Frank Beier

Genetics & Development Dr. Frank Beier
Scientist
Photo

Affiliations

Scientist, Division of Genetics and Development, Children’s Health Research Institute
Professor, Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry,
Western University
Director, Collaborative Graduate Program in Developmental Biology, Western University

How my research helps children

There are many different bone diseases that affect children. Some of these diseases are inherited, while others occur as a result of injuries, poor diet or specific medications. As a result of these diseases, patients might grow much slower than other children, or have a higher likelihood to break their bones, or suffer from specific deformities of their bones and joints that restrict movement. Most of our bones are formed as a cartilage model first, and this cartilage model also controls how fast our bones grow. Therefore, many bone diseases are actually due to problems that start in cartilage. My research group tries to understand the mechanisms that control the normal behavior of cartilage and how these mechanisms are changed in different diseases. By understanding these processes, we will be able to prevent and treat many types of bone and cartilage diseases affecting children.

Research

Current Research Activities

We are studying a number of signaling pathways controlling skeletal growth and development. These include:

  • Rho GTPases
  • Various kinases including PI3K/Akt, MAP and GSK3
  • Nuclear receptors such as the glucocorticoid receptor and RORalpha

In addition to these projects on skeletal development, we are also investigating molecular mechanisms mediating the destruction of joint cartilage in osteoarthritis, using surgical models in rats and mice in conjunction with genetic techniques and manipulations.

Research Team

I currently supervise or co-supervise two technicians, three postdoctoral fellows, ten graduate and four undergraduate students. Alumni from our lab have gone on to faculty positions and/or postdoctoral studies, or have entered Medical, Dental or Law School.

Future Research Plans

We will continue work on all the areas described above. In addition, we have recently started collaborating with Dr. Nathalie Bérubé on epigenetic regulators of skeletal development, a new project that forms an important part of our future plans.

Awards & Grants

Awards & Grants

Funding in support of Rac1 in skeletal development and homeostasis – Awarded by Canadian Institutes of Health Research (CIHR)

Funding in support of TGFalpha/EGFR signaling in osteoarthritis – Awarded by Canadian Institutes of Health Research (CIHR)

Funding in support of Glucocorticoid receptor and RORalpha in cartilage development and osteoarthritis – Awarded by Canadian Institutes of Health Research (CIHR)

Funding in support of Control of skeletal development by the chromatin remodeling protein ATRX – Awarded by Canadian Institutes of Health Research (CIHR), with Dr. Nathalie Bérubé, Western University

Funding in support of Rac1 function in endochondral ossification – Awarded by Canadian Institutes of Health Research (CIHR)

Recent Publications

Publications

Loss of ATRX does not confer susceptibility to osteoarthritis
Solomon LA, Russell B, Makar D, Berube NG, Beier F
PLoS ONE. 2013; 8:e85526

Role of Interleukin-10 in endochondral bone formation: Anabolic effect via BMP/Smad pathway
Jung Y-K, Kim G-W, Park H-R, Lee E-J, Choi J-Y, Beier B, Han S-W
Arthritis & Rheumatism. 2013; 65:3153-3164

ADAMTS-7 forms a positive feedback loop with TNF-a in the pathogenesis of osteoarthritis
Lai Y, Bai X, Zhao Y, Tian Q, Liu B, Lin EA, Chen Y, Lee B, Appleton CTG, Beier F, Yu X-P, Liu CJ
Ann Rheum Dis. 2013

GSK-3β function in bone regulates skeletal development, whole body metabolism and male life span
Gillespie JR, Bush JR, Bell GI, Aubrey LA, Dupuis H, Ferron M, Kream B, DiMattia G, Patel S, Woodett JR, Karsenty G, Hess D, Beier F
Endocrinology. 2013; 154:3703-3718

Targeted loss of the ATR-X syndrome protein in the limb mesenchyme of mice causes brachydactyly
Solomon LA, Russell B, Watson LA, Beier F, Berube NG
Hum Mol Genetics. 2013; 22:5015-5025

ATRX deficiency induces telomere dysfunction, endocrine defects, and reduced lifespan
Watson LA, Solomon LA, Li J, Jiang Y, Edwards M, Shin-ya K, Beier F, Bérubé NG
J Clin Invest. 2013; 123:2049-2063

Adult cartilage-specific peroxisome proliferator-activated receptor gamma knockout mice exhibit the spontaneous osteoarthritis phenotype
Vasheghani F, Monemdjou R, Fahmi H, Zhang Y, Perez G, Blati M, St-Arnaud R, Pelletier JP, Beier F, Martel-Pelletier J, Kapoor M
Am J Pathology. 2013; 182:1099-1106

Time-series transcriptional profiling yields new perspectives on susceptibility to murine osteoarthritis
Poulet B, Ulici V, Stone TC, Pead M, Gburcik V, Constantinou E, Palmer DB, Beier F, Timmons JA, Pitsillides AA
Arthritis & Rheumatism. 2012; 64:3256-3266

An in vivo investigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis
McErlain DD, Ulici V, Darling M, Gati JS, Pitelka V, Beier F, Holdsworth DW
Arthr Res Therapy. 2012; 14:R26

Association of cartilage-specific deletion of peroxisome proliferator-activated receptor γ with abnormal endochondral ossification and impaired cartilage growth and development in a murine model
Monemdjou R, Vasheghani F, Fahmi H, Perez G, Blati M, Taniguchi N, Lotz M, St-Arnaud R, Pelletier JP, Martel-Pelletier J, Beier F, Kapoor M
Arthritis & Rheumatism. 2012; 64:1551-1561
(note: Dr. Kapoor initiated these studies as a postdoctoral fellow in my laboratory, but performed most of the experiments after starting his own group).

Reduced chondrocyte proliferation, earlier cell cycle exit and increased apoptosis in neuronal nitric oxide synthase-deficient mice
Yan Q, Feng Q, Beier F
Osteoarthritis & Cartilage. 2012; 20:144-151

Gene expression profile in the articular cartilage of a natural model of osteoarthritis in the Str/ort mouse
Poulet B, Ulici V, Stone TC, Pead M, Gburcik V, Constantinou E, Palmer DB, Beier F, Timmons JA, Pitsillides AA
Arthritis & Rheumatism. 2012; 64:3256-3266

TGFalpha-deficient mice display transient delay in skeletal growth and resorption of hypertrophic cartilage
Usmani SE, Pest M, Kim GW, Ohora S, Qin L, Beier F
Bone. 2012; 51:131-141

Transforming growth factor alpha induces endothelin receptor A expression in osteoarthritis
Usmani SE, Appleton CTG, Beier F
J Orthop Res. 2012; 30:1391-1397

Initiation and progression of subchondral cysts in an in vivo, preclinical model of osteoarthritis
McErlain DD, Ulici V, Darling M, Gati JS, Pitelka V, Beier F, Holdsworth DW
Arthr Res Therapy. 2012; 14:R26

Association of cartilage-specific deletion of peroxisome proliferator-activated receptor γ with abnormal endochondral ossification and impaired cartilage growth and development in a murine model
Monemdjou R, Vasheghani F, Fahmi H, Perez G, Blati M, Taniguchi N, Lotz M, St-Arnaud R, Pelletier JP, Martel-Pelletier J, Beier F, Kapoor M
Arthritis & Rheumatism. 2012; 64:1551-1561
(note: Dr. Kapoor initiated these studies as a postdoctoral fellow in my laboratory, but performed most of the experiments after starting his own group).

Reduced chondrocyte proliferation, increased apoptosis and premature differentiation in neuronal nitric oxide synthase-deficient mice
Yan Q, Feng Q, Beier F
Osteoarthritis & Cartilage. 2012; 20:144-151

Emerging Frontiers in Cartilage and Chondrocyte Biology
Fosang AJ, Beier F
Best Practice and Research Clinical Rheumatology. 2011; 25:751-766

The critical role of the epidermal growth factor receptor (EGFR) in endochondral ossification
Zhang X, Siclari VA, Lan S, Zhu J, Koyama E, Dupuis HL, Enomoto-Iwamoto M, Beier F, Qin L
J Bone Miner Res. 2011; 26:2622-2633

Cartilage biology in osteoarthritis - lessons from developmental biology
Pitsillides AA, Beier F
Nature Reviews Rheumatology. 2011; 7:654-663

iNos and nitric oxide mediate mitogenic Rac1 signaling during endochondral bone development
Wang G, Yan Q, Woods A, Aubrey LA, Feng Q, Beier F
J Cell Science. 2011; 124:3405-3413

New insights in the pathobiology of cartilage degeneration: Implications for therapeutic interventions in osteoarthritis
LeBlanc EA, Beier F
US Musculoskeletal Review. 2011; 6:16-19

Deletion of Glycogen Synthase Kinase-3{beta} in Cartilage Results in Up-Regulation of Glycogen Synthase Kinase-3{alpha} Protein Expression
Gillespie JR, Ulici V, Dupuis H, Higgs A, DiMattia A, Patel S, Woodgett JR, Beier F
Endocrinology. 2011; 152:1755-1766

Rac1 activitation induces tumor necrosis factor-alpha expression and cardiac dysfunction in endotoxemia
Zhang T, Lu X, Beier F, Feng Q
J Cell Mol Medicine. 2011:15, 1109-1121

Endothelial nitric oxide synthase deficiency results in reduced chondrocyte proliferation and endochondral bone growth
Yan Q, Feng Q, Beier F
Arthritis Rheum. 2010 Mar 30. [Epub ahead of print]

PPARgamma2 expression in growth plate chondrocytes is regulated by p38 and GSK-3
Stanton LA, Li JR, Beier F
J Cell Mol Med. 2010 Jan; 14(1-2):242-56

Human stanniocalcin-1 or -2 expressed in mice reduces bone size and severely inhibits cranial intramembranous bone growth
Johnston J, Ramos-Valdes Y, Stanton LA, Ladhani S, Beier F, Dimattia GE
Transgenic Res. 2010 Feb 20

Regulation of gene expression by PI3K in mouse growth plate chondrocytes
Ulici V, James CG, Hoenselaar KD, Beier F
PLoS One. 2010 Jan 25; 5(1):e8866

Genome-wide analyses of gene expression during mouse endochondral ossification
James CG, Stanton LA, Agoston H, Ulici V, Underhill TM, Beier F
PLoS One. 2010 Jan 13; 5(1):e8693.

Rho/ROCK and MEK/ERK activation by transforming growth factor-alpha induces articular cartilage degradation
Appleton CT, Usmani SE, Mort JS, Beier F
Lab Invest. 2010 Jan; 90(1):20-30.

Additional publications

Contact

Contact

Phone: (5190 661-2111, x85344
Fax: (519) 661-3827
Email: fbeier [at] uwo [dot] ca
Website: http://www.uwo.ca/physpharm/beier/

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