neural crest biology, we have identified further tissues of interest including nerves, muscles, and salivary glands.

Strategic Plan

TRAIN & MENTOR THE LEADING SCIENTISTS & CLINICIANS OF TOMORROW

As one of the nation’s premier research centers in craniofacial biology, we have a strong impetus to do our part to ensure that the future of the field is bright. We believe that the clinical and scientific workforce of the future must be diverse and interdisciplinary, and that as consumers of scientific literature, they are best served by engaging in hands-on research experience. We affirm our commitment to recruiting and fostering an inclusive community of researchers from diverse backgrounds, including those which are underrepresented in science. We will provide a supportive environment for our students and early-career scholars that provides intellectually and personally enriching activities, including comprehensive mentorship from more senior researchers throughout USC and beyond as well as opportunities for professional development. To these ends, we will offer research opportunities for high school, undergraduate, and postgraduate students; and encourage our junior researchers to compete for early-career awards.

EMPOWER THE BROADER COMMUNITY THROUGH OUTREACH & COMMUNICATION

We believe that the knowledge gained through our scientific efforts is meant to be shared, and that it is our responsibility to promote transparency and reproducibility in research. Furthermore, we aim to increase our visibility in the Los Angeles area and beyond, in order to inform, educate, and empower the public to take control of their health. In addition to making our research findings available through scientific publications and publically available data repositories, we will also communicate with other stakeholders through press releases, social media, publications geared towards those outside our field, and government advocacy. Through the appropriate conduits in the development office, we will also establish connections with philanthropists in order to gain support for our innovative research and training program.

Director's Message

Welcome to the Center for Craniofacial Molecular Biology (CCMB) at the Herman Ostrow School of Dentistry at the University of Southern California.

CCMB is a research laboratory located on the USC Health Sciences Campus. USC is proud to be a member of a small group of elite research universities in the nation. CCMB is a worldrenowned research center where innovative basic science research in craniofacial biology merges with cutting-edge clinical practice. The laboratory is funded through numerous federal and organization-sponsored research grants. Many of these grants are from the National Institute of Dental and Craniofacial Research, under which fundamental and translational research is conducted into developmental, biochemical and molecular biological aspects of human development, with

a special emphasis on craniofacial structures in both health and disease. Specifically, our faculty members are conducting research on diverse topics including (1) the molecular genetics of tooth development; (2) the cellular and molecular etiology of craniofacial birth defects including cleft palate and craniosynostosis; (3) enamel matrix formation and biomineralization; (4) transcriptional control of craniofacial development; (5) stem cell-mediated craniofacial tissue regeneration; (6) upper aerodigestive cancer; (7) human skeletal diseases; (8) neurodevelopment and neurodegeneration; as well as many others.

History has shown that the public derives immeasurable benefits from investment in biomedical research in a wide array of health areas. Looking to the future of dental, oral, and craniofacial research, it is clear that CCMB

“WORKING TOGETHER, WE ARE ADVANCING ORAL, DENTAL, AND CRANIOFACIAL RESEARCH TOWARD SOLVING PROBLEMS IN HEALTH AND PROMOTING THE WELL-BEING OF SOCIETY.

YANG CHAI, DDS, PHD DIRECTOR

will continue to make a strong impact in these areas. As we conduct groundbreaking research and train the future leaders of our profession, we will continue to emphasize the importance of oral health and how it affects the rest of the body. We will work closely with our colleagues to translate scientific discovery to practical health care. We will explore diverse funding sources to support our research. We will make every effort to train the next generation of scientists who will continue to create new knowledge to benefit society. We will continue to advance scientific knowledge and promote innovation so that our society can reap the rewards in the form of healthier lives.

I invite you to explore many of the exciting

research projects conducted at CCMB and discover how our faculty, staff, and students are working together to shape the future of health care.

Sincerely,

Yang Chai, DDS, PhD

University Professor

George & Marylou Boone Chair in Craniofacial Molecular Biology

Associate Dean of Research Director, Center for Craniofacial Molecular Biology

Herman Ostrow School of Dentistry University of Southern California

(PHOTO/ BOBAK HA'ERI)

Meet our Faculty

UNIVERSITY PROFESSOR

George & MaryLou Boone Chair in Craniofacial Biology, Herman Ostrow School of Dentistry of USC

UNIVERSITY PROFESSOR

Stem Cell Biology & Regenerative Medicine, Keck School of Medicine of USC

JIANFU CHEN, PHD

DIRECTOR

Craniofacial Biology Graduate Program, Herman Ostrow School of Dentistry of USC

DECHEN LIN, PHD

YANG CHAI, DDS, PHD ASSISTANT PROFESSORASSOCIATE PROFESSORDIRECTOR

ASSOCIATE DEAN OF RESEARCH

Herman Ostrow School of Dentistry of USC

MICHAEL PAINE, BDS, PHD

PROFESSOR

MALCOLM SNEAD, DDS, PHD PROFESSOR

ZHAOYANG LIU, PHD

JANET MORADIAN-OLDAK, MSC, PHDAMY MERRILL, PHD

PROFESSORASSOCIATE PROFESSORASSISTANT PROFESSOR

CHAIR

Department of Biomedical Sciences, Herman Ostrow School of Dentistry of USC

ASSOCIATE PROFESSOR

Keck School of Medicine of USC

PROFESSOR OF BIOMEDICAL SCIENCES & BIOENGINEERING

USC Viterbi School of Engineering

JIAN XU, PHD

ASSOCIATE PROFESSOR

YAN ZHOU, PHD

ASSOCIATE PROFESSOR OF RESEARCH

STEPHEN YEN, DMD, PHD

ASSOCIATE PROFESSOR (CLINICAL SCHOLAR)

