Theresa A. Freeman, PhD
Associate Professor, Department of Orthopaedic Surgery
Contact
1015 Walnut Street
501 Curtis Building
Philadelphia, PA 19107
215-955-1068
215-955-9159 fax
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Theresa A. Freeman, PhD
Associate Professor, Department of Orthopaedic Surgery
Expertise & Research Interests
The areas of research focus within my laboratory can be divided into 3 main areas:
Osteoarthritis
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.
Education
PhD, Biomedical Sciences, Rutgers University/University of Medicine and Dentistry of NJ, New Brunswick, NJ (1996)
MS, Biology, Rutgers University, Camden, NJ (1995)
BS, Biology, University of the Sciences, Philadelphia, PA (1983)
Publications
- Geranylgeraniol (GGOH), incorporated into a bone cement pellet promotes osteoclast function and healing in a model of medication-related osteonecrosis of the jaw
- Evaluating the Healing Potential of J-Plasma Scalpel-Created Surgical Incisions in Porcine and Rat Models
- Cold atmospheric pressure plasma-antibiotic synergy in Pseudomonas aeruginosa biofilms is mediated via oxidative stress response
- Microbubble cavitation restores Staphylococcus aureus antibiotic susceptibility in vitro and in a septic arthritis model
- Cartilage-specific Sirt6 deficiency represses IGF-1 and enhances osteoarthritis severity in mice
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 - 2012 Assistant Professor, Department of Orthopaedic Surgery
2012 - Present Tenure-track Associate 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