Bio

Professional Education


  • Bachelor of Arts, University of Cambridge (2002)
  • B of Medicine and B of Surgery, University of Cambridge (2005)
  • Master of Arts, University of Cambridge (2006)

Stanford Advisors


Publications

Journal Articles


  • TWIST1 Silencing Enhances In Vitro and In Vivo Osteogenic Differentiation of Human Adipose-Derived Stem Cells by Triggering Activation of BMP-ERK/FGF Signaling and TAZ Upregulation. Stem cells Quarto, N., Senarath-Yapa, K., Renda, A., Longaker, M. T. 2015; 33 (3): 833-847

    Abstract

    Mesenchymal stem cells (MSCs) show promise for cellular therapy and regenerative medicine. Human adipose tissue-derived stem cells (hASCs) represent an attractive source of seed cells in bone regeneration. How to effectively improve osteogenic differentiation of hASCs in the bone tissue engineering has become a very important question with profound translational implications. Numerous regulatory pathways dominate osteogenic differentiation of hASCs involving transcriptional factors and signaling molecules. However, how these factors combine with each other to regulate hASCs osteogenic differentiation still remains to be illustrated. The highly conserved developmental proteins TWIST play key roles for transcriptional regulation in mesenchymal cell lineages. This study investigates TWIST1 function in hASCs osteogenesis. Our results show that TWIST1 shRNA silencing increased the osteogenic potential of hASCs in vitro and their skeletal regenerative ability when applied in vivo. We demonstrate that the increased osteogenic capacity observed with TWIST1 knockdown in hASCs is mediated through endogenous activation of BMP and ERK/FGF signaling leading, in turn, to upregulation of TAZ, a transcriptional modulator of MSCs differentiation along the osteoblast lineage. Inhibition either of BMP or ERK/FGF signaling suppressed TAZ upregulation and the enhanced osteogenesis in shTWIST1 hASCs. Cosilencing of both TWIST1 and TAZ abrogated the effect elicited by TWIST1 knockdown thus, identifying TAZ as a downstream mediator through which TWIST1 knockdown enhanced osteogenic differentiation in hASCs. Our functional study contributes to a better knowledge of molecular mechanisms governing the osteogenic ability of hASCs, and highlights TWIST1 as a potential target to facilitate in vivo bone healing. Stem Cells 2015;33:833-847.

    View details for DOI 10.1002/stem.1907

    View details for PubMedID 25446627

  • Scarless wound healing: chasing the holy grail. Plastic and reconstructive surgery Walmsley, G. G., Maan, Z. N., Wong, V. W., Duscher, D., Hu, M. S., Zielins, E. R., Wearda, T., Muhonen, E., McArdle, A., Tevlin, R., Atashroo, D. A., Senarath-Yapa, K., Lorenz, H. P., Gurtner, G. C., Longaker, M. T. 2015; 135 (3): 907-917

    Abstract

    Over 100 million patients acquire scars in the industrialized world each year, primarily as a result of elective operations. Although undefined, the global incidence of scarring is even larger, extending to significant numbers of burn and other trauma-related wounds. Scars have the potential to exert a profound psychological and physical impact on the individual. Beyond aesthetic considerations and potential disfigurement, scarring can result in restriction of movement and reduced quality of life. The formation of a scar following skin injury is a consequence of wound healing occurring through reparative rather than regenerative mechanisms. In this article, the authors review the basic stages of wound healing; differences between adult and fetal wound healing; various mechanical, genetic, and pharmacologic strategies to reduce scarring; and the biology of skin stem/progenitor cells that may hold the key to scarless regeneration.

    View details for DOI 10.1097/PRS.0000000000000972

    View details for PubMedID 25719706

  • Identification and specification of the mouse skeletal stem cell. Cell Chan, C. K., Seo, E. Y., Chen, J. Y., Lo, D., McArdle, A., Sinha, R., Tevlin, R., Seita, J., Vincent-Tompkins, J., Wearda, T., Lu, W., Senarath-Yapa, K., Chung, M. T., Marecic, O., Tran, M., Yan, K. S., Upton, R., Walmsley, G. G., Lee, A. S., Sahoo, D., Kuo, C. J., Weissman, I. L., Longaker, M. T. 2015; 160 (1-2): 285-298

    Abstract

    How are skeletal tissues derived from skeletal stem cells? Here, we map bone, cartilage, and stromal development from a population of highly pure, postnatal skeletal stem cells (mouse skeletal stem cells, mSSCs) to their downstream progenitors of bone, cartilage, and stromal tissue. We then investigated the transcriptome of the stem/progenitor cells for unique gene-expression patterns that would indicate potential regulators of mSSC lineage commitment. We demonstrate that mSSC niche factors can be potent inducers of osteogenesis, and several specific combinations of recombinant mSSC niche factors can activate mSSC genetic programs inásitu, even in nonskeletal tissues, resulting in de novo formation of cartilage or bone and bone marrow stroma. Inducing mSSC formation with soluble factors and subsequently regulating the mSSC niche to specify its differentiation toward bone, cartilage, or stromal cells could represent a paradigm shift in the therapeutic regeneration of skeletal tissues.

    View details for DOI 10.1016/j.cell.2014.12.002

    View details for PubMedID 25594184

  • Epigenetic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hematopoietic niche formation. Blood Reinisch, A., Etchart, N., Thomas, D., Hofmann, N. A., Fruehwirth, M., Sinha, S., Chan, C. K., Senarath-Yapa, K., Seo, E., Wearda, T., Hartwig, U. F., Beham-Schmid, C., Trajanoski, S., Lin, Q., Wagner, W., Dullin, C., Alves, F., Andreeff, M., Weissman, I. L., Longaker, M. T., Schallmoser, K., Majeti, R., Strunk, D. 2015; 125 (2): 249-260

    Abstract

    In the last decade there has been a rapid expansion in clinical trials using mesenchymal stromal cells (MSCs) from a variety of tissues. However, despite similarities in morphology, immunophenotype and differentiation behavior in vitro, MSCs sourced from distinct tissues do not necessarily have equivalent biological properties. We performed a genome-wide methylation, transcription and in vivo evaluation of MSCs from human bone marrow (BM), white adipose tissue, umbilical cord and skin cultured in humanized media. Surprisingly, only BM-derived MSCs spontaneously formed a bone marrow cavity through a vascularized cartilage intermediate in vivo that was progressively replaced by hematopoietic tissue and bone. Only BM-derived MSCs exhibited a chondrogenic transcriptional program with hypomethylation and increased expression of RUNX3, RUNX2, BGLAP, MMP13 and ITGA10 consistent with a latent and primed skeletal developmental potential. The humanized MSC-derived microenvironment permitted homing and maintenance of long-term murine SLAM(+) hematopoietic stem cells (HSCs) as well as human CD34(+)/CD38(-)/CD90(+)/CD45RA(+) HSCs after cord blood transplantation. These studies underscore the profound differences in developmental potential between MSC sources independent of donor age with implications for their clinical use. We also demonstrate a tractable human niche model for studying homing and engraftment of human hematopoietic cells in normal and neoplastic states.

    View details for DOI 10.1182/blood-2014-04-572255

    View details for PubMedID 25406351

  • Assessment of viability of human fat injection into nude mice with micro-computed tomography. Journal of visualized experiments : JoVE Atashroo, D. A., Paik, K. J., Chung, M. T., McArdle, A., Senarath-Yapa, K., Zielins, E. R., Tevlin, R., Duldulao, C. R., Walmsley, G. G., Wearda, T., Marecic, O., Longaker, M. T., Wan, D. C. 2015

    Abstract

    Lipotransfer is a vital tool in the surgeon's armamentarium for the treatment of soft tissue deficits of throughout the body. Fat is the ideal soft tissue filler as it is readily available, easily obtained, inexpensive, and inherently biocompatible.(1) However, despite its burgeoning popularity, fat grafting is hampered by unpredictable results and variable graft survival, with published retention rates ranging anywhere from 10-80%. (1-3) To facilitate investigations on fat grafting, we have therefore developed an animal model that allows for real-time analysis of injected fat volume retention. Briefly, a small cut is made in the scalp of a CD-1 nude mouse and 200-400 Áláof processed lipoaspirate is placed over the skull. The scalp is chosen as the recipient site because of its absence of native subcutaneous fat, and because of the excellent background contrast provided by the calvarium, which aids in the analysis process. Micro-computed tomography (micro-CT) is used to scan the graft at baseline and every two weeks thereafter. The CT images are reconstructed, and an imaging software is used to quantify graft volumes. Traditionally, techniques to assess fat graft volume have necessitated euthanizing the study animal to provide just a single assessment of graft weight and volume by physical measurement ex vivo. Biochemical and histological comparisons have likewise required the study animal to be euthanized. This described imaging technique offers the advantage of visualizing and objectively quantifying volume at multiple time points after initial grafting without having to sacrifice the study animal. The technique is limited by the size of the graft able to be injected as larger grafts risk skin and fat necrosis. This method has utility for all studies evaluating fat graft viability and volume retention. It is particularly well-suited to providing a visual representation of fat grafts and following changes in volume over time.

    View details for DOI 10.3791/52217

    View details for PubMedID 25590561

  • Isolation and Enrichment of Human Adipose-derived Stromal Cells for Enhanced Osteogenesis. Journal of visualized experiments : JoVE Zielins, E. R., Tevlin, R., Hu, M. S., Chung, M. T., McArdle, A., Paik, K. J., Atashroo, D., Duldulao, C. R., Luan, A., Senarath-Yapa, K., Walmsley, G. G., Wearda, T., Longaker, M. T., Wan, D. C. 2015

    Abstract

    Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are considered the gold standard for stem cell-based tissue engineering applications. However, the process by which they must be harvested can be associated with significant donor site morbidity. In contrast, adipose-derived stromal cells (ASCs) are more readily abundant and more easily harvested, making them an appealing alternative to BM-MSCs. Like BM-MSCs, ASCs can differentiate into osteogenic lineage cells and can be used in tissue engineering applications, such as seeding onto scaffolds for use in craniofacial skeletal defects. ASCs are obtained from the stromal vascular fraction (SVF) of digested adipose tissue, which is a heterogeneous mixture of ASCs, vascular endothelial and mural cells, smooth muscle cells, pericytes, fibroblasts, and circulating cells. Flow cytometric analysis has shown that the surface marker profile for ASCs is similar to that for BM-MSCs. Despite several published reports establishing markers for the ASC phenotype, there is still a lack of consensus over profiles identifying osteoprogenitor cells in this heterogeneous population. This protocol describes how to isolate and use a subpopulation of ASCs with enhanced osteogenic capacity to repair critical-sized calvarial defects.

    View details for DOI 10.3791/52181

    View details for PubMedID 25650785

  • Wnts produced by Osterix-expressing osteolineage cells regulate their proliferation and differentiation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Tan, S. H., Senarath-Yapa, K., Chung, M. T., Longaker, M. T., Wu, J. Y., Nusse, R. 2014; 111 (49): E5262-E5271

    Abstract

    Wnt signaling is a critical regulator of bone development, but the identity and role of the Wnt-producing cells are still unclear. We addressed these questions through in situ hybridization, lineage tracing, and genetic experiments. First, we surveyed the expression of all 19 Wnt genes and Wnt target gene Axin2 in the neonatal mouse bone by in situ hybridization, and demonstrated-to our knowledge for the first time-that Osterix-expressing cells coexpress Wnt and Axin2. To track the behavior and cell fate of Axin2-expressing osteolineage cells, we performed lineage tracing and showed that they sustain bone formation over the long term. Finally, to examine the role of Wnts produced by Osterix-expressing cells, we inhibited Wnt secretion in vivo, and observed inappropriate differentiation, impaired proliferation, and diminished Wnt signaling response. Therefore, Osterix-expressing cells produce their own Wnts that in turn induce Wnt signaling response, thereby regulating their proliferation and differentiation.

    View details for DOI 10.1073/pnas.1420463111

    View details for Web of Science ID 000345921500004

    View details for PubMedID 25422448

  • Biomaterials for Craniofacial Bone Engineering JOURNAL OF DENTAL RESEARCH Tevlin, R., Mcardle, A., Atashroo, D., Walmsley, G. G., Senarath-Yapa, K., Zielins, E. R., Paik, K. J., Longaker, M. T., Wan, D. C. 2014; 93 (12): 1187-1195
  • Positive Selection for Bone Morphogenetic Protein Receptor Type-IB Promotes Differentiation and Specification of Human Adipose-Derived Stromal Cells Toward an Osteogenic Lineage TISSUE ENGINEERING PART A McArdle, A., Chung, M. T., Paik, K. J., Duldulao, C., Chan, C., Rennert, R., Walmsley, G. G., Senarath-Yapa, K., Hu, M., Seo, E., Lee, M., Wan, D. C., Longaker, M. T. 2014; 20 (21-22): 3031-3040
  • The role of stem cells in aesthetic surgery: fact or fiction? Plastic and reconstructive surgery McArdle, A., Senarath-Yapa, K., Walmsley, G. G., Hu, M., Atashroo, D. A., Tevlin, R., Zielins, E., Gurtner, G. C., Wan, D. C., Longaker, M. T. 2014; 134 (2): 193-200

    Abstract

    Stem cells are attractive candidates for the development of novel therapies, targeting indications that involve functional restoration of defective tissue. Although most stem cell therapies are new and highly experimental, there are clinics around the world that exploit vulnerable patients with the hope of offering supposed stem cell therapies, many of which operate without credible scientific merit, oversight, or other patient protection.We review the potential, as well as drawbacks, for incorporation of stem cells in cosmetic procedures. A review of FDA-approved indications and ongoing clinical trials with adipose stem cells is provided. Furthermore, a "snapshot" analysis of websites using the search terms "stem cell therapy" or "stem cell treatment" or "stem cell facelift" was performed.Despite the protective net cast by regulatory agencies such as the FDA and professional societies such as the American Society of Plastic Surgeons, we are witnessing worrying advertisements for procedures such as stem cell facelifts, stem cell breast augmentations, and even stem cell vaginal rejuvenation. The marketing and promotion of stem cell procedures in aesthetic surgery is not adequately supported by clinical evidence in the majority of cases.Stem cells offer tremendous potential, but the marketplace is saturated with unsubstantiated and sometimes fraudulent claims that may place patients at risk. With plastic surgeons at the forefront of stem cell-based regenerative medicine, it is critically important that we provide an example of a rigorous approach to research, data collection, and advertising of stem cell therapies.

    View details for DOI 10.1097/PRS.0000000000000404

    View details for PubMedID 24732654

  • Studies in fat grafting: part I. Effects of injection technique on in vitro fat viability and in vivo volume retention. Plastic and reconstructive surgery Chung, M. T., Paik, K. J., Atashroo, D. A., Hyun, J. S., McArdle, A., Senarath-Yapa, K., Zielins, E. R., Tevlin, R., Duldulao, C., Hu, M. S., Walmsley, G. G., Parisi-Amon, A., Momeni, A., Rimsa, J. R., Commons, G. W., Gurtner, G. C., Wan, D. C., Longaker, M. T. 2014; 134 (1): 29-38

    Abstract

    Fat grafting has become increasingly popular for the correction of soft tissue deficits at many sites throughout the body. Long-term outcomes, however, depend on delivery of fat in the least traumatic fashion to optimize viability of the transplanted tissue. In this study, we compare the biologic properties of fat following injection using two methods.Lipoaspiration samples were obtained from five female donors and cellular viability, proliferation, and lipolysis were evaluated following injection using either a modified Coleman technique or an automated, low shear device. Comparisons were made to minimally processed, uninjected fat. Volume retention was also measured over twelve weeks following injection of fat under the scalp of immunodeficient mice using either the modified Coleman technique or the Adipose Tissue Injector. Finally, fat grafts were analyzed histologically.Fat viability and cellular proliferation were both significantly greater with the Adipose Tissue Injector relative to injection with the modified Coleman technique. In contrast, significantly less lipolysis was noted using the automated device. In vivo fat volume retention was significantly greater than with the modified Coleman technique at 4, 6, 8, and 12 week time points. This corresponded with significantly greater histological scores for healthy fat and lower scores for injury following injection with the device.Biological properties of injected tissues reflect how disruptive and harmful techniques for placement of fat may be, and our in vitro and in vivo data both support the use of the automated, low shear devices compared to the modified Coleman technique.

    View details for DOI 10.1097/PRS.0000000000000290

    View details for PubMedID 24622574

  • Studies in Fat Grafting: Part I. Effects of Injection Technique on In Vitro Fat Viability and In Vivo Volume Retention PLASTIC AND RECONSTRUCTIVE SURGERY Chung, M. T., Paik, K. J., Atashroo, D. A., Hyun, J. S., McArdle, A., Senarath-Yapa, K., Zielins, E. R., Tevlin, R., Duldulao, C., Hu, M. S., Walmsley, G. G., Parisi-Amon, A., Momeni, A., Rimsa, J. R., Commons, G. W., Gurtner, G. C., Wan, D. C., Longaker, M. T. 2014; 134 (1): 29-38
  • Studies in Fat Grafting: Part II. Effects of Injection Mechanics on Material Properties of Fat PLASTIC AND RECONSTRUCTIVE SURGERY Atashroo, D., Raphel, J., Chung, M. T., Paik, K. J., Parisi-Amon, A., McArdle, A., Senarath-Yapa, K., Zielins, E. R., Tevlin, R., Duldulao, C., Walmsley, G. G., Hu, M. S., Momeni, A., Domecus, B., Rimsa, J. R., Greenberg, L., Gurtner, G. C., Longaker, M. T., Wan, D. C. 2014; 134 (1): 39-46
  • Adipose-Derived Stem Cells: A Review of Signaling Networks Governing Cell Fate and Regenerative Potential in the Context of Craniofacial and Long Bone Skeletal Repair INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Senarath-Yapa, K., McArdle, A., Renda, A., Longaker, M. T., Quarto, N. 2014; 15 (6): 9314-9330

    Abstract

    Improvements in medical care, nutrition and social care are resulting in a commendable change in world population demographics with an ever increasing skew towards an aging population. As the proportion of the world's population that is considered elderly increases, so does the incidence of osteodegenerative disease and the resultant burden on healthcare. The increasing demand coupled with the limitations of contemporary approaches, have provided the impetus to develop novel tissue regeneration therapies. The use of stem cells, with their potential for self-renewal and differentiation, is one potential solution. Adipose-derived stem cells (ASCs), which are relatively easy to harvest and readily available have emerged as an ideal candidate. In this review, we explore the potential for ASCs to provide tangible therapies for craniofacial and long bone skeletal defects, outline key signaling pathways that direct these cells and describe how the developmental signaling program may provide clues on how to guide these cells in vivo. This review also provides an overview of the importance of establishing an osteogenic microniche using appropriately customized scaffolds and delineates some of the key challenges that still need to be overcome for adult stem cell skeletal regenerative therapy to become a clinical reality.

    View details for DOI 10.3390/ijms15069314

    View details for Web of Science ID 000338639000009

  • Induced Pluripotent Stem Cells in Regenerative Medicine and Disease Modeling CURRENT STEM CELL RESEARCH & THERAPY Walmsley, G. G., Hyun, J., McArdle, A., Senarath-Yapa, K., Hu, M. S., Chung, M. T., Wong, V. W., Longaker, M. T., Wan, D. C. 2014; 9 (2): 73-81

    Abstract

    In 2006, Dr. Yamanaka created the induced pluripotent stem cell (iPSC) by reprogramming adult fibroblasts back to an immature, pluripotent state. Effectively bypassing the ethical constraints of human embryonic stem cells, iPSCs have expanded the horizons of regenerative medicine by offering a means to derive autologous patient-matched cells and tissues for clinical transplantation. However, persisting safety concerns must be addressed prior to their widespread clinical application. In this review, we discuss the history of iPSCs, derivation strategies, and current research involving gene therapy and disease modeling. We review the potential of iPSCs for improving a range of cell-based therapies and obstacles to their clinical implementation.

    View details for Web of Science ID 000331890000001

    View details for PubMedID 24359141

  • Wound healing: an update REGENERATIVE MEDICINE Zielins, E. R., Atashroo, D. A., Maan, Z. N., Duscher, D., Walmsley, G. G., Marecic, O., Hu, M., Senarath-Yapa, K., McArdle, A., Tevlin, R., Wearda, T., Paik, K. J., Duldulao, C., Hong, W. X., Gurtner, G. C., Longaker, M. T. 2014; 9 (6): 817-830

    View details for DOI 10.2217/RME.14.54

    View details for Web of Science ID 000345620600012

  • Osteoclast derivation from mouse bone marrow. Journal of visualized experiments : JoVE Tevlin, R., McArdle, A., Chan, C. K., Pluvinage, J., Walmsley, G. G., Wearda, T., Marecic, O., Hu, M. S., Paik, K. J., Senarath-Yapa, K., Atashroo, D. A., Zielins, E. R., Wan, D. C., Weissman, I. L., Longaker, M. T. 2014

    Abstract

    Osteoclasts are highly specialized cells that are derived from the monocyte/macrophage lineage of the bone marrow. Their unique ability to resorb both the organic and inorganic matrices of bone means that they play a key role in regulating skeletal remodeling. Together, osteoblasts and osteoclasts are responsible for the dynamic coupling process that involves both bone resorption and bone formation acting together to maintain the normal skeleton during health and disease. As the principal bone-resorbing cell in the body, changes in osteoclast differentiation or function can result in profound effects in the body. Diseases associated with altered osteoclast function can range in severity from lethal neonatal disease due to failure to form a marrow space for hematopoiesis, to more commonly observed pathologies such as osteoporosis, in which excessive osteoclastic bone resorption predisposes to fracture formation. An ability to isolate osteoclasts in high numbers in vitro has allowed for significant advances in the understanding of the bone remodeling cycle and has paved the way for the discovery of novel therapeutic strategies that combat these diseases. Here, we describe a protocol to isolate and cultivate osteoclasts from mouse bone marrow that will yield large numbers of osteoclasts.

    View details for DOI 10.3791/52056

    View details for PubMedID 25407120

  • Isolation of Human Adipose-Derived Stromal Cells Using Laser-Assisted Liposuction and Their Therapeutic Potential in Regenerative Medicine STEM CELLS TRANSLATIONAL MEDICINE Chung, M. T., Zimmermann, A. S., Paik, K. J., Morrison, S. D., Hyun, J. S., Lo, D. D., McArdle, A., Montoro, D. T., Walmsley, G. G., Senarath-Yapa, K., Sorkin, M., Rennert, R., Chen, H., Chung, A. S., Vistnes, D., Gurtner, G. C., Longaker, M. T., Wan, D. C. 2013; 2 (10): 808-817

    Abstract

    Harvesting adipose-derived stromal cells (ASCs) for tissue engineering is frequently done through liposuction. However, several different techniques exist. Although third-generation ultrasound-assisted liposuction has been shown to not have a negative effect on ASCs, the impact of laser-assisted liposuction on the quality and differentiation potential of ASCs has not been studied. Therefore, ASCs were harvested from laser-assisted lipoaspirate and suction-assisted lipoaspirate. Next, in vitro parameters of cell yield, cell viability and proliferation, surface marker phenotype, osteogenic differentiation, and adipogenic differentiation were performed. Finally, in vivo bone formation was assessed using a critical-sized cranial defect in athymic nude mice. Although ASCs isolated from suction-assisted lipoaspirate and laser-assisted lipoaspirate both successfully underwent osteogenic and adipogenic differentiation, the cell yield, viability, proliferation, and frequency of ASCs (CD34(+)CD31(-)CD45(-)) in the stromal vascular fraction were all significantly less with laser-assisted liposuction in vitro (p < .05). In vivo, quantification of osseous healing by micro-computed tomography revealed significantly more healing with ASCs isolated from suction-assisted lipoaspirate relative to laser-assisted lipoaspirate at the 4-, 6-, and 8-week time points (p < .05). Therefore, as laser-assisted liposuction appears to negatively impact the biology of ASCs, cell harvest using suction-assisted liposuction is preferable for tissue-engineering purposes.

    View details for DOI 10.5966/sctm.2012-0183

    View details for Web of Science ID 000325384600015

  • Commentary on the differential healing capacity of calvarial bone. journal of craniofacial surgery Lo, D. D., McArdle, A., Senarath-Yapa, K., Longaker, M. T. 2013; 24 (2): 344-345

    View details for DOI 10.1097/SCS.0b013e3182802256

    View details for PubMedID 23524689

  • Integration of Multiple Signaling Pathways Determines Differences in the Osteogenic Potential and Tissue Regeneration of Neural Crest-Derived and Mesoderm-Derived Calvarial Bone INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Senarath-Yapa, K., Li, S., Meyer, N. P., Longaker, M. T., Quarto, N. 2013; 14 (3): 5978-5997

    Abstract

    The mammalian skull vault, a product of a unique and tightly regulated evolutionary process, in which components of disparate embryonic origin are integrated, is an elegant model with which to study osteoblast biology. Our laboratory has demonstrated that this distinct embryonic origin of frontal and parietal bones confer differences in embryonic and postnatal osteogenic potential and skeletal regenerative capacity, with frontal neural crest derived osteoblasts benefitting from greater osteogenic potential. We outline how this model has been used to elucidate some of the molecular mechanisms which underlie these differences and place these findings into the context of our current understanding of the key, highly conserved, pathways which govern the osteoblast lineage including FGF, BMP, Wnt and TGF? signaling. Furthermore, we explore recent studies which have provided a tantalizing insight into way these pathways interact, with evidence accumulating for certain transcription factors, such as Runx2, acting as a nexus for cross-talk.

    View details for DOI 10.3390/ijms14035978

    View details for Web of Science ID 000316609800086

    View details for PubMedID 23502464

  • Discussion: A report of the ASPS Task Force on regenerative medicine: opportunities for plastic surgery. Plastic and reconstructive surgery McArdle, A., Lo, D. D., Hyun, J. S., Senarath-Yapa, K., Chung, M. T., Wan, D. C., Longaker, M. T. 2013; 131 (2): 400-403

    View details for DOI 10.1097/PRS.0b013e318278d88c

    View details for PubMedID 23358002

  • Craniosynostosis Molecular pathways and future pharmacologic therapy ORGANOGENESIS Senarath-Yapa, K., Chung, M. T., McArdle, A., Wong, V. W., Quarto, N., Longaker, M. T., Wan, D. C. 2012; 8 (4): 103-113

    View details for DOI 10.4161/org.23307

    View details for Web of Science ID 000314500600002

  • Craniosynostosis: Molecular pathways and future pharmacologic therapy. Organogenesis Senarath-Yapa, K., Chung, M. T., McArdle, A., Wong, V. W., Quarto, N., Longaker, M. T., Wan, D. C. 2012; 8 (4)

    Abstract

    Craniosynostosis describes the premature fusion of one or more cranial sutures and can lead to dramatic manifestations in terms of appearance and functional impairment. Contemporary approaches for this condition are primarily surgical and are associated with considerable morbidity and mortality. The additional post-operative problems of suture refusion and bony relapse may also necessitate repeated surgeries with their own attendant risks. Therefore, a need exists to not only optimize current strategies but also to develop novel biological therapies which could obviate the need for surgery and potentially treat or even prevent premature suture fusion. Clinical studies of patients with syndromic craniosynostosis have provided some useful insights into the important signaling pathways and molecular events guiding suture fate. Furthermore, the highly conserved nature of craniofacial development between humans and other species have permitted more focused and step-wise elucidation of the molecular underpinnings of craniosynostosis. This review will describe the clinical manifestations of craniosynostosis, reflect on our understanding of syndromic and non-syndromic craniosynostoses and outline the different approaches that have been adopted in our laboratory and elsewhere to better understand the pathogenesis of premature suture fusion. Finally, we will assess to what extent our improved understanding of the pathogenesis of craniosynostosis, achieved through laboratory-based and clinical studies, have made the possibility of a non-surgical pharmacological approach both realistic and tangible.

    View details for PubMedID 23249483

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