Meet Our Laboratory Team

MST NAHID AKHTER

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

JESSE ANDERSON RESEARCH LAB TECHNICIAN II

RUCHA BAPAT

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

ERIKA B. NOWOTNY

RESEARCH ASSISTANT

LAUREN GRADUATE

ISHMAEL HOWARD

RESEARCH LAB TECHNICIAN II

EVA JANECKOVA

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

SUPAWADEE JARIYASAKULROJ

GRADUATE STUDENT

YANBIN JI

RESEARCH ASSOCIATE

JUNJUN

POSTDOCTORAL RESEARCH

JINGTAN SU

RESEARCH ASSOCIATE

GAYATHRI VISAKAN RESEARCH ASSISTANT

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

JIAN-BAO XIE

SPECIALIZED LABORATORY TECHNICIAN

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

JIANG RESEARCH ASSISTANT

TAKAHIKO YAMADA

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

CHEHYUN NAM

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

AUDREY NICKLE

GRADUATE STUDENT

SIDDHIKA PAREEK

FEI PEI

MINGYI ZHANG

POSTDOCTORAL RESEARCH

BOBZIN

STUDENT

JING CAI

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

JIFAN FENG

RESEARCH ASSOCIATE

TINGWEI GUO

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

THACH-VU HO

INSTRUCTIONAL LABORATORY MANAGER

JUNJUN JING

POSTDOCTORAL SCHOLARASSOCIATE

NATALIE KEGULIAN

RESEARCH ASSOCIATE

BIN BIN LI

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

MENGMENG LIU

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

LI MA

POSTDOC FELLOWFELLOWSHIP TRAINEE

QIAN ASSISTANT

RESEARCH LAB TECHNICIAN II

RESEARCH LAB TECHNICIAN II

ZHANG

POSTDOCTORAL SCHOLARASSOCIATE

WEI ZHANG

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

MEHRNAZ ZARINFAR

GRADUATE STUDENT

HUA ZHAO

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

BENJAMIN ZIMAN

POSTDOCTORAL SCHOLARRESEARCH ASSOCIATE

JOTHAM SADAN

JANET SANCHEZ

PRERNA SEHGAL RESEARCH ASSISTANT

ANDRES STUCKY RESEARCH ASSOCIATE

DIRECTOR

YANG CHAI DDS, PHD

University Professor George & MaryLou Boone Chair in Craniofacial Biology Director

Center for Craniofacial Molecular Biology

Associate Dean of Research

Herman Ostrow School of Dentistry of USC University Professor

Stem Cell Biology & Regenerative Medicine

Keck School of Medicine of USC

CHAILAB.USC.EDU

Dr. Chai earned a DMD degree from Peking University School of Stomatology as well as a DDS degree and PhD in Craniofacial Biology from USC. He is most noted for his re search on craniofacial development and birth defects, which has transformed the field and is advancing our understanding of the molecular and cellular mechanism of craniofacial mal formations. He also studies stem cells and is using innovative 3D-printed scaffolds seeded with stem cells to regenerate tissue for patients with craniofacial defects due to trauma, con genital malformations, or diseases. Dr. Chai is an elected member of the National Academy of Medicine. He is also an elected fellow of the American Academy of Arts and Sciences. Dr. Chai has authored more than 160 scientific papers and numerous book chapters, as well as edited a book on craniofacial development. Dr. Chai has been continuously funded by the National Institutes of Health for more than 25 years. His work has earned him multiple awards including the 2011 International Association of Dental Research Distinguished Scientist Award.

PHOTO COURTESY OF CHAI LAB

CURRENT FUNDING

Molecular Regulatory Mechanism of Mesenchymal Stem Cells in Adult Mouse Incisors

•

Principal Investigator: Yang Chai

•

Sponsor: National Institute of Dental & Craniofacial Research (R01)

•

The goal of this project to provide important knowledge of the signaling network that regulates the transition from MSCs to TA cells in maintaining tissue homeostasis and will serve as the foundation for future studies in MSC biology and stem cell-mediated tissue regeneration.

Molecular Regulatory Mechanism of Tooth Root Development

•

Principal Investigator: Yang Chai

•

Sponsor: National Institute of Dental & Craniofacial Research (R01)

•

The major goal of this project is to test the hypothesis that BMP-mediated SHH, WNT and FGF signaling and the epigenetic modulator Ezh2 control the fate of epithelial and mesenchymal stem cells during root development.

Center for Dental, Oral and Craniofacial Tissue and Organ Regeneration (C-DOCTOR)

•

Principal Investigator: Yang Chai

• Sponsor: National Institute of Dental & Craniofacial Research (U24)

•

The goal of this project to provide important knowledge of the signaling network that regulates the transition from MSCs to TA cells in maintaining tissue homeostasis and will serve as the foundation for future studies in MSC biology and stem cell-mediated tissue regeneration.

Mechanisms and rescue of craniosynostosis associated with gene-environment interaction

•

Principal Investigator: Jianfu Chen & Yang Chai

• Sponsor: National Institute of Dental & Craniofacial Research (R01)

• The major goal of this project is to improve our understanding of gene-environment interaction in craniosynostosis and guide our therapeutic efforts in MSC-mediated tissue regeneration in treating craniosynostosis.

USC FaceBase III Craniofacial Development and Dysmorphology Data Management and Integration Hub

• Principal Investigator: Carl Kesselman & Yang Chai

•

Sponsor: National Institute of Dental & Craniofacial Research (U01)

• The major goal of the FaceBase Consortium is to advance research by creating comprehensive datasets of craniofacial development and dysmorphologies, and to disseminate these datasets to the wider craniofacial research community.

TGF-β Signaling and Craniofacial Morphogenesis

•

Principal Investigator: Yang Chai

•

Sponsor: National Institute of Dental & Craniofacial Research (R01)

•

The goal of this project is to understand the molecular and cellular mechanism that is critical for regulating palatal fusion during craniofacial morphogenesis.

PUBLICATIONS

1. Stanton E, Urata M, Chen JF, Chai Y. (2022) The clinical manifestations, molecular mechanisms, and treatment of craniosynostosis. Dis Model Mech. 2022 Apr 1;15(4):dmm049390. doi: 10.1242/dmm.049390. Epub 2022 Apr 22. PMID: 35451466; PMCID: PMC9044212.

2. Guo T, Han X, He J, Feng J, Jing J, Janeckova E, Lei J, Ho T-V, Xu J, Chai Y. (2022) KDM6B interacts with TFDP1 to activate P53 signalling in regulating mouse palatogenesis. eLife. 2022 Feb 25;11:e74595. doi: 10.7554/eLife.74595. PMID: 35212626; PMCID: PMC9007587.

3. Ting MC, Farmer DT, Teng CS, He J, Chai Y, Crump JG, Maxson RE. (2022) Embryonic requirements for Tcf12 in the development of the mouse coronal suture. Development. 2022 Jan 1;149(1):dev199575.

4. Lei J, Chen S, Jing J, Guo T, Feng J, Ho TV, Chai Y. (2022) Inhibiting Hh signaling in Gli1+ osteogenic progenitors alleviates TMJOA. J Dent Res. 2022 Jan 20;220345211059079.

5. Ma L, Wang J, Ge J, Wang Y, Zhang W, Du Y, Luo J, Li Y, Wang F, Fan G, Chen R, Yao B, Zhao Z, Guo ML, Kim WK, Chai Y, Chen JF. (2021) Reversing neural circuit and behavior deficit in mice exposed to maternal inflammation by Zika virus. EMBO Rep. 2021 Aug 4;22(8):e51978.

6. Du J, Jing J, Chen S, Yuan Y, Feng J, Ho TV, Sehgal P, Xu J, Jiang X, Chai Y. (2021) Arid1a regulates cell cycle exit of transitamplifying cells through inhibiting the Aurka-Cdk1 axis in mouse incisor. Development. 2021 Apr 15;148(8):dev198838.

7. Du J, Jing J, Yuan Y, Feng J, Han X, Chen S, Li X, Peng W, Xu J, Ho TV, Jiang X, Chai Y. (2021) Arid1a-Plagl1-Hh signaling is indispensable for differentiation-associated cell cycle arrest of tooth root progenitors. Cell Rep. 2021 Apr 6;35(1):108964.

8. Johnson ZM, Yuan Y, Li X, Jashashvili T, Jamieson M, Urata M, Chen Y, Chai Y. (2021) Mesenchymal stem cells and threedimensional-osteoconductive scaffold regenerate calvarial bone in critical size defects in swine. Stem Cells Transl Med. 2021 Aug;10(8):1170-1183.

9. Han X, Feng J, Guo T, Loh YE, Yuan Y, Ho TV, Cho CK, Li J, Jing J, Janeckova E, He J, Pei F, Bi J, Song B, Chai Y. (2021) Runx2-Twist1 interaction coordinates cranial neural crest guidance of soft palate myogenesis. eLife. 2021 Jan 22;10:e62387.

10. He J, Jing J, Feng J, Han X, Yuan Y, Guo T, Pei F, Ma Y, Cho C, Ho TV, Chai Y. (2021) Lhx6 regulates canonical Wnt signaling to control the fate of mesenchymal progenitor cells during mouse molar root patterning. PLoS Genet. 2021 Feb 17;17(2):e1009320.

11. Yu M, Ma L, Yuan Y, Ye X, Montagne A, He J, Ho TV, Wu Y, Zhao Z, Sta Maria N, Jacobs R, Urata M, Wang H, Zlokovic BV, Chen JF, Chai Y. (2021) Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis. Cell. 2021 Jan 7;184(1):243-256.e18.

12. Jing J, Feng J, Li J, Zhao H, Ho TV, He J, Yuan Y, Guo T, Du J, Urata M, Sharpe P, Chai Y. (2021) Reciprocal interaction between mesenchymal stem cells and transit amplifying cells regulates tissue homeostasis. eLife. 2021 Jan22;10:e59459.

PHOTOS COURTESY OF CHAI LAB

ASSOCIATE PROFESSOR

JIANFU CHEN PHD

Director

Craniofacial Biology Graduate Program

Herman Ostrow School of Dentistry of USC

CHENLAB.USC.EDU

Dr. Chen earned his Ph.D. in Cell & Developmental Biology from the University of North Carolina at Chapel Hill. The Chen laboratory studies brain development and neu rodegenerative disorders such as dementia as well as craniofacial neuroscience. The lab uses genetically modified mice alongside human pluripotent stem cells and brain organoids to model neurological and craniofacial disorders followed by mechanistic studies on the molec ular, cellular, circuit, and behavioral levels. One unique aspect of the lab’s work is integrating Dr. Chen’s neuroscience background with cranio facial research strengths at USC to investigate the interface of the neural and skeletal sys tems, including brain-skull crosstalk, stem cell regulation and regenerative medicine, as well as craniofacial innervation and pain, with the aim of translating these discoveries into the development of new therapeutic strategies for treating neurological and craniofacial diseases.

CURRENT FUNDING

Genetic analysis of a microRNA pathway regulating neural tube closure

• Principal Investigator: Jianfu Chen

• Sponsor: National Institute of Neural Disorders & Stroke (R01)

• The goal of this project is to improve our understanding of genetic factors associated with neural tube defects and provide novel insights into mechanisms underlying neural tube closure and neural tube defects.

Neurovascular functions of a small RNA Snord118-mediated ribosome biogenesis

• Principal Investigator: Jianfu Chen

• Sponsor: National Institute on Aging (R21)

• The goal of this project is to establish new genetically modified mice to model small vessel diseases and to investigates the function of ribosome biogenesis in neurovascular cells.

Mechanisms and rescue of craniosynostosis associated with gene-environment interaction

• Principal Investigator: Jianfu Chen & Yang Chai

• Sponsor: National Institute of Dental & Craniofacial Research (R01)

• The major goal of this project will improve our understanding of gene-environment interaction in craniosynostosis and guide our therapeutic efforts in MSC-mediated tissue regeneration in treating craniosynostosis.

Mechanisms regulating neural progenitor expansion in the developing brain

• Principal Investigator: Jianfu Chen

• Sponsor: National Institute of Dental & Craniofacial Research (R01)

• The goal of this project is to improve our understanding of mitosis and cell cycle re-entry regulation of neural progenitor cells in the developing brain and provide novel insights into mechanisms underlying human microcephaly diseases.

(PHOTO/ WEI ZHANG)

PUBLICATIONS

1. Stanton E, Urata M, Chen JF, Chai Y. (2022) The clinical manifestations, molecular mechanisms, and treatment of craniosynostosis. Dis Model Mech. 2022 Apr 1;15(4):dmm049390. doi: 10.1242/dmm.049390. Epub 2022 Apr 22. PMID: 35451466; PMCID: PMC9044212.

2. Ma L, Wang J, Ge J, Wang Y, Zhang W, Du Y, Luo J, Li Y, Wang F, Fan G, Chen R, Yao B, Zhao Z, Guo ML, Kim WK, Chai Y, Chen JF. (2021) Reversing neural circuit and behavior deficit in mice exposed to maternal inflammation by Zika virus. EMBO Rep. 2021 Aug 4;22(8):e51978.Ting MC, Farmer DT, Teng CS, He J, Chai Y, Crump JG, Maxson RE. (2022) Embryonic requirements for Tcf12 in the development of the mouse coronal suture. Development. 2022 Jan 1;149(1):dev199575.

