Theresa A. Freeman, PhD

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.

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)

• SKMC Profile