Resume

• 1990

  Doctor of Philosophy (Ph.D.)

  Dissertation title: Effects of matrix constituents and growth factors on odontoblast differentiation.

  Developmental Biology

  University of Strasbourg

• 1989

  French

  Master of Science (MS)

  Cellular and Molecular Biology

  University of Strasbourg

• 1986

  Bachelor of Science (B.S.)

  Studied Physiology

  Cellular Biology

  and Molecular Biology at the undergraduate level.

  Biology and Biochemistry

  University of Strasbourg

  Northeast Summer Institute on Scientific Teaching -University of Connecticut

  Storrs

  CT

  Molecular Embryology of the Mouse Course

  Cold Spring Harbor

• 944

  Injectable Delivery System for Heparin-Binding Growth Factors

  us

  14/004

  Jia X

• The CIRTL Network

  Dog walking

  Delaware Humane Association

  Mentor

  The Summer Institutes on Scientific Teaching

  Molecular Genetics

  qPCR

  Bone and Cartilage Diseases

  Western Blotting

  Tooth development

  Molecular Biology

  Cell Culture

  Transgenics

  Biomechanics

  Life Sciences

  Clinical Development

  Embryonic Stem Cells

  PCR

  Confocal Microscopy

  Mouse Models

  HIP/RPL29 down-regulation accompanies terminal chondrocyte differentiation.

  AJ Brown

  HIP is a heparin/heparan sulfate (Hp/HS) binding protein identical to ribosomal protein L29 that displays diverse biological functions. There is strong evidence that abnormal expression and quantitative deficiencies of essential molecules such as extracellular matrix (ECM) proteins and ribosomal proteins can seriously impair embryonic development. As observed for HS-bearing molecules

  high levels of HIP/RPL29 are found in proliferating chondrocytic precursors and chondrocytes of developing growth plate. Here

  we demonstrate both in vitro and in developing mouse embryos that HIP/RPL29 is down-regulated in terminally differentiated chondrocytes corresponding to the late hypertrophic zone of the growth plate. Because cartilage serves as a template for endochondral bone formation

  we hypothesize that the presence of HIP/RPL29 during early chondrogenesis is essential for normal skeletal growth and patterning. In particular

  we believe that HIP/RPL29 expression is required to maintain proliferation of chondrocytes and avoid skeletal shortening. Increasing evidence suggests that multifunctional ribosomal proteins of eukaryotic cells are important regulators of cell growth and differentiation

  not simply structural parts of translational machinery. To investigate the role of HIP/RPL29 normal expression during cartilage formation

  we designed a ribozyme-mediated knock-down approach to partially down-regulate HIP/RPL29 expression in the mouse embryonic skin fibroblast cell line C3H/10T (1/2). This technology permitted us to avoid the insufficient expression associated with more severe consequences

  such as lethality

  and provided advantages similar to those obtained with mutations generating hypomorphic phenotypes. Our results show that partial reduction of HIP/RPL29 levels accelerates differentiation of C3H/10T(1/2) into cartilage-like cells. In conclusion

  our data indicate that HIP/RPL29 constitutes an important novel regulator of chondrocytic growth and differentiation.

  HIP/RPL29 down-regulation accompanies terminal chondrocyte differentiation.

  Perlecan-containing pericellular matrix regulates solute transport and mechanosensing within the osteocyte lacunar-canalicular system

  Mary C. Farach-Carson

  Xinqiao Jia

  Weidong Yang

  Amit Jha

  Padma Srinivasan

  Injectable perlecan domain 1-hyaluronan microgels potentiate the cartilage repair effect of BMP2 in a murine model of early osteoarthritis

  Perlecan

  a heparan sulfate proteoglycan

  acts as a mechanical sensor for bone to detect external loading. Deficiency of perlecan increases the risk of osteoporosis in patients with Schwartz-Jampel Syndrome (SJS) and attenuates loading-induced bone formation in perlecan deficient mice (Hypo). Considering that intracellular calcium [Ca2+]i is an ubiquitous messenger controlling numerous cellular processes including mechanotransduction

  we hypothesized that perlecan deficiency impairs bone's calcium signaling in response to loading. To test this

  we performed real-time [Ca2+]i imaging on in situ osteocytes of adult murine tibiae under cyclic loading (8N). Relative to wild type (WT)

  Hypo osteocytes showed decreases in the overall [Ca2+]i response rate (-58%)

  calcium peaks (-33%)

  cells with multiple peaks (-53%)

  peak magnitude (-6.8%)

  and recovery speed to baseline (-23%). RNA sequencing and pathway analysis of tibiae from mice subjected to one or seven days of unilateral loading demonstrated that perlecan deficiency significantly suppressed the calcium signaling

  ECM-receptor interaction

  and focal adhesion pathways following repetitive loading. Defects in the endoplasmic reticulum (ER) calcium cycling regulators such as Ryr1/ryanodine receptors and Atp2a1/Serca1 calcium pumps were identified in Hypo bones. Taken together

  impaired calcium signaling may contribute to bone's reduced anabolic response to loading

  underlying the osteoporosis risk for the SJS patients.

  Perlecan/Hspg2 deficiency impairs bone's calcium signaling and associated transcriptome in response to mechanical loading.

  Trabecular Bone Deficit and Enhanced Anabolic Response to Re-Ambulation after Disuse in Perlecan-Deficient Skeleton.

  Inhibition of T-Type Voltage Sensitive Calcium Channel Reduces Load-Induced OA in Mice and Suppresses the Catabolic Effect of Bone Mechanical Stress on Chondrocytes

  Erica Selva

  William Thompson

  Padma Srinivasan

  Kerry Falgowski

  Sarah McCoy

  Serum xylosyltransferase 1 level increases during early posttraumatic osteoarthritis in mice with high bone forming potential

  Randy Duncan

  Mary (Cindy) Farach-Carsonran

  Perlecan/Hspg2 deficiency alters the pericellular space of the lacunocanalicular system surrounding osteocytic processes in cortical bone.

  MD Anderson Cancer Center

  The University of Texas Health Science Center at Houston (UTHealth) School of Dentistry

  University of Delaware

  Widener University

  Newark

  Teaching

  Academic Advising

  Mentoring

  Leading Research Projects

  Publishing in Peer-Reviewed Journals

  Serving as Peer-Reviewer for various Scientific Journals.

  Assistant Professor

  University of Delaware

  Molecular Genetics

  MD Anderson Cancer Center

  Widener University

  Chester

  Pennsylvania

  Assistant Teaching Professor of Biology

  Newark

  Mentoring Graduate and Undergraduate Students

  Leading Research Projects

  Publishing in Peer-Reviewed Journals

  Serving as Peer-Reviewer for various Scientific Journals.

  Research Assistant Professor

  University of Delaware

  Transgenic Research

  University of Delaware

  Post Doctoral Research

  Skeletal Biology

  The University of Texas Health Science Center at Houston (UTHealth) School of Dentistry