3. Wu Y, Wu H, Zeng J, Pluimer B, Dong S, Xie X, Guo X, Ge T, Liang X, Feng S, Yan Y, Chen JF, Sta Maria N, Ma Q, Gomez-Pinilla F, Zhao Z. (2021) Mild traumatic brain injury induces microvascular injury and accelerates Alzheimer-like pathogenesis in mice. Acta Neuropathol Commun. 2021 Apr 23;9(1):74.

4. Yu M, Ma L, Yuan Y, Ye X, Montagne A, He J, Ho TV, Wu Y, Zhao Z, Sta Maria N, Jacobs R, Urata M, Wang H, Zlokovic BV, Chen JF, Chai Y. (2021) Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis. Cell. 2021 Jan 7;184(1):243-256Du J, Jing J, Chen S, Yuan Y, Feng J, Ho TV, Sehgal P, Xu J, Jiang X, Chai Y. (2021) Arid1a regulates cell cycle exit of transit-amplifying cells through inhibiting the Aurka-Cdk1 axis in mouse incisor. Development. 2021 Apr 15;148(8):dev198838.

5. Zhang M, Li K, Bai J, Velema WA, Yu C, van Damme R, Lee WH, Corpuz ML, Chen JF, Lu Z. (2021) Optimized photochemistry enables efficient analysis of dynamic RNA structuromes and interactomes in genetic and infectious diseases. Nat Commun. 2021 Apr 20;12(1):2344.

6. 6. Zeng J, Dong S, Luo Z, Xie X, Fu B, Li P, Liu C, Yang X, Chen Y, Wang X, Liu Z, Wu J, Yan Y, Wang F, Chen JF, Zhang J, Long G, Goldman SA, Li S, Zhao Z, Liang Q. (2020) The Zika Virus Capsid Disrupts Corticogenesis by Suppressing Dicer Activity and miRNA Biogenesis. Cell Stem Cell. 2020 Oct 1;27(4):618-632.e9.

7. Zhang W, Ma L, Yang M, Shao Q, Xu J, Lu Z, Zhao Z, Chen R, Chai Y, Chen JF. (2020) Cerebral organoid and mouse models reveal a RAB39b-PI3K-mTOR pathway-dependent dysregulation of cortical development leading to macrocephaly/autism phenotypes. Genes Dev. 2020 Apr 1;34(7-8):580-597. doi: 10.1101/gad.332494.119.

8. Shao Q, Yang M, Liang C, Ma L, Zhang W, Jiang Z, Luo J, Lee JK, Liang C, Chen JF. (2020) C9orf72 and smcr8 mutant mice reveal MTORC1 activation due to impaired lysosomal degradation and exocytosis. Autophagy. 2020 Sep;16(9):1635-1650.

ASSISTANT PROFESSOR

DECHEN LIN PHD

SITES.USC.EDU/LINLAB

Dr. Lin obtained his PhD degree in Cell Biology at the Chinese Academy of Medical Sciences, Tsinghua University, China, in 2010. Subsequently, he was a postdoctoral fellow at Cedars-Sinai Medical Center, UCLA School of Medicine, and the National University of Singapore, focusing on cancer genomics. He was promoted to Research Scientist Faculty and started a laboratory at Cedars-Sinai Medical Center, UCLA School of Medicine in 2016. He joined CCMB as a tenure-track Assistant Professor in 2022, directing an NCI-funded laboratory, with the focus on investigating genomic and epigenomic abnormalities in upper aerodi gestive cancer, including head and neck as well as esophageal cancers. Lin laboratory has developed strong research expertise in these cancer types, and established model systems, innovative methodologies as well as patient biobanks. Dr. Lin was among the first in the world to demonstrate the genomic landscape of esophageal cancer and head and neck cancer. He delineated for the first time the clonal evolution of esophageal can cer, and his work on enhancer de-regulation has opened a new frontier of research for this malignancy. Additionally, he has de veloped novel mathematical methods and computational pipelines for the analyses of genomic and epigenomic data.

CURRENT FUNDING

Master regulator transcription factors promote esophageal neoplastic evolution

• Principal Investigator: Dechen Lin

•

Sponsor: National Cancer Institute (R37)

• The goal of this project is to establish primary driving forces of Barrett’s esophagus-associated neoplasia evolution and uncover epigenomic mechanisms underlying esophagus transformation, which will fundamentally transform our insights into the biology of esophageal cancer.

PUBLICATIONS

1. Dinh H.Q, Pan F, Wang G, Q Huang, C Olingy, Z Wu, S Wang, X Xu, X Xu, J He, Q Yang, S Orsulic, M Haro, L Li, G Huang, J Breunig, H Koeffler, C Hedrick, L Xu, Lin DC, E Li. (2021) Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment. Nat Commun. 2021 Dec 17;12(1):7335.

2. Ho AS, Robinson A, Shon W, Laury A, Raedschelders K, Venkatraman V, Holewinski R, Zhang Y, Shiao SL, Chen MM, MallenSt Clair J, Lin DC, Zumsteg ZS, Van Eyk JE. (2021) Comparative Proteomic Analysis of HPV(+) Oropharyngeal Squamous Cell Carcinoma Recurrence. J Proteome Res. 2021 Nov 30.

3. Ho AS, Luu M, Shafqat I, Mallen-St Clair J, Chen MM, Chen Y, Jain M, Ali N, Patio C, Filarski CF, Lin DC, Bankston H, Braunstein GD, Sacks WL, Zumsteg ZS. (2021) Predictive Impact of Metastatic Lymph Node Burden on Distant Metastasis Across Papillary Thyroid Cancer Variants. Thyroid. 2021 Oct;31(10):1549-1557.

4. Lin DC. (2021) A closer look at esophageal cancer through different lenses. EBioMedicine. 2021 Sep;71:103545.

5. Li LY, Yang Q, Jiang YY, Yang W, Jiang Y, Li X, Hazawa M, Zhou B, Huang GW, Xu XE, Gery S, Zhang Y, Ding LW, Ho AS, Zumsteg ZS, Wang MR, Fullwood MJ, Freedland SJ, Meltzer SJ, Xu LY, Li EM, Koeffler HP, Lin DC. (2021) Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer. Nat Commun. 2021 Jul 16;12(1):4362.

