Bio

Clinical Focus


  • General Surgery

Professional Education


  • Fellowship:Stanford University School of Medicine (2009) CA
  • Residency:Robert Wood Johnson Med School (2005)
  • Internship:Robert Wood Johnson Med School (1999)
  • Medical Education:Albert Einstein College of Medicine (1998) NY
  • Board Certification: General Surgery, American Board of Surgery
  • Board Certification: Surgical Critical Care, American Board of Surgery

Publications

Journal Articles


  • Unfolded Protein Response Regulation in Keloid Cells JOURNAL OF SURGICAL RESEARCH Butler, P. D., Wang, Z., Ly, D. P., Longaker, M. T., Koong, A. C., Yang, G. P. 2011; 167 (1): 151-157

    Abstract

    Keloids are a common form of pathologic wound healing characterized by excessive production of extracellular matrix. The unfolded protein response (UPR) is a cellular response to hypoxia, a component of the wound microenvironment, capable of protecting cells from the effects of over-accumulation of misfolded proteins. Since keloids have hypersecretion of extracellular matrix, we hypothesized that keloid fibroblasts (KFs) may have enhanced activation of the UPR compared with normal fibroblasts (NFs).KFs and NFs were placed in a hypoxia chamber for 0, 24, and 48h. We also used tunicamycin to specifically up-regulate the UPR. UPR activation was assayed by PCR for xbp-1 splicing and by immunoblotting with specific antibodies for the three UPR transducers. Nuclear localization of XBP-1 protein in KFs was confirmed by immunofluorescence.There is increased activation of XBP-1 protein in KFs compared with NFs following exposure to hypoxia. Pancreatic ER kinase (PERK) and ATF-6, two other pathways activated by the UPR, show comparable activation between KFs and NFs. We confirmed that there is enhanced activation of XBP-1 by demonstrating increased nuclear localization of XBP-1 using immunofluorescence.In contrast to our initial hypothesis that keloids would have broad activation of the UPR, we demonstrate here that there is a specific up-regulation of one facet of the UPR response. This may represent a specific molecular defect in KFs compared with NFs, and also suggests modulation of the UPR can be used in wound healing therapy.

    View details for DOI 10.1016/j.jss.2009.04.036

    View details for Web of Science ID 000288744100029

    View details for PubMedID 19631342

  • Engineered epidermal growth factor mutants with faster binding on-rates correlate with enhanced receptor activation FEBS LETTERS Lahti, J. L., Lui, B. H., Beck, S. E., Lee, S. S., Ly, D. P., Longaker, M. T., Yang, G. P., Cochran, J. R. 2011; 585 (8): 1135-1139

    Abstract

    Receptor tyrosine kinases (RTKs) regulate critical cell signaling pathways, yet the properties of their cognate ligands that influence receptor activation are not fully understood. There is great interest in parsing these complex ligand-receptor relationships using engineered proteins with altered binding properties. Here we focus on the interaction between two engineered epidermal growth factor (EGF) mutants and the EGF receptor (EGFR), a model member of the RTK superfamily. We found that EGF mutants with faster kinetic on-rates stimulate increased EGFR activation compared to wild-type EGF. These findings support previous predictions that faster association rates correlate with enhanced receptor activity.

    View details for DOI 10.1016/j.febslet.2011.03.044

    View details for Web of Science ID 000289505400004

    View details for PubMedID 21439278

  • Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271 NATURE Boiko, A. D., Razorenova, O. V., van de Rijn, M., Swetter, S. M., Johnson, D. L., Ly, D. P., Butler, P. D., Yang, G. P., Joshua, B., Kaplan, M. J., Longaker, M. T., Weissman, I. L. 2010; 466 (7302): 133-U155

    Abstract

    The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271(+) MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2(-/-)gammac(-/-) mice. The CD271(+) subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271(+) melanoma cells into engrafted human skin or bone in Rag2(-/-)gammac(-/-) mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271(-) cells. We also show that in mice, tumours derived from transplanted human CD271(+) melanoma cells were capable of metastatsis in vivo. CD271(+) melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage.

    View details for DOI 10.1038/nature09161

    View details for Web of Science ID 000279343800049

    View details for PubMedID 20596026

  • Use of organotypic coculture to study keloid biology AMERICAN JOURNAL OF SURGERY Butler, P. D., Ly, D. P., Longaker, M. T., Yang, G. P. 2008; 195 (2): 144-148

    Abstract

    Keloids are pathologic scars afflicting a large segment of our population and for which there is no definitive therapy. The lack of an animal model for keloid formation has hampered study. We developed an in vitro organotypic skin model to simulate normal keloid biology, which may allow us to study keloid formation without an animal model.Normal (NFs) and keloid (KFs) human fibroblasts were cultured in a collagen matrix to create a 3-dimensional dermal structure. Normal human keratinocytes (NKs) were cultured as a second layer on top and exposed to an air-fluid interface to allow differentiation into a mature keratinocyte layer. The organotypic skin was maintained for 28 days in Dulbecco's modified eagle medium with 10% fetal calf serum. Samples were collected, processed, sectioned, stained with hematoxylin and eosin, and then measured for qualitative analysis. alpha-smooth-muscle actin was also evaluated by immunoblotting.KF/NK organotypic skin showed increased collagen deposition, based on significantly denser collagen staining, with increased dermal thickness compared with NF/NK organotypic skin. We saw increased contracture in the KF/NK construct, and this correlated with increased organization of alpha-smooth-muscle actin fibers in the dermal layer of KF/NK organotypic skin compared with NF/NK skin.We have shown that coculture of KFs with keloid keratinocytes leads to an increased collagen production and dermal contracture compared with NFs and NKs, consistent with known keloid behavior. Given the lack of an animal model, we believe that organotypic skin culture can serve as a surrogate to study keloid formation.

    View details for DOI 10.1016/j.amjsurg.2007.10.003

    View details for Web of Science ID 000252598400002

    View details for PubMedID 18070722

Conference Proceedings


  • Early, Intermediate, and Late Effects of a Surgical Skills "Boot Camp" on an Objective Structured Assessment of Technