Education and Experience:
Ph.D. degree earned May, 2001Program in Developmental Biology and Teratology.
Department of Pathology, Cell Biology and Anatomy
Thomas Jefferson University, Philadelphia, PA
“The Role of Paraxis in Somitogenesis and Carbon Monoxide-Induced Axial Skeletal Dysmorphogenesis”
B.S./B.A. degrees in Biology and Studio Art earned in May 1990
College of Arts and Sciences, Wake Forest University, Winston-Salem, NC
Dean’s List 1988, 1989, 1990
1st Place Wake Forest University Senior Art Show
My background includes research in developmental biology, mechanisms of teratology and reproductive toxicology, orthopaedic surgery, stem cell biology, and tissue engineering.
· Investigating the fate of adult stem cells in embryonic chimeric cultures
· The role of stem cells and specific cell signaling systems in osteoarthritis (OA).
· Development of in vitro and in vivo models to study the early pathogenesis of OA
· Cell-based tissue engineering approaches to articular cartilage repair, nerve and tendon
· Development of bioreactors and microphysiological cultures for the study of tissue development, homeostasis and pathogenesis
· Organotypic models for in vitro testing of developmental toxicants and probing mechanisms of metastasis and potential therapeutic interventions.
I thoroughly enjoy the interdisciplinary nature of the work and environment this type of research demands. It provides inspiration and fertile ground for new and productive research avenues that I find very fulfilling. Active areas of research that we are pursuing include:
· Customized fabrication of condylar osteochondral tissue for joint surface repair
· Development of a novel cell-based therapeutic agent for prevention and treatment of osteomyelitis
· Trauma-induced heterotopic ossification: cellular and molecular targets for clinical intervention
· Regenerative repair of traumatic articular cartilage injuries: point-of-care use of mesenchymal stem cells, PRP and chondrocytes
· Application of adult stem cells and native tissue matrices for tissue regeneration
· Ground-based analysis of the effects of microgravity on intervertebral disc development: An in vitro tissue tngineering-based model utilizing adult stem cells
· Mechanism of skeletal dysmorphogenesis in the WDPCP mutant mouse
· Application of adult mesenchymal stem cells and induced pleuripotent mesenchymal progenitor cells to osteochondral microtissue formation and testing for the study of disease pathogenesis, embryotoxicity, and drug screening.
Common themes that run through these applications are the use of stem cells in tissue engineering either as a participant or mediator of regenerative processes, the development of in vitro and/or in vivo models with which to test specific cell and tissue interactions, developmental or pathogenic processes, and the use bioreactors to recapitulate specific cell and tissue interactions to produce physiological systems that more faithfully report disease processes and therapeutic outcomes.
igure 1: (A) Arthoscopic image of fibrillated articular cartilage in the knee. (B) Safranin /Fast Green staining of articular cartilage obtained as surgical waste from patients undergoing total knee arthroscopy (IRB approved); (C) Notch ligand distribution in osteoarthritic articular cartilage (Steven Koehler); (D) Stem cell adhesion to different substrates including osteoarthritic cartilage (Ofer Levy); (E) Localization of MSCs in osteoarthritic cartilage explants 7 days after seeding; (F) iNOS and HO1 protein localization in surface and deep zones of osteoarthritic articular cartilage (Knee).
igure 2:(A) Somite morphology at diferent stages of development within a Hamburger-Hamilton stage 13 chick embryo (from Schoenwolf); Victoria Blue B-stained day 8 chick embryos cultured in air (left) and 1000 ppm carbon monoxide (right) between 36 and 54 hours of development; (C) paraxis expression detected by in situ hybridization 18 hours after culture in air and 1000ppm CO; (D) CO-induced scoliosis in chick embryo; (E) localization of cell death detected by acridine orange in 54 hour embryos after 18 hours of culture in air (left) and 1000ppm CO (right). Induction of HIF1 a protein production (detected by western and immunohistochemistry) and targets specific to anaerobic metabolism in 54 hour embryos treated with CO for 18 hours. Induction of iNOS and HO1 in CO-treated embryos.
Figure 3: (A) Impactor in an armature used for in vitro impact; (B) Impactor with a reveal of its internal mechanism and proposed site of intra-articular impact for inducing focal osteoarthritic degeneration in a rabbit model; (C) A lesion on a rabbit medial femoral condyle stained with india ink 24 hours after impact. (D) Osteoarthritic lesion 3 months after impact, paraffin embedded, serially sectioned and stained with Safranin O/Fast Green. (E) Force vs Time curve during a 17 and 36 MPa impact as detected by load cells on the projectile (black) and under the subchondral bone (grey); (F) Confocal imaging of live and dead cells with articular cartilage following a 36 MPa impact.
igure 4: (A) Hood set-up for in vivo injection of stem cells; (B) a day 4 chick embryo in window culture; (C) a day 4 chick limb bud after injection of 10,000 DiI-labeled adult human MSCs in 10 nL in bright-field and epi-fluorescent imaging (with overlay); (D) location of DiI-labeled MSCs in after 4 days of development (ina day 8 chick limb); (E) Efficiency of MSC labeling with GFP-expressing plasmid (PC-DNA); (F) Phase contrast impage of a day 8 chick limb that had been injected with 10,000 DiI-labeled MSCs on day 4. Red boxes correspond to close-ups under epi-fluoescent microscopy revealing the location of DiI-labeled stem cell (arrows) within different tissues.
Fig. 5: (A) Randomly-aligned nanofiber mats (Wan-ju Li); (B) stem cells adherent to randomly-aligned nanofibers (Wan-ju Li); (C) appearance of plain (left) and nanofiber-infused agarose, photocrosslinked-gelatin and alginate hydrogel constructs and the effect of nanofiber inclusion on hydrogel mechanical properties (Riccardo Gottardi); (D) surgical procedure for implantation of nanobrous constructs in a rabbit model; (E) location and survival of cells 28 days after implation: Alcian Blue staining (top) and Hoechst 33342 DNA stain (bottom).