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Hicham Drissi, PhD

Academic Title
Associate Professor of Orthopaedics and Research Director

Primary Appointment
Department of Orthopaedics

Secondary Appointment
Department of Genetics

Relevant Activities and Interests
Areas of interest: The areas of research in my laboratory relate to defining the cellular and molecular pathways that govern skeletal tissue development and repair. We aim to better understand the mechanisms by which stem cells mediate the regulation of endochondral ossification. Specifically, we investigate growth control and differentiation of these progenitor cell populations into chondrocytes and osteoblasts. A significant part of our efforts have been committed to investigating transcriptional control in vitro and in vivo. These areas of interest provide direct translational applications to orthopaedic problems ranging from osteoarthritis to skeletal dysplasia.

Current programs: One of our programs aims to determine the molecular mechanisms of fracture repair using animal models. This was initiated via investigating the role of the Runx family of transcription factors in mediating cartilage development and repair. We have established the function of Runx1 as an early mediator of mesenchymal cell commitment towards chondrogenesis while Runx2 controls hypertrophy and cartilage mineralization. Runx3 appears to affect both early and late stages of chondrogenesis and chondrocyte maturation. We are now using various mouse models to address the effects of bone anabolic treatments such as Teriparatide on these and other downstream factors in order to understand how they contribute fracture healing.

The purpose of our second program is to identify the molecular signals responsible for or resulting from chondrodysplasia and osteoarthritis. In this program we aim to identify the molecular switches that control the transition from immature to mature chondrocytes in response to factors that play differential roles in this process. More specifically, we are focused on stage-specific cooperative versus antagonistic effects of various growth factors such as Wnt, TGF-beta and BMP2 during cartilage formation. We have identified Runx2 and Twist1 as key players in these events. We are using genetic models and surgery induced osteoarthritis to verify the relevance on these pathways to the progression of cartilage degenerative diseases. This is complemented with a translational component in which articular cartilage explant models from human discarded joints are used. We are currently actively investigating the viability of various cell-based therapeutic approaches using these models.

Selected Publications

  • Li T-F, Dong Y, Ionescu AM, Rosier RN, Zuscik MJ, Schwarz EM, O’Keefe, RJ, Drissi H. 2004. Parathyrod hormone-related peptide (PTHrP) inhibits Runx2 expression through the PKA signaling pathway. Experimental Cell Research. Sep 10 299(1);128-36.
  • Smith N, Dong Y, Lian JB, Pratap J, Kinsley PD, van Wijnen AJ, Stein JL, Schwarz EM, O’Keefe RJ, Stein GS, Drissi H. 2005.Overlapping Expression of Runx 1 (Cbfa1) Transcription Factors Supports Cooperative Induction of Skeletal Development. J Cell Physiol. Apr;203(1):133-43.
  • Zou W, Amcheslavsky A, Takeshita S, Drissi H, Bar-Shavit Z. 2005. TNF-α Expression is Transcriptionally Regulated by RANK Ligand. J Cell Physiol. Feb; 202(2):371-8.
  • Wei X., Zhang X., Zuscik MJ., Drissi H., Schwarz EM., O'Keefe RJ. 2005.  Fibroblasts express RANKL and Support Osteoclastogenesis in Cox-2 Dependent Manner Following Stimulation with Titanium Particles. Journal of Bone and Mineral Research July; 20(7): 1136-48.
  • Wang Y, Belflower RM, Dong Y, Schwarz EM, O'Keefe RJ, Drissi MH. 2005 Runx1/AML1/cbfa2 mediates Onset of Mesechymal Cell differentiation Towards Chondrogenesis. Journal of Bone and Mineral Research, Sep; 20(9): 1624-36.
  • Roman Eliseev, Michael Zuscik, Edward Schwarz, Regis O'Keefe, Hicham Drissi and Randy Rosier. 2005. Increased Radiation-induced apoptosis of Saos2 cells via inhibition of NFkappaB: A role for c-Jun N-terminal Kinase., Journal of Cellular Biochemistry. Dec 15; 96(6): 1262-73.
  • Eliseev, R.A., Schwarz, E.M., Zuscik, M.J., O’Keefe, R. J., Drissi, H., and R.N. Rosier. 2006. Smad7 Mediates Inhibition of Saos2 Osteosarcoma Cell Differentiation by NFkB. Experimental Cell Research Jan 1; 312(1): 40-50.
  • Li TF., Darowish M., Zuscik MJ., Chen D., Schwarz EM., Rosier RN., Drissi H., and O’Keffe RJ. 2006 SMAD3 deficient chondrocytes have enhanced BMP signaling and accelerated differentiation. Journal of Bone and Mineral Research. Jan; 21(1): 4-16.
  • Yasuhiko Nishio; Yu-Feng Dong; Mark Paris; Regis J. O’Keefe; Edward M. Schwarz; and Hicham Drissi. 2006 Runx2 regulation of the zinc finger protein Osterix. Gene. May 10;372:62-70
  • Yu-Feng Dong; DoYu Soung; Edward M. Schwarz; Regis J. O’Keefe; and Hicham Drissi. 2006. Wnt induction of chondrocyte hypertrophy through the Runx2 transcription factor. Journal of Cellular Physiology. Jul;208(1):77-86
  • Michael D. Maloney, j. Jeffrey Goater, Richard Parsons, Himoru Ito, Regis J. O’Keefe, Paul T. Rubery, Hicham Drissi and Edward M. Schwarz. 2006. Safety and efficacy of long-wavelength ultraviolet light activated gene transduction for site specific gene therapy of articular cartilage defects. J Bone Joint Surg Am. Apr; 88 (4): 753-61.
  • Soung DY, Dong Y, Wang Y, Zuscik MJ, Schwarz EM, O'keefe RJ, Drissi H. 2007 Runx3/AML2/Cbfa3 Regulates Early and Late Chondrocyte Differentiation. J Bone Miner Res. May 8.
  • Lee A. Kaback, Do Y. Soung, Amish Naik, Nathan Smith, Edward M. Schwarz, Regis J. O’Keefe; and Hicham Drissi. 2008 Osterix/Sp7 Regulates Mesenchymal Stem Cell Mediated Endochondral Ossification. J Cell Physiol. Jan;214(1):173-82
  • Li. D. Gromov K.; Soballe K.; Puzas JE.; O’Keefe RJ.; Awad H.; Drissi H.; and Schwarz EM. 2008. Quantitative mouse model of implant-Associated osteomyelitis and the kinetics of microbial growth, ostelysis and humoral immunity J Orthop Res; Jan;26(1). 96-105
  • Lee A. Kaback, Do Y. Soung, Amish Naik, Grazielo Geneau, Edward M. Schwarz, Randy N Rosier, Regis J. O’Keefe; and Hicham Drissi. 2008 Teriparatide (1-34 human PTH) regulation of Osterix during fracture healing. J Cell Biochem Sep 1; 105 (1):219-26.
  • Roman A. Eliseev, Yu-Feng Dong, Erik Sampson, Michael J. Zuscik, Edward M. Schwarz, Regis J. O’Keefe, Randy N. Rosier and M. Hicham Drissi. 2008. Runx2-mediated activation of the Bax gene increases osteosarcoma cell sensitivity to apoptosis. Oncogene. 27, 3605-3614.
  • Wu Q, Kim KO, Sampson ER, Chen D, Awad H, O'Brien T, Puzas JE, Drissi H, Schwarz EM, O'Keefe RJ, Zuscik MJ, Rosier RN. 2008; Induction of an osteoarthritis-like phenotype and degradation of phosphorylated Smad3 by Smurf2 in transgenic mice. Arthritis Rheuma. Sep 29;58(10):3132-3144.
  • Fritz V, Noël D, Bouquet C, Opolon P, Voide R, Apparailly F, Louis-Plence P, Bouffi C, Drissi H, Xie C, Perricaudet M, Muller R, Schwarz E, Jorgensen C. 2008; Antitumoral Activity and Osteogenic Potential of hATF-Expressing Mesenchymal Stem Cells In A Murine Model of Osteolytic Tumor. Stem Cells. Aug 28.
  • Amish Naik; Chao Xie; Paul Kingsley; Michael J Zuscik; Edward M Schwarz; Hani Awad; Robert Guldberg; Hicham Drissi; Edward Puzas; Brendan Boyce; Xinping Zhang; Regis J. O'Keefe. 2009; Reduced COX-2 expression in aged mice is associated with impaired fracture healing. J Bone Miner Res. 2009 Feb;24(2):251-64.
  • Rahima Akter; Daniel Rivas; Graziello Geneau; Hicham Drissi; Gustavo Duque. 2009; Effect of Lamin A/C Knockdown on Osteoblast Differentiation and Function. J Bone Miner Res. Feb;24(2):283-93.
  • Liping Xiao, Peng Liu, Xiaofeng Li, Thomas Doetschman, J. Douglas Coffin, Hicham Drissi, Marja M. Hurley. 2009; The exported 18KD isoform of FGF2 is a critical determinant of bone mass In mice. J Biol Chem. Jan 30;284(5):3170-82.
  • Wei X, Zhang X, Flick LM, Drissi H, Schwarz EM, O’Keefe RJ. 2009 Titanium particles stimulate COX-2 expression in synovial fibroblasts through an oxidative stress-induced, calpain-dependent, NF-kappaB pathway. Am J Physiol Cell Physiol Aug;297(2):C310-20.
  • Huang H, Chikazu D, Voznesensky OS, Hershman HR, Kream BE, Drissi H, Pilbeam CC. 2009 Parathyroid Hormone Induction of Cyclooxygenase-2 in Murine Osteoblasts: Role of the Calcium-Calcineurin-NFAT Pathway.J Bone Miner Res Oct 12.

Contact Information
Medical Arts & Research Building, Suite 4048
263 Farmington Ave
Farmington, CT, 06034

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