6. Zheng Y, Huang G, Silva TC, Yang Q, Jiang YY, Koeffler HP, Lin DC, Berman BP. (2021) A pan-cancer analysis of CpG Island gene regulation reveals extensive plasticity within Polycomb target genes. Nat Commun. 2021 Apr 30;12(1):2485.

7. Lin DC. (2021) Exercise impacts the epigenome of cancer. Prostate Cancer Prostatic Dis. 2021 May 27.

8. Jiang Y, Jiang YY, Lin DC. (2021) Super-enhancer-mediated core regulatory circuitry in human cancer. Comput Struct Biotechnol J. 2021 May 5;19:2790-2795.

9. Ho AS, Luu M, Kim S, Tighiouart M, Mita AC, Scher KS, Mallen-St Clair J, Walgama ES, Lin DC, Nguyen AT, Zumsteg ZS. (2021) Nodal staging convergence for HPV-and HPV+ oropharyngeal carcinoma. Cancer. 2021 May 15;127(10):1590-1597.

10. 1Guo Z, Pan F, Peng L, Tian S, Jiao J, Liao L, Lu C, Zhai G, Wu Z, Dong H, Xu X, Wu J, Chen P, Bai X, Lin D, Xu L, Li E, Zhang K. (2021) Systematic Proteome and Lysine Succinylome Analysis Reveals the Enhanced Cell Migration by Hyposuccinylation in Esophageal Squamous Cell Cancer. Mol Cell Proteomics. 2021 Feb 6;20:100053.

11. Ma S, Zhou B, Yang Q, Pan Y, Yang W, Freedland SJ, Ding LW, Freeman MR, Breunig JJ, Bhowmick NA, Pan J, Koeffler HP, Lin DC. (2021) A Transcriptional Regulatory Loop of Master Regulator Transcription Factors, PPARG, and Fatty Acid Synthesis Promotes Esophageal Adenocarcinoma. Cancer Res. 2021 Mar 1;81(5):1216-1229.

ASSISTANT PROFESSOR

ZHAOYANG LIU PHD

Dr. Liu received her bachelor’s degree from Nanjing Agricultural University in 2008 and her PhD from the University of Rochester in 2014. She completed her postdoctoral research at The University of Texas at Austin from 2016 to 2022. Dr. Liu is interested in understanding molecular etiology of joint disorders, such as osteo arthritis and cartilaginous tissue degener ation. Her research has identified several molecules and signaling pathways regulating knee joint and intervertebral disc develop ment and homeostasis.

CURRENT FUNDING

Analyzing the role of cAMP and STAT3 signaling in cartilage homeostasis and osteoarthritis development

• Principal Investigator: Zhaoyang Liu

• Sponsor: National Institute of Arthritis & Musculoskeletal & Skin Diseases (K99/R00)

• This project seeks to generate new mechanistic understanding of distinct signaling pathways and determine whether manipulation of these pathways can protect against osteoarthritis progression in mouse models.

Mapping the gene regulation of post-traumatic osteoarthritis and cAMP signaling of the knee joint

• Principal Investigator: Zhaoyang Liu

• Sponsor: American Society for Bone and Mineral Research

• The goal of this project is to map the gene regulation and signaling mechanisms active in the knee joint in the setting of post-traumatic arthritis.

PUBLICATIONS

1. Liu Z, Hussien AA, Wang Y, Heckmann T, Gonzalez R, Karner CM, Snedeker JG, Gray RS. An adhesion G protein-coupled receptor is required in cartilaginous and dense connective tissues to maintain spine alignment. eLife. 2021;10.

2. Makki N, Zhao J, Liu Z, Eckalbar WL, Ushiki A, Khanshour AM, Wu J, Rios J, Gray RS, Wise CA, Ahituv N. Genomic characterization of the adolescent idiopathic scoliosis-associated transcriptome and regulome. Hum Mol Genet. 2021;29(22):3606-15.

3. Liu Z, Easson GWD, Zhao J, Makki N, Ahituv N, Hilton MJ, Tang SY, Gray RS. Dysregulation of STAT3 signaling is associated with endplate-oriented herniations of the intervertebral disc in Adgrg6 mutant mice. PLoS Genet. 2019;15(10):e1008096.

4. Liu Z, Ramachandran J, Vokes SA, Gray RS. Regulation of terminal hypertrophic chondrocyte differentiation in Prmt5 mutant mice modeling infantile idiopathic scoliosis. Dis Model Mech. 2019;12(12). (Cover Article)

5. Ramachandran J *, Liu Z *, Gray RS, Vokes SA. PRMT5 is necessary to form distinct cartilage identities in the knee and long bone. Dev Biol. 2019;456(2):154-63.

6. Zheng Y, Liu C, Ni L, Liu Z, Mirando AJ, Lin J, Saijilafu, Chen D, Hilton MJ, Li B, Chen J. Cell type-specific effects of Notch signaling activation on intervertebral discs: Implications for intervertebral disc degeneration. J Cell Physiol. 2018;233(7):5431-40.

ASSOCIATE PROFESSOR

AMY MERRILL PHD

Chair

Department of Biomedical Sciences

Herman Ostrow School of Dentistry of USC

Associate Professor

Keck School of Medicine of USC

MERRILL.USC.EDU

D

r. Merrill’s research program bridges clinical and basic sciences to study congenital conditions that impact development of the skeletal system. Dr. Merrill earned her Ph.D. in Biochemistry and Molecular Biology in 2005 from USC and went on to complete postdoctoral fel lowships in Developmental Biology at the University of California, San Francisco and Medical Genetics at Cedars-Sinai Medical Center and UCLA. The goal of Dr. Merrill’s independent research program is to un derstand congenital skeletal disorders for which little is known and, in the process, gain a deeper understanding of skeletal development. One of her most significant contributions to date has been the discovery of the lethal genetic syndrome Bent Bone Dysplasia (MIM 614591). Her research has identified the causal gene mutations for Bent Bone Dysplasia in Fibroblast Growth Factor Receptor 2 and revealed mechanistic insights into disease etiology using patient-specif ic cells and animal models. Dr. Merrill has

pioneered prenatal diagnosis for Bent Bone Dysplasia and demonstrated that a path way key to the pathophysiology of a large number of congenital skeletal differences directly regulates protein synthesis. In 2019, Dr. Merrill was awarded the Marylou Buyse Excellence in Craniofacial Research Award from the Society for Craniofacial Genetics and Developmental Biology and currently serves as the society’s Vice President. The success of her trainees is her top priority. Her trainees’ research accomplishments include NIH diversity fellowships, a F31 NIH Predoctoral fellowship, highly covet ed positions on USC’s T32 and T90 institu tional NIH training grants, a USC Provost’s Graduate Student Scholarship, a USC’s Roy E. Thomas Scholarships, USC’s Order of the Torch, speaking invitations at national meetings, award recognition from national societies, and multiple first-author publica tions. In 2022, she was the recipient of the USC Mentoring Award for Faculty Mentoring Graduate Students.

