Sumner Lab

PI:  D. Rick Sumner, Ph.D., Professor and Chair

Major research focus
Methods of enhancing bone regeneration for improving fixation of orthopedic implants (e.g. for joint replacement) are being investigated in experimental models. These studies emphasize the use of growth factors and biomimetic surfaces in models of primary and revision arthroplasty.  Bone adaptation to altered mechanical stresses, especially as it relates to osteoarthritis, is also being studied.

Major techniques
The Sumner lab’s major piece of equipment is a micro computed tomography scanner, which forms a key element in one of Rush’s research cores [link to:  http://www.rush.edu/rumc/page-1209563821067.html].  In addition, the laboratory performs undecalcified hard tissue histology and has expertise in morphometric and densitometric analyses.

Personnel

Current research support (as PI or Co-PI)
NIH R21 AR054171 (“Development and Initial Application of a Rat Model for Revision Joint Replacement”)
NIH R44 AR051264 (“Improved Orthopedic Implant Surface Coatings”)
T32 AR052272 (“Training in Orthopedic Skeletal Biology”)
Amgen 200716350 (“Use of anti-sclerostin antibody to enhance intramembranous bone formation and implant fixation in the rat”)

Selected recent manuscripts of interest

• Barber TA, Ho J, De Ranieri A, Virdi AS, Sumner DR, Healy KE: Peri-implant bone formation and implant integration strength of peptide-modified p(AAm-co-EG/AAc) IPN coated titanium implants.  J Biomed Mater Res 80A:306-320, 2007
• Sumner DR, Turner TM, Urban RM, Virdi AS, Inoue N: Additive enhancement of implant fixation following combined treatment with rhTGF-ß2 and rhBMP-2 in a canine model.  Journal of Bone and Joint Surgery (Am) 88:806-817, 2006
• Thorp LE, Wimmer MA, Block JA, Moisio KC, Shott S, Goker B, Sumner DR: Bone mineral density in the proximal tibia varies as a function of static alignment and knee adduction angular momentum in individuals with medial knee osteoarthritis.  Bone 39:1116-1122, 2006
• De Ranieri A, Virdi AS, Kuroda S, Shott S, Dai Y, Sumner DR: Local application of rhTGF- ß 2 modulates dynamic gene expression in a rat implant model.  Bone 36:931-940, 2005
• Kuroda S, Virdi AS, Dai Y, Shott S, Sumner DR: Patterns and localization of gene expression during intramembranous bone regeneration in the rat femoral marrow ablation model.  Calcif Tissue Int  77:212-225, 2005

Sena Lab

PI:  Kotaro Sena, D.D.S., Ph.D., Assistant Professor

Research interests
The laboratory focuses on musculoskeletal and dental tissue.  Currently, the laboratory is interested in relation between bone and vasculature which is regulated by multiple factors.  The studies provide better understanding between bone and vasculature and advance research toward novel therapeutics in impaired bone repair where angiogenesis is inhibited.  In addition, mechanisms for bone diseases are also being studied.

Major techniques
To elucidate the relation between bone and vasculature, cellular biology and molecular biology approach are used.  Specifically, in vitro; cell culture, gene expression (realtime PCR), protein production and in vivo studies are performed in the lab.  Immunohistochemistry (immunofluorescence) and in situ hybridization are also used in the lab.
Dr. Sena, together with Mr. Karwo, runs Histology laboratory in the department, which forms a key element in one of Rush’s research cores [link to:  http://www.rush.edu/rumc/page-1209563821067.html].  The laboratory performs soft tissue and decalcified hard tissue histology.

Personnel

Current research support (as PI)
Rush University Committee on Research (UCR) Grant: “Growth Differentiation Factor-5 (GDF-5) Regulated Angiogenesis in Bone.”

Manuscripts of interest

• Sena K, Sumner DR, Virdi AS. Modulation of VEGF expression in rat bone marrow stromal cells by GDF-5. Connect Tissue Res 48(6):324-331, 2007.
• Chung EH, Gilbert M, Virdi AS, Sena K, Sumner DR, Healy KE. Biomimetic Artificial ECMs Stimulate Bone Regeneration. J Biomed Mater Res A 79:815-26, 2006.
• Sena K, Leven RM, Mazhar K, Sumner DR, Virdi AS. Early Gene Response to Low-Intensity Pulsed Ultrasound in Rat Osteoblastic Cells. Ultrasound Med Biol 31:703-8, 2005.
• Sena K, Morotome Y, Baba O, Terashima T, Takano Y, Ishikawa I. Gene Expression of Growth Differentiation Factors in the Developing Periodontium of Rat Molars. J Dent Res 82:166-71, 2003.

Virdi Lab

PI:  Amarjit S. Virdi, Ph.D., Assistant Professor

Major research focus
The biology of the bone cell in bone repair and regeneration is being investigated at the tissue, cellular and molecular levels in both in vitro and in vivo models. In particular, the response of cells to biochemical (bone morphogenetic protein-2) and/or mechanical (low intensity pulsed ultrasound) stimuli is being studied to refine protocols for potential clinical applications. Additionally, trafficking of endogenous Mesenchymal Stem Cells during bone repair is being investigated. These projects complement the research interests of Dr. Sumner’s lab.

Major techniques
A number of small animal models of bone regeneration are being employed to study the biological responses to applied stimuli. Cell responses are being studied in in vitro cell culture systems. Gene expression is being analyzed using microarray and real time PCR approaches.

Personnel

Current research support (as PI or Co-I)

1. Baxter Healthcare (Bone healing in the rat calvarial defect using fibrin glue and growth factors)
2. NIH R21 AR054171 (“Development and Initial Application of a Rat Model for Revision Joint Replacement”)
3. NIH R44 AR051264 (“Improved Orthopedic Implant Surface Coatings”)
4. T32 AR052272 (“Training in Orthopedic Skeletal Biology”)
5. Amgen 200716350 (“Use of anti-sclerostin antibody to enhance intramembranous bone formation and implant fixation in the rat”)

Selected recent manuscripts of interest

• Pylawka, T.K., Virdi, A.S., Cole, B.J. and Williams, J.M. (2008) Reversal of suppressed metabolism in prolonged cold preserved cartilage. J Orthop Res. 26(2):247-54.
• Sena. K., Sumner, D.R. and Virdi, A.S. (2007) Modulation of VEGF expression in rat bone marrow stromal cells by GDF-5. Connect Tissue Res. 48(6):324-31.
• Sumner, D.R., Turner, T.M., Urban, R.M., Virdi, A.S. and Inoue, N. (2006) Additive Enhancement of Implant Fixation Following Combined Treatment with rhTGF-β2 and rhBMP-2 in a Canine Model. J Bone Joint Surg 88-A:806-817.
• Kuroda, S., Virdi, A.S., Dai Y., Shott, S. and Sumner, D.R. (2005) Patterns and localization of Gene Expression During Intramembranous Bone Regeneration in the Rat Femoral Marrow Ablation Model. Calcif Tissue Int 77:1-15.
• Sena, K., Leven, R.M., Mazhar, K., Sumner, D.R. and Virdi, A.S. (2005) Early Gene Response to Low-intensity Pulsed Ultrasound Exposure in Rat Bone Marrow Derived Osteoblastic Cells. J Ultrasound Med 31: 703-708.
• Virdi, A.S., De Ranieri, A., Kuroda, S., Dai, Y. and Sumner, D.R. (2004) Anabolic agents and gene expression around the bone implant interface. J Musculoskeletal Neuronal Interactions 4:388-389.

Zheng Lab

PI:  Qiping Zheng, M.D., Ph.D., Assistant Professor at Department of Anatomy and Cell Biology, Rush University Medical Center

Research Focus
Currently, the laboratory focuses on following research projects:

1. Identification of transcriptional determinants that regulate Col10a1 expression during endochondral bone formation;
   
2. Characterization of the correlations between altered chondrocyte maturation and diseased progression in skeletal dysplasias and osteoarthritis;
   
3. Functional study of Runx2 during bone development and cancer formation using novel mouse models generated in the lab.  

Chondrocyte hypertrophy/maturation is the terminal stage of chondrocyte differentiation linking both cartilage and bone development.  It’s a well coordinated process that involves multiple signaling pathways during chondrocyte degradation, mineralization, apoptosis and angiogenesis.  Understanding the molecular mechanisms regulating chondrocyte maturation will lead to identification of novel molecuular targets that could be used for therapeutic intervention and treatment of skeletal disorders and bone related cancers.

 
Major Techniques
To perform functional studies of genes of interest, the laboratory will provide experience with cutting-edge techniques used in molecular and cellular biology, molecular genetics, mouse genetics and proteomic approaches.  Specifically, molecular cloning, cell culture, gene transfection, one or two-hybrid library screening and transgenic mouse studies etc. will be performed in the lab.

Personnel      

 
Current Research Support (as PI)

Arthritis Foundation:      Arthritis Investigator Award, 2006.7 – 2010.6,

Selected Recent Publications

• D. Napierala, Sam K, Morello R, Zheng Q, Munivez E, Shivdasani RA and B Lee.  Uncoupling of Chondrocyte Differentiation and Perichondrial Mineralization Underlies the Skeletal Dysplasia in Tricho-Rhino-Phalangeal.  Hum Mol Genet. 2008 Apr 17. [Epub ahead of print].
• G. Zhou, Zheng Q, F. Engin, E. Munimez, Y. Chen, E. Sebald, D. Krakow and B. Lee.  Dominance of SOX9 function over RUNX2 during skeletogenesis.  Proc Natl Acad Sci USA 2006 Dec 12;103(50):19004-9.
• Zheng Q, E. Sebald, G. Zhou, Y. Chen, W. Wilcox, B. Lee and D. Krakow.  Dysregulation of Chondrogenesis in Human Cleidocranial Dysplasia.  Am J Hum Genet 2005 Aug; 77(2):305-12.
• D. Napierala, X. Garcia-Rojas, K. Sam, K. Wakui, C. Chen, R. Mendoza-Londono, G. Zhou, Zheng Q and B. Lee.  Mutations and Promoter SNPs in RUNX2, a Transcriptional Regulator of Bone Formation.  Mol Genet Metab 2005 Sep-Oct;86(1-2):257-68.
• Zheng Q, G. Zhou, R. Morello, Y. Chen, X. Garcia-Rojas and B. Lee.  Type X Collagen Gene Regulation by RUNX2 Contributes Directly to Its Hypertrophic Chondrocyte-specific Expression In Vivo.  J. Cell Biol 2003 Sep, 162 (5): 833-842.