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Faculty Affairs: Faculty Interests Database Theresa A. Freeman, PHD

Orthopaedic Surgery
Thomas Jefferson University
Jefferson Medical College
Department of Orthopaedic Surgery
Associate Professor
Faculty Member TERM Program
Mailing Address Contact Information
501 Curtis Bldg., 1015 Walnut St.
Philadelphia, Pennsylvania 19107
United States
Phone: 215-955-1068
Fax: 215-955-9159
1980 - 83 BS University of the Sciences, Philadelphia, PA (Biology)
1992 - 95 MS Rutgers University, Camden, NJ (Biology)
1995 - 96 PhD Rutgers University, New Brunswick, NJ (Biomedical Sciences)
Expertise and Research Interests
The areas of research focus within my laboratory can be divided into 3 main areas:
Osteoarthritis (OA) is a common musculoskeletal disease of aging with multiple etiologies. Factors known to increase susceptibility for this disease include: previous injury, genetics, female gender and increased age and weight. Using microCT technology, our lab investigated differences in trabecular bone remodeling and found the patient samples could be divided into two distinct populations based on subchondral bone characteristics. We hypothesize these differences represent distinct OA subpopulations exhibiting different molecular pathologies.
To investigate this hypothesis, we created a tissue microarray from knee joint tissue samples retrieved from total knee arthroplasty (TKA) surgery of post-menopausal women. We divided these samples into two groups based on subchondral bone characteristics. The results showed the presence and quantity of each protein in each tissue type, creating a quantitative protein localization profile for the tissues of the osteoarthritic joint. Our results show significantly different protein localization and quantity between each tissue type and between the two groups. Additionally, this analysis identifies a specific protein profile which may have implications for differentially identifying proteins involved in early and late OA and differences between the two subchondral trabecular bone remodeling subgroups. Our hope is that this data will lead to the identification of biomarkers and potential drug targets for OA.
Reactive Oxygen Species (ROS) in Chondrocyte Differentiation and Cartilage Degeneration:
In cartilage, ROS signaling plays significant role in regulating chondrocyte proliferation, differentiation and maturation. To assure proper cellular function ROS is balanced by production of antioxidants; as unregulated ROS can cause dysfunction in gene expression, transcription factor signaling, and cell cycle. In aging, systemic disease, environmental toxin exposure, injury and inflammation, ROS production can overwhelm the antioxidant capacity triggering aberrant signaling leading to cell death, matrix degradation and pathological damage in both forming and permanent cartilages. Apoptosis signal-regulating kinase 1 (ASK1) a MAP kinase kinase kinase, is a well characterized protein implicated in pathological ROS signaling and ASk1 is present in growth plate and articular chondrocytes. In cartilage the oxidative status of the cell is controlled by activation of Ask1 by ROS versus the expression of antioxidants. By manipulating the activation of ASK1 we can explore the normal and pathological role of ROS in chondrocyte differentiation. Our hope is that these studies will have an enormous impact on understanding molecular mechanisms of oxidative stress in chondrocytes thereby providing important information for developing novel targets for therapeutic intervention.
Non-Thermal Plasma activation of Cellular Differentiation for Tissue Regeneration:
Non-thermal dielectric barrier discharge plasma is a relatively new physics-based technology. Currently, the application of this technology to biological sciences is almost non-existent. The main focus of the few published reports there are, is that NT-plasma effects cell function through the activation of ROS and RNS signaling pathways. In collaboration with the A. J. Drexel Plasma Institute, our goal is to create an NT-Plasma system to specifically manipulate cellular redox and thereby enhance the commitment and differentiation of MSCs along osteogenic and chrondrogenic lineages. A strong literature base supports the role of oxidative signaling as a mechanism to initiate transitions during stem cell differentiation in vivo. If we are successful, the potential benefit of this investigation is twofold; the development of NT-Plasma as a new biotechnology and the control of MSC function in differentiation and commitment. As such, our hope is that NT-Plasma can be developed to provide a new mechanism by which alterations in cellular metabolism can initiate a signal transduction cascade in pluripotent cells to promote their proliferation, commitment and differentiation.
Other Expertise
Industry Associated Positions:

1997 - 2004 Applications Scientist, Phase 3 Imaging Systems, Inc., Glen Mills, PA

Postgraduate Training and Fellowship Appointments:
1996 Post-Doctoral Fellow, New Jersey Department of Human Services
1997 - 1998 Director, Cell Morphology Core, Institute of Human Gene Therapy
1998 - 2004 Applications Scientist, Phase 3 Imaging Systems, Inc., Glen Mills, PA
2004 - 2005 Research Associate, Department of Orthopaedic Surgery at Thomas Jefferson University

Faculty Appointments:
1997 - 1998 Research Assistant Professor, Department of Molecular Genetics, Univ. of Penn
2006 - Present Tenure-track Assistant Professor, Department of Orthopaedic Surgery

Memberships in Professional and Scientific Societies:
1994 - Present American Association for the Advancement of Science
2005 - 2009 American Society for Bone and Mineral Research
2006 - Present Orthopaedic Research Society

Academic Committees at Thomas Jefferson University:
Thomas Jefferson University Research Strategic Planning Committee Member 2010 - 2011
Thomas Jefferson University Graduate School Faculty - Tissue Engineering and Regenerative Medicine and Cell and Developmental Biology

Major Teaching Responsibilities at Thomas Jefferson University and other Universities:
2006 - Present - Lecturer Tissue Engineering and Regenerative Medicine Courses
2006 - Present - Host Laboratory for School of Health Sciences Student Rotations
1996-97 - Functional Histology, Jefferson College of Health Professions
1995-96 - Histology Laboratory, UMDNJ
1994-96 - Comparative Anatomy, Lecture and Lab, Rutgers University
1986-1992 - Anatomy and Physiology, Chemistry, Biology Lab, Burl. County Comm. College

  • 1. Ravindra, R., Nagele, R., Patel, S., Freeman, T., (1994) Membrane-associated tubulin in the rat anterior pituitary and GH3 cells. Neuroreport, 5, pgs. 1653-1656
  • 2. Nagele, R., Freeman, T.**, McMorrow, L., Lee, H., (1995) Precise spatial positioning of chromosomes during prometaphase: Evidence for chromosomal order in human cells. Science, Vol. 270, pgs. 1831-1835
  • 3. Bals, R., Wang, X., Wu, Z., Freeman, T., Bafna, V., Zasloff, M., Wilson, J.M. (1998) Human Beta- Defensin 2 is a salt sensitive peptide antibiotic expressed in human lung. J. Clin. Invest., Vol. 102( 5)
  • 4. Nagele, R, Freeman, T., Fazekas, J., Lee, K., Tejera, Z., Lee, H., (1998) Chromosome Spatial Order in Human Cells: Evidence for Early Origin and Faithful Propagation. Chromosoma*, Vol. 102(5), pgs. 874-880
  • 5. Nagele, R, Freeman, T., McMorrow, L., Tejera, Z., Kitson-Wind, K., Lee, H., (1999) Chromosomes exhibit preferential positions in nuclei of quiescent Human cells that reflects their arrangement in mitotic chromosome rosettes. J. Cell Sci., Vol. 1124, pgs. 525-535
  • 6. Pacifici, M., Shimo, T., Gentili, C., Kirsch, T., Freeman, T.A., Enomoto-Iwamoto, M., Iwamoto, M., Koyama, E. (2005) Syndecan-3: a cell-surface heparan sulfate proteoglycan important for chondrocyte proliferation and function during limb skeletonogenesis. J. Bone Miner Metab 23:191-199 2005
  • 7. Shapiro, I.M., Adams, C.S., Freeman, T., and Srinivas, V., The fate of the hypertrophic chondrocyte: Microenvironmental perspectives on apoptosis and survival in the epiphyseal growth plate. (2005) Birth Defects Research Part C: Embryo Today: Reviews. 75(4): 330-339
  • 8. Szymczyk, K, Kerr BAE, Freeman, TA, Adams, CS, Steinbeck, MJ (2006) Involvement of Hydrogen Peroxide in the Differentiation and Apoptosis of Preosteoclastic Cells Exposed to Arsenite, Biochem Pharmacol. Sep 14; 72(6):761-9.
  • 9. Szymczyk, K, Freeman, TA, Adams, C, Srinivas, V, Steinbeck, MJ (2006) Active Caspase-3 is required for Osteoclast Differentiation, J. of Cell. Phys. Dec; 209(3):836-44
  • 10. Jacob S, C Wu, TA Freeman, E Koyama, RE Kirschner, Expression of Indian hedgehog, BMP-4 and Noggin in craniosynostosis induced by fetal constraint. (2007) Ann Plast Surg. Feb; 58(2):215-221
  • 11. Pucci, B., Adams, C. S., Fertala, J, Snyder, B. C., Mansfield, K. D., Tafani, M, Freeman, T Shapiro, I. M. Development of the terminally differentiated state sensitizes epiphyseal chondrocytes to apoptosis through caspase-3 activation. (2007) J Cell Physiol. Mar; 210(3):609-15.
  • 12. Han, F., Gilbert, J. R., Adams, C.S., Harrison, G., Freeman, T., Tao, Z., Zaka, R., Liang H., Williams, C., Tuan, R. S., Norton, P. A., Hickok, N.J. Transforming Growth Factor s1 regulates fibronectin isoform expression and splicing factor SRp40 expression during ATDC5 chondrogenic maturation. (2007) Exper. Cell Res. May 1; 313(8):1518-32
  • 13. Antoci V. Jr, King S.B., Jose B., Parvizi J., Zeiger A.R., Wickstrom E., Freeman T.A., Composto R.J., Ducheyne P., Shapiro I.M., Hickok N.J., Adams C.S. (2007) Vancomycin covalently bonded to titanium alloy prevents bacterial colonization. J. Orthop. Res. Jul;25(7):858-66.
  • 14. Kerr, B.A., Otani, T., Koyama, E., Freeman, T.A., Enomoto-Iwamoto, M., (2008) Small GTPase protein Rac-1 is activated with maturation and regulates cell morphology and function in chondrocytes. Exp Cell Res. Apr 1; 314 (6):1301-12. Epub 2008 Jan 18
  • 15. Watanabe H, Bohensky J, Freeman T, Srinivas V, Shapiro IM. (2008) Hypoxic induction of UCP3 in the growth plate: UCP3 suppresses chondrocyte autophagy. J Cell Physiol. Aug; 216(2):419-25.