CURRENT FUNDING

Developmental regulation of tendon-bone connectivity in the jaw

• Principal Investigator: Amy Merrill

• Sponsor: National Institute of Dental & Craniofacial Research (R01)

• The major goal of this project is to identify the fundamental steps that regulate development of tendon-bone attachments in the mammalian jaw.

Modular control of jaw tendon specification by the Nr5a2 orphan nuclear receptor

• Principal Investigator: Amy Merrill

• Sponsor: National Institute of Dental & Craniofacial Research (R21)

• The goals of this grant are to understand the molecular mechanisms by which tendon fate is specified in different parts of the body, with an emphasis on the role of Nr5a2 in promoting jaw tendons.

PUBLICATIONS

1. Farmer DT, Mlcochova H, Zhou Y, Koelling N, Wang G, Ashley N, Bugacov H, Chen HJ, Parvez R, Tseng KC, Merrill AE, Maxson RE Jr, Wilkie AOM, Crump JG, Twigg SRF. (2021) The developing mouse coronal suture at single-cell resolution. Nat Commun. 2021 Aug 10;12(1):4797.

2. Bobzin L, Roberts RR, Chen HJ, Crump JG, Merrill AE. (2021) Development and maintenance of tendons and ligaments. Development. 2021 Apr 15;148(8):dev186916.

3. Roberts RR, Bobzin L, Teng CS, Pal D, Tuzon CT, Schweitzer R, Merrill AE. (2019) FGF signaling patterns cell fate at the interface between tendon and bone. Development. 2019 Aug 2;146(15). pii: dev170241.

4. Tuzon CT, Rigueur D, Merrill AE. (2019) Nuclear Fibroblast Growth Factor Receptor Signaling in Skeletal Development and Disease. Curr Osteoporos Rep. 2019 Jun;17(3):138-146.

5. Salva JE, Roberts RR, Stucky TS, Merrill AE. (2019) Nuclear FGFR2 regulates musculoskeletal integration within the developing limb. Dev Dyn. 2019 Mar;248(3):233-246.

6. Rigueur D, Roberts RR, Bobzin L, Merrill AE. (2019) A requirement for Fgfr2 in middle ear development. Genesis. 2019 Jan;57(1):e23252.

(PHOTO/ RYAN ROBERTS)

JANET MORADIANOLDAK MSC, PHD

Professor

Herman Ostrow School of Dentistry of USC Professor of Biomedical Sciences & Bioengineering

USC Viterbi School of Engineering

OLDAKLAB.USC.EDU

Dr. Moradian-Oldak completed her BSc degree in Chemistry in 1984 at the Ben Gurion University, a master’s degree in Structural Chemistry in 1986, and a PhD de gree in 1992 from the Department of Structural Biology at the Weizmann Institute of Science, Israel. She has published more than 120 articles in peer-reviewed journals and book chapters. Her main research goal is to understand the principles that govern the formation and min eralization of dental enamel by learning how the intricate matrix of proteins, enzymes and minerals come together to form this remark able bioceramic. The ultimate goal is to help scientists develop new dental materials that more closely mimic the structure and function of natural tooth enamel. Her areas of research that are currently funded by R01 grants from NIH-NIDCR integrate physical chemistry, bio chemistry, molecular biology, biotechnology, and biomaterial sciences in the study of min eralization of tooth enamel. Among various awards, she was the recipient of the 2015 GSK IADR Innovation in Oral Care Award and 2019

IADR Distinguished Scientist award, and in 2019 was elected as a Fellow of the AAAS.

PHOTO COURTESY OF JANET OLDAK LAB

CURRENT FUNDING

Monetite-Apatite Phase Transformation for an Enamel-Like Restorative Material

• Principal Investigator: Janet Moradian-Oldak

• Sponsor: National Institute of Dental & Craniofacial Research (R21)

• The major goal of this exploratory/developmental research proposal is to explore a novel biomimetic calcium phosphate (CaP) composite material that will have an enamel-like structure and can be applied to restore posterior Class I cavities.

A Peptide-Based Biomineralization Strategy for Tooth Repair

• Principal Investigator: Janet Moradian-Oldak

• Sponsor: National Institute of Dental & Craniofacial Research (R01)

• The goal of this proposal is to advance our understanding of ameloblastin’s structure and function through a systematic investigation of its interactions with different targets. The longterm goal is to understand the general principles that apply to the formation of dental enamel and to develop biomimetic strategies for the fabrication of enamel-like materials in vitro

PUBLICATIONS

1. Shao C, Bapat RA, Su J, Moradian-Oldak J. (2022) Regulation of Hydroxyapatite Nucleation In Vitro through AmeloblastinAmelogenin Interactions. ACS Biomater Sci Eng. 2022 Jan 24.

2. Visakan G, Su J, Moradian-Oldak J. (2022) Ameloblastin promotes polarization of ameloblast cell lines in a 3-D cell culture system. Matrix Biol. 2022 Jan;105:72-86.

3. Moradian-Oldak J, George A. (2021) Biomineralization of Enamel and Dentin Mediated by Matrix Proteins. J Dent Res. 2021 Sep;100(10):1020-1029.

4. Mukherjee K, Chakraborty A, Sandhu G, Naim S, Bauza Nowotny E, Moradian-Oldak J. (2021) Amelogenin Peptide-Chitosan Hydrogel for Biomimetic Enamel Regrowth. Front. Dent. Med. 2:697544.

5. Bapat RA, Su J, Moradian-Oldak J. (2020) Co-Immunoprecipitation Reveals Interactions Between Amelogenin and Ameloblastin via Their Self-Assembly Domains. Front Physiol. 2020 Dec 23;11:622086.

6. Su J, Bapat RA, Visakan G, Moradian-Oldak J. (2020) An Evolutionarily Conserved Helix Mediates Ameloblastin-Cell Interaction. J Dent Res. 2020 Aug;99(9):1072-1081.

7. Mukherjee K, Visakan G, Phark JH, Moradian-Oldak J. (2020) Enhancing Collagen Mineralization with Amelogenin Peptide: Towards the Restoration of Dentin. ACS Biomater Sci Eng. 2020 Apr 13;6(4):2251-2262.

PHOTO COURTESY OF JANET OLDAK LAB

PROFESSOR

MICHAEL PAINE BDS, PHD

PAINELAB.USC.EDU

Dr. Paine obtained both his dental degree (BDS) and PhD from Sydney University, Australia and then post-doctoral training at the University of Southern California. He completed further clinical training in Periodontology at USC, and in 1998 became a faculty member as an Assistant Professor. He was promoted to full Professor with tenure in 2011. His research interests include understanding the molecular biology and physiology of the cellular events that result in the for mation of enamel. Currently funded pro jects in the Paine Lab are investigating ion transport mechanisms at the apical pole of enamel-forming ameloblasts cells, and pH regulation of the mineralizing enamel. Dr. Paine also is the PI on a NIH/NIDCR training grant that supports several PhD students and post-docs both in Ostrow, and Keck.

(PHOTO/ SARAH TUGGY)

CURRENT FUNDING

Amelogenesis and Ion Transport

• Principal Investigator: Michael Paine

• Sponsor: National Institute of Dental & Craniofacial Research (R01)

•

The major goal of this grant is to better define the cellular activities that define the maturationstage of amelogenesis include calcium, bicarbonate, chloride, proton and phosphate transport, and the strict control of intracellular and extracellular pH. This project seeks to understand cellular activities that regulate and maintain an enamel extracellular matrix pH conducive to enamel mineralization.

Doctoral and Post-doctoral Training in Craniofacial Biology

• Principal Investigator: Michael Paine

• Sponsor: National Institute of Dental & Craniofacial Research (T90/R90)

• These R90 and T90 grants support education and training for a select cadre of graduate students and post-doctoral scholars with a major focus on dental, orofacial and craniofacial health-related disease processes.

CRE Mouse Models to Study Amelogenesis

• Principal Investigator: Michael Paine

• Sponsor: National Institute of Dental & Craniofacial Research (UH3)

• In the UG3 phase of this award, two knock-in mutant mouse lines were generated, Ambn-IRESCre and Odam-IRESCre, where expression is limited to secretory ameloblasts and maturation-stage ameloblasts, respectively. The goal during this UH3 funding period is to examine a series of floxed mutant mice with these novel Cre mouse lines.

PUBLICATIONS

1. Shao C, Bapat RA, Su J, Moradian-Oldak J. (2022) Regulation of Hydroxyapatite Nucleation In Vitro through AmeloblastinAmelogenin Interactions. ACS Biomater Sci Eng. 2022 Jan 24.

2. Visakan G, Su J, Moradian-Oldak J. (2022) Ameloblastin promotes polarization of ameloblast cell lines in a 3-D cell culture system. Matrix Biol. 2022 Jan;105:72-86.

3. Moradian-Oldak J, George A. (2021) Biomineralization of Enamel and Dentin Mediated by Matrix Proteins. J Dent Res. 2021 Sep;100(10):1020-1029.

4. Mukherjee K, Chakraborty A, Sandhu G, Naim S, Bauza Nowotny E, Moradian-Oldak J. (2021) Amelogenin Peptide-Chitosan Hydrogel for Biomimetic Enamel Regrowth. Front. Dent. Med. 2:697544.

5. Bapat RA, Su J, Moradian-Oldak J. (2020) Co-Immunoprecipitation Reveals Interactions Between Amelogenin and Ameloblastin via Their Self-Assembly Domains. Front Physiol. 2020 Dec 23;11:622086.

6. Su J, Bapat RA, Visakan G, Moradian-Oldak J. (2020) An Evolutionarily Conserved Helix Mediates Ameloblastin-Cell Interaction. J Dent Res. 2020 Aug;99(9):1072-1081.

7. Mukherjee K, Visakan G, Phark JH, Moradian-Oldak J. (2020) Enhancing Collagen Mineralization with Amelogenin Peptide: Towards the Restoration of Dentin. ACS Biomater Sci Eng. 2020 Apr 13;6(4):2251-2262.

PROFESSOR

MALCOLM SNEAD DDS, PHD

Dr. Snead received a baccalaureate in chemistry and biology along with the Lasallian core values from the Christian Brothers of St. Mary’s College of California and his DDS degree from the Chicago College of Dental Surgery, Loyola University of Chicago. At the University of Chicago he accomplished his residency train ing in oral pathology, oral radiology and oral medicine at the Zoller Dental Clinic where he also earned a doctoral degree in pathology and taught medical students at the Pritzker School of Medicine. He moved to USC and stayed for the next four decades where he has been involved in medical education, practicing diagnostic dental medicine and performing biomedical science since the first genes were cloned, the first stem cells isolated and the human genome decod ed. Snead is interested in developmental biology and the molecular continuations between altered developmental pathways and the emergence of disease states. For two decades, he served as an ad hoc and chartered member of several NIH study

section panels before joining the Advisory Council of the National Institute for Dental and Craniofacial Research. He is among the cadre of creators for the Problem-Based Learning program at the Ostrow, with ser vice as the School’s Associate Dean for Innovation and Discovery and most recently as the Chair of Biomedical Sciences. At the University level he served on the Provost’s Advisory Panel for Research Advancement, as the Co-Chair of the Academic Leadership Committee, as a member, then the Chair of the University Committee on Academic Probation and Tenure with the institution's last five provosts and on the University Committee on Academic Review since its inception. He received a doctorate honoris causa from the University of Oslo. He is an elected fellow of the American Association of the Advancement of Science and the American Institute for Medical and Biological Engineering. He is attempting to translate knowledge from basic research to devices that improve patient care and outcomes.

CURRENT FUNDING

Supramolecular nanofibers for recombinant growth factor-free spine fusion

• Principal Investigator: Malcolm Snead

• Sponsor: National Institute of Arthritis & Musculoskeletal & Skin Diseases (R01)

• The goal of this project is to develop a highly effective strategy to regenerate bone using recombinant growth factor-free bioactive nanoscale materials, suitable to spine fusion and other orthopaedic applications. The nanofiber scaffold developed in this work will be used either on its own or in combination with bone marrow stromal cells rather than with recombinant growth factor. Such an approach could obviate the need for recombinant factors, thereby providing a safer and more effective therapeutic strategy for bone regeneration in spinal fusion and other orthopaedic applications.

PUBLICATIONS

1. Woolfolk SK, Cloyd AK, Ye Q, Boone K, Spencer P, Snead ML, Tamerler C. (2022) Peptide-Enabled Nanocomposites Offer Biomimetic Reconstruction of Silver Diamine Fluoride-Treated Dental Tissues. Polymers (Basel). 2022 Mar 28;14(7):1368. doi:10.3390/polym14071368. PMID: 35406242; PMCID: PMC9002525.

2. Geng S, Lei Y, Snead ML. (2021) Minimal amelogenin domain for enamel formation. JOM. 2021 Jun;73(6):1696-1704.

3. Ruspita I, Das P, Xia Y, Kelangi S, Miyoshi K, Noma T, Snead ML, D’Souza RN, Bei M. (2020) An Msx2-Sp6-Follistatin Pathway Operates During Late Stages of Tooth Development to Control Amelogenesis. Front Physiol. 2020 Oct 26;11:582610.

4. Wisdom EC, Zhou Y, Chen C, Tamerler C, Snead ML. (2020) Mitigation of peri-implantitis by rational design of bifunctional peptides with antimicrobial properties. ACS Biomater Sci Eng. 2020 May 11;6(5):2682-2695.

5. Wisdom C, Chen C, Yuca E, Zhou Y, Tamerler C, Snead ML. (2019) Repeatedly Applied Peptide Film Kills Bacteria on Dental Implants. JOM. 2019 Apr;71(4):1271-1280.

6. Nirvani M, Khuu C, Tulek A, Utheim TP, Sand LP, Snead ML, Sehic A. (2019) Transcriptomic analysis of MicroRNA expression in enamel-producing cells. Gene. 2019 Mar 10;688:193-203.

PHOTO COURTESY OF MALCOLM SNEAD LAB

ASSOCIATE PROFESSOR

JIAN XU PHD

XULAB.USC.EDU

Dr.Xu received her B.S. degree from Peking University in 2000 and obtained her Ph.D. from the University of Cincinnati in 2006 under the mentorship of Dr. Jeff Molkentin, then continued with postdoctoral training in Dr. Rik Derynck’s group at the University of California, San Francisco. She joined USC in November 2013 and set up her independent research group at the Center for Craniofacial Molecular Biology. Her group is interested in the molecular mech anism by which protein methylation regulates signal transduction and cell fate determination, with a specific focus on craniofacial and cardiac development and injury repair.

CURRENT FUNDING

Modulation of Runx2 by arginine methylation

• Principal Investigator: Jian Xu

• Sponsor: National Institute of Dental & Craniofacial Research (R21)

• The major goal of this project is to improve the understanding of bone development, homeostasis and regeneration, and provide novel therapeutic approaches to tackle skeletal disorders.

Methylation signaling in periodontal health and disease

• Principal Investigator: Jian Xu

• Sponsor: National Institute of Dental & Craniofacial Research (R01)

• The goal of this project is to investigate the roles of Smad6 methylation in the signaling crosstalk between TGF-beta and TLR-NFkB pathways and periodontal inflammatory responses.

Protein methylation pathways that control genetic susceptibility to environmental pollutants in the occurrence of craniofacial defects

• Principal Investigator: Jian Xu

• Sponsor: National Institute of Dental & Craniofacial Research (R01)

• The major goal of this project is to dissect genetic and environmental mechanisms regulating craniofacial tissue morphogenesis and stress responses.

(PHOTO/ JOHN SKALICKY)

PUBLICATIONS

1. Guo T, Han X, He J, Feng J, Jing J, Janečková E, Lei J, Ho TV, Xu J, Chai Y. (2022) KDM6B interacts with TFDP1 to activate P53 signaling in regulating mouse palatogenesis. eLife. 2022 Feb 25;11:e74595.

2. Xu J, Richard S. (2021) Cellular pathways influenced by protein arginine methylation: Implications for cancer. Mol Cell. 2021 Nov 4;81(21):4357-4368.

3. Qin J, Xu J. (2021) Arginine methylation in the epithelial-to-mesenchymal transition. FEBS J. 2021 Aug 6.

4. Du J, Jing J, Chen S, Yuan Y, Feng J, Ho TV, Sehgal P, Xu J, Jiang X, Chai Y. (2021) Arid1a regulates cell cycle exit of transitamplifying cells through inhibiting the Aurka-Cdk1 axis in mouse incisor. Development. 2021 Apr 15;148(8):dev198838.

5. Du J, Jing J, Yuan Y, Feng J, Han X, Chen S, Li X, Peng W, Xu J, Ho TV, Jiang X, Chai Y. (2021) Arid1a-Plagl1-Hh signaling is indispensable for differentiation-associated cell cycle arrest of tooth root progenitors. Cell Rep. 2021 Apr 6;35(1):108964.

6. Wu J, Chen X, Sehgal P, Zhang T, Jackson-Weaver O, Gou Y, Bautch V, Frenkel B, Sun H, Xu J. (2021) Arginine methylation of R81 in Smad6 confines BMP-induced Smad1 signaling. J Biol Chem. 2021 Mar 2;296:100496.

7. Fan Z, He L, Li M, Cao R, Deng M, Ping F, Liang X, He Y, Wu T, Tao X, Xu J, Cheng B, Xia J. (2020) Targeting methyltransferase PRMT5 retards the carcinogenesis and metastasis of HNSCC via epigenetically inhibiting Twist1 transcription. Neoplasia. 2020 Nov;22(11):617-629.

8. Jackson-Weaver O, Ungvijanpunya N, Yuan Y, Qian J, Gou Y, Wu J, Shen H, Chen Y, Li M, Richard S, Chai Y, Sucov HM, Xu J. (2020) PRMT1-p53 Pathway Controls Epicardial EMT and Invasion. Cell Rep. 2020 Jun 9;31(10):107739.

9. Zhang W, Ma L, Yang M, Shao Q, Xu J, Lu Z, Zhao Z, Chen R, Chai Y, Chen JF. (2020) Cerebral organoid and mouse models reveal a RAB39b-PI3K-mTOR pathway-dependent dysregulation of cortical development leading to macrocephaly/autism phenotypes. Genes Dev. 2020 Apr 1;34(7-8):580-597.

PHOTO COURTESY OF JIAN XU LAB

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