Research in our laboratory is focused on understanding cellular and molecular mechanisms that regulate physiological and pathological bone metabolism, skeletal and craniofacial bone development and diseases.

Fei Liu, DDS, PhD

ABOUT

Research in our laboratory is focused on understanding cellular and molecular mechanisms that regulate physiological and pathological bone metabolism, skeletal and craniofacial bone development and diseases. In particular, we are interested in the following lines of research:

The roles of autophagy in skeletal and craniofacial bone metabolism: Autophagy is a conserved lysosomal degradation process that has important roles in both normal human physiology and disease. However, the function of autophagy in skeletal and craniofacial bone homeostasis is not well understood. We found that autophagy is activated during osteoblast differentiation. Ablation of FIP200 (focal adhesion kinase family interacting protein of 200 kD), an essential component of mammalian autophagy, leads to multiple autophagic defects in osteoblasts. Osteoblast-specific deletion of FIP200 leads to osteopenia in mice. Our current effort is to determine the molecular mechanisms and signaling pathways by which autophagy regulates mesenchymal stem cell, craniofacial osteogenic stem cell and osteoblast function using a combination of molecular, cell biological and mouse genetic approaches.

The regulation of skeletal and craniofacial bone development by mTOR signaling: Tuberous sclerosis (TS) is a genetic disorder characterized by the presence of benign congenital tumors in multiple organs and is caused by mutations in one of two genes, called TSC1 and TSC2. Tuberous sclerosing bone dysplasia is characterized by osteosclerotic changes in skeletal and craniofacial bones. In this disease, hyperactivity of mTOR (mammalian target of rapamycin) signaling is implicated. Despite the high frequency of osseous manifestation (>66%) in TSC patients, it is unknown to what extent and how mTOR signaling regulates bone metabolism in vivo. We established the first craniofacial sclerotic bone lesion mouse model of Tuberous sclerosis and found that enhanced mTOR signaling in neural crest-derived cells can increase bone mass through enlargement of the osteoprogenitor pool, which likely explains the sclerotic bone lesion observed in Tuberous sclerosis patients. We are currently using various genetic mouse models to elucidate the mechanisms by which mTOR signaling regulates skeletal and craniofacial bone development.

The regulation of bone development and health by FAK signaling: FAK (Focal adhesion kinase) is a major mediator of signal transduction by integrins. We recently demonstrated that FAK deletion in osteoblast progenitor cells leads to an osteopenia phenotype associated with increased bone marrow adiposity. The decreased bone mass in FAK-deficient mice is accounted for by decreased proliferation, compromised osteogenic differentiation, and increased adipogenic differentiation of bone marrow mesenchymal stromal/stem cells. Mechanistically, FAK deficiency leads to decreased Wnt/β-catenin signaling evidenced by lowered β-catenin protein levels and decreased mRNA expression of Wnt ligands and target genes. Our findings demonstrated that FAK plays an important role in bone mass acquisition and also identified a novel mechanism accountable for the negative correlation between bone mass and bone marrow adiposity. We are currently determining the function of FAK in mesenchymal stem cells and the impact of FAK inhibition on bone health.

DIRECTOR

Fei Liu, DDS, PhD

Associate Professor

Education and Training

BS/MS, Stomatology, West China University of Medical Sciences (Si Chuan University), Chengdu, China, 1996

DDS, West China University of Medical Sciences (Si Chuan University), Chengdu, China, 1999

PhD, Biomedical Science, University of Connecticut Health Center, Farmington, CT, 2006

Prosthodontic Certificate, University of Connecticut Health Center, Farmington, CT, 2006

Post-doc, University of Michigan, Ann Arbor, MI, 2006-2009

Board certification, American Board of Prosthodontics, 2009


Professional Membership and Service

2004 - present Member, American Society for Bone and Mineral Research
2007 - present Member, American Academy of Fixed Prosthodontics
2008 - 2013 Member, Tylman Research Committee of American Academy of Fixed Prosthodontics
2009 - present Member, International Chinese Musculoskeletal Research Society
2010 - present Fellow, American College of Prosthodontists
2012 - present Member, Research Committee, American College of Prosthodontists
2012 - 2014 Chair, Scientific Research Committee of American Academy of Fixed Prosthodontics
2013 - present Member, American Association of Dental Research
2013 - present Member, International Association of Dental Research
2013 - 2018 Chair, Tylman Research Committee of American Academy of Fixed Prosthodontics
2017 - 2020 Board Director, American Academy of Fixed Prosthodontics

Honors

1997 First place of Xuan Rui Ling dental graduate student scholarship, West China University of Medical Sciences (Si Chuan University)
1998 First place of DENTSPLY dental graduate student scholarship, West China University of Medical Sciences (Si Chuan University)
2004 Young Investigator Award, Advances in Skeletal Anabolic Agents for the Treatment of Osteoporosis (American Societyfor Bone and Mineral Research)
2004 ASBMR Young Investigator Award from American Society for Bone and Mineral Research
2004 First place of Remo Sinibaldi Memorial Table Clinic Competition, American College of Prosthodontics

Awards to Trainees

2013 Travel Award from American Society for Bone and Mineral Research to Dr. Fang Fang (post-doc fellow)
2015 Travel Award from American Society for Bone and Mineral Research to Dr. Li Wang (post-doc fellow)
2016 ASBMR Young Investigator Award from American Society for Bone and Mineral Research to Dr. Xiaoxi Wei (PhD student)
2016 Plenary oral presentation and ASBMR Young Investigator Award from American Society for Bone and Mineral Research to Dr. Chunhui Sun (visiting scholar)
2017 AADR student research fellowship to Neil Thomas (DDS candidate)
2017 Travel Award from American Society for Bone and Mineral Research to Dr. Han Kyoung Choi (post-doc fellow)

PUBLICATIONS

The most recent publications listed below.

View the complete list of publications

Postnatal Craniofacial Skeletal Development of Female C57BL/6NCrl Mice

2017; Frontier in physiology (Accepted); Wei, X | Thomas, N | Hatch, N | Hu, M | Liu, F

Male Germline Recombination of a Conditional Allele by the Widely Used Dermo1-Cre (Twist2-Cre) Transgene

2017; Genesis; He, Y | Sun, X | Wang, L | Mishina, Y | Guan, JL | Liu, F

TEAM

Li Wang, PhD

Research Fellow
lwa@umich.edu

Han Kyoung Choi, PhD

Research Fellow
Choihan@umich.edu

Xiaoxi Wei, BDS/MDS

PhD Student
Xiaoxiw@umich.edu

Neil Thomas, DDS candidate

Research Pathways Student
neilt@umich.edu

Yun He, DDS, PhD

Visiting Scholar
heyun@umich.edu

Guomin Wu, DDS, PhD

Visiting Scholar
guominw@umich.edu

Xiumei Sun, DDS, PhD

Visiting Scholar
xiumeis@umich.edu

Brannon Cavanaugh

UROP Research Scholar
bcava@umich.edu

CONTACT

Liu Lab
Department of Biologic and Materials Sciences and Division of Prosthodontics
University of Michigan School of Dentistry
1011 N University Ave,
Ann Arbor, MI 48109
Lab room#: 4214, 4228
Office room#: 4205
Lab phone#: 734-763-8532
Office phone#: 734-936-0911
Email: feiliu@umich.edu