  • 16. Antoci, V, Adams, CS, Parvizi, J, Davidson, HM, Composto, RJ, Freeman, TA, Wickstrom, E, Zeiger, AR, Ducheyne, P, Jungkind, D, Shapiro, IM, Hickok, NJ (2008) Vancomycin-modified Ti alloy inhibits S. epidermidis biofilm formation: Implications for treatment of periprosthetic infection. Biomaterials, Dec; 29 (35): 4684-90. Epub. Sept. 23 19.
  • 17. Freeman, TA, Patel, P, Antoci V. Jr, Shapiro IM (2009) MicroCT Analysis with Multiple Thresholds Allows Detection of Bone Remodeling Events During Ultrasound-Treated Fracture Healing. J Orthop Res. May; 27(5):673-9.
  • 18. Adams, CS, Antoci, V Jr, Harrison, G, Patal, P, Freeman, TA, Shapiro, IM, Parvizi, J, Hickock, NJ, Radin, S, Ducheyne, P (2009) Controlled Release of Vancomycin from Thin Sol-Gel Films on Implant Surfaces Successfully Inhibits Osteomyelitis. J Orthop Res. 2009 Jun;27(6):701-9
  • 19. Bohensky J, Terkhorn SP, Freeman T, Adams CS, Garcia J, Shapiro IM and Srinivas V (2009) Regulation of Autophagy in Cartilage: HIF-2 Suppresses Chondrocyte Autophagy. Arthr. And Rheum May; 60(5):1406-15
  • 20. Zaka R, Dion AS, Kusnierz A, Bohensky J, Srinivas V, Freeman TA, Williams CJ. (2009) Oxygen tension regulates the expression of ANK (progressive ankylosis) in a HIF-1 dependent manner in growth plate and articular chondrocytes. J Bone Miner Res. 2009 Nov;24 (11):1869-78
  • 21. Steinbeck, M.J., Baxter, R.M., and Freeman, T.A. (2009) Pathophysiologic Reactions to UHMWPE Wear Particles. In: The UHMWPE Biomaterials Handbook, 2nd Edition SM Kurtz,
  • 22. Freeman TA, Parvizi J, Della Valle CJ, Steinbeck MJ. (2009) Reactive oxygen and nitrogen species induce protein and DNA modifications driving arthrofibrosis following total knee arthroplasty. Fibrogenesis Tissue Repair. Nov 13; 2 (1):5.
  • 23. Oca, P, Zaka, R, Dion, A, Freeman, T, Williams, C. (2010) Phosphate and calcium are required for TGF²-mediated stimulation of ANK expression and function during chondrogenesis J Cell Physiol. Aug; 224(2):540-8.
  • 24. Skubutyte R , Markova D , Freeman TA , Anderson DG, Dion AS, Williams CJ, Shapiro IM, Risbud MV. (2010) HIF Regulation of ANK Expression in Nucleus Pulposus Cells: Possible Implications in Controlling Dystrophic Mineralization in the Intervertebral Disc. Arthrit. and Rheum. (Sep; 62 (9):2707-15)
  • 25. Freeman TA, Parvizi J, Della Valle CJ, Steinbeck MJ. (2010) Mast Cells and Hypoxia Drive Tissue Metaplasia and Heterotopic Ossification in Idiopathic Arthrofibrosis After Total Knee Arthroplasty. Fibrogenesis Tissue Repair (Sep 1; 3: 17)
  • 26. Baxter, RM, Ianuzzi, A, Freeman, TA, Kurtz, SM, Steinbeck, MJ (2010) Distinct Immunohistomorphologic Changes in Periprosthetic Hip Tissues from Historical and Highly-crosslinked UHMWPE Implant Retrievals. J Biomed Mater Res B Appl Biomater (Oct; 95 (1):68-78)
  • 27. Baxter RM, Freeman TA, Kurtz SM, Steinbeck MJ. (2011) Do tissues from THA revision of highly crosslinked UHMWPE liners contain wear debris and associated inflammation? Clin Orthop Relat Res. 2011 Aug;469(8):2308-17
  • 28. Casper DS, Kim GK, Parvizi J, Freeman TA (2012) Morphology of the Proximal Femur Differs Widely with Age and Sex: Relevance to Design and Selection of Femoral Prostheses, J. Orthop. Res.Jul;30(7):1162-6.
  • 29. Liu Q, Limthongkul W, Sidhu G, Zhang J, Vaccaro A, Shenck R, Hickok N, Shapiro I and Freeman T (2012) Covalent attachment of P15 peptide to titanium surfaces enhances cell attachment, spreading, and osteogenic gene expression, J Orthop Res. Oct;30(10):1626-33. doi: 10.1002/jor.22116. Epub 2012 Apr 1330.
  • 30. Acharya NK, Levin EC, Clifford PM, Han M, Tourtellotte R, Chamberlain D, Pollaro M, Coretti NJ, Kosciuk MC, Nagele EP, Demarshall C, Freeman T, Shi Y, Guan C, Macphee CH, Wilensky RL, Nagele RG. J (2013) Diabetes and hypercholesterolemia increase blood-brain barrier permeability and brain amyloid deposition: beneficial effects of the LpPLA2 inhibitor darapladib., Alzheimers Dis. Jan 1;35(1):179-98.
  • 31. Zhou J, Freeman TA, Ahmad F, Shang X, Mangano E, Gao E, Farber J, Wang Y, Ma XL, Woodgett J, Vagnozzi RJ, Lal H, Force T., (2013) GSK-3± is a central regulator of age-related pathologies in mice., J Clin Invest. 2013 Apr 1;123(4):1821-32
  • 32. Steinbeck MJ, Chernets N, Zhang J, Kurpad DS, Fridman A, Fridman G, Freeman, TA, (2013) Skeletal Cell Differentiation is Enhanced by Atmospheric Dielectric Barrier Discharge Plasma Treatment., PLoS One. 2013, Dec 12;8(12):e82143.
  • 33. Steinbeck, MJ, Jablonowski, LJ, Parvizi, J, Freeman, TA (2013) The Role of Oxidative Stress in Aseptic Loosening of Total Hip Replacements, J Arthroplasty. 2014 Apr; 29(4):843-9, Epub 2013 Nov 26.
  • 34. Majeed SR, Vasudevan L, Chen C-Y, Luo Y, Torres JA, Evans TM, Sharkey A, Foraker AB, Esk C, Freeman TA, Moffett A, Keen JH and Brodsky FM, (2014) Clathrin light chain binding to Huntington interacting proteins is required for recycling during cell migration. (accepted, Nature Communications)
  • 35. Chernets N, Zhang J, Steinbeck MJ, Kurpad DS, Koyama E, Friedman G, Freeman TA, (2014)
  • Non-Thermal Atmospheric Pressure Plasma Enhances Mouse Limb Bud Survival, Growth and Elongation (in revision, Tissue Engineering Part A)
  • 36. Lou Y, Siglin A, Dawn A, Freeman TA, Keen JH (2014) Development and application of an inducible dynein intermediate chain antagonist. (manuscript submitted, TRAFFIC)
  • 37. Steinbeck MJ, Patel P, Opest A, Davis D, Parvizi J, Freeman TA (2014) Identification of Distinct Osteoarthritic Pathology based on Patient-Specific Subchondral Trabecular Bone Subtype (manuscript in preparation)
  • 38. Zhang J, Sidhu GS, Liu QY, Vaccaro AR, Diallo C, Kaya O, Shapiro IM, Fertala A, Freeman TA (2014) P15 Peptide Enhances Chondrogenesis and Endochondral Ossification (manuscript in preperation)
  • 39. Opest, A, Steinbeck MJ, Patel, P, Parvizi, J, Freeman, TA (2014) Tissue Microarray analysis of Osteoarthritic Joint Reveals Tissue and Disease Specific Molecular Etiologies (manuscript in preparation)
  • 40. Eaton, G, Diallo, C, Roszyka, M, Freeman, TA (2014) Apoptosis signal-regulating kinase (ASK1) Sub-Cellular Localization during Chondrocyte Differentiation effect p38 and JNK signaling. (manuscript in preparation)
  • * Chromosoma paper of the year, 1998; ** joint first author
  • Editorials, Reviews, Chapters
  • Pacifici, M., Shimo, T., Gentili, C., Kirsch, T., Freeman, T.A., Enomoto-Iwamoto, M., Iwamoto, M., Koyama, E. (2005) Syndecan-3: a cell-surface heparan sulfate proteoglycan important for chondrocyte proliferation and function during limb skeletonogenesis. J. Bone Miner Metab 23:191-199
  • Shapiro, I.M., Adams, C.S., Freeman, T., and Srinivas, V., The fate of the hypertrophic chondrocyte: Microenvironmental perspectives on apoptosis and survival in the epiphyseal growth plate. (2005) Birth Defects Research Part C: Embryo Today: Reviews. 75(4): 330-339
  • Shapiro, I.M., Adams, C.S., Srinivas, V., and Freeman, T.A. (2006) Chondrocyte Hypertrophy and Apoptosis at the Cartilage-Bone Interface. In: Bone and Osteoarthritis (Topics in Bone Biology Vol 4)(F. Bronner and M.C. Farach-Carson, eds.).
  • Steinbeck, M.J., Baxter, R.M., and Freeman, T.A. (2009) Pathophysiologic Reactions to UHMWPE Wear Particles. In: The UHMWPE Biomaterials Handbook, 2nd Edition SM Kurtz,

Last Updated by Theresa Freeman, PHD: Wednesday, September 5, 2012 1:52:33 PM

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