Theresa A Freeman, MS, PhD

Associate Professor, Orthopaedic Surgery, Cell and Developmental Biology

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Dr. Freeman received Masters and PhD degrees from Rutgers University in 1995 and 96, respectively, and in 1996, was appointed Research Assistant Professor and Assistant Director of the Cell Morphology Core for the Institute of Human Gene Therapy at the University of Pennsylvania.  In 1997, she left academia to work as an Application Scientist consulting with pharmaceutical and academic laboratories to automate their microscopy and image analysis applications. She returned to academia in 2004, as Research Associate in the Department of Orthopaedic Surgery, Thomas Jefferson University, and was promoted to tenure-track Assistant Professor in 2006 and Associate Professor in 2012.  Dr. Freeman obtained several grants from NIH focused on the role of reactive oxygen species in skeletal cell differentiation, repair, regeneration and degeneration. She collaborated with academic and industrial engineers to integrate new technologies into orthopaedic applications. She is currently collaborating with the University of Delaware to develop histone-targeted, non-viral gene therapies for bone defect repair. Additionally, she is involved in pioneering work in the field of plasma medicine collaborating with plasma physicists at Drexel University.  Dr. Freeman is on the Board of Directors for the International Society of Plasma Medicine and is an editor of the Journal of Plasma Medicine. Additionally, she is President of the Thomas Jefferson University Chapter of Sigma Xi.

Areas of research focus in her laboratory are detailed below:

PLASMA MEDICINE - Plasma medicine utilizes physics-based technology of non-thermal atmospheric plasmas for treatment of biological tissues. Dr. Freeman is currently testing microsecond-and-nanosecond pulsed dielectric barrier discharge plasmas (DBD), non-thermal plasma (NT-plasma), to manipulate cellular redox to enhance skeletal cell differentiation, limb development and regeneration. NT-plasma influences cell function mainly through activation of reactive oxygen and nitrogen species (ROS/RNS) signaling pathways. Her NIH-funded study is based on her earlier studies that NT-Plasma promotes reactive oxygen species generation and enhances development of embryonic structures initiating expression of many genes linked to cell differentiation. She hopes to delineate mechanisms by which NT-Plasma generated ROS/RNS promotes MSC proliferation, commitment and differentiation; while simultaneously developing a device for this application. Her work provides an opportunity to evaluate potential and feasibility of NT-plasma treatment to enhance tissue repair and regeneration, while gaining an understanding of the resulting signaling networks.

APOPTOSIS SIGNAL-REGULATED KINASE1 (ASK1) – ASK1 is involved in transduction of several ROS-dependent pathologies including; cardiomyocyte hypertrophy, neuronal degeneration, LPS-induced arthritis and bacterial sepsis.  Her laboratory has preliminary data showing that ASK1 knockout mice also have increased regenerative capacity in several models. These mice can regenerate ear tissue after punch, have resistance to meniscectomy-induced arthritis and show increased bone formation during development and in an ectopic bone formation model, as compared to wild-type mice. Dr. Freeman hypothesizes inhibition of ASK1 activation enhances the regenerative environment by decreasing cell death and reducing pro-inflammatory cytokine production and their catabolic effects.  Thus, in this way ASK1 inhibition promotes the activation of repair cascades by endogenous cells to generate a more robust healing/regenerative response. If correct, therapeutic application of an ASK1 inhibitor holds promise in protecting cartilage or bone after injury and to generally enhance repair and regeneration.

HISTONE-TARGETED, NON-VIRAL GENE DELIVERY TO ENHANCE BONE REPAIR (In collaboration with Dr. Sullivan at the University of Delaware) - The goal of this research is to create and optimize multifunctional “designer” histones decorated on nanogold (NG) scaffolds to induce efficient gene transfer, and ultimately, enable improved bone repair. They hypothesize that polycationic NG coupled to histone motifs will mimic native presentation on histone octamers and create structures which will stably bind and deliver plasmid DNA (pDNA). They are investigating how to determine NG-pDNA dosing and BMP-2 expression levels to safely and effectively deliver in vivo BMP-2 sufficient to induce ossification and promote repair in murine heterotopic ossification and rat bone defect models.  This work was recently funded by a $1.4-million dollar grant from the National Institute of Biomedical Imaging and Bioengineering at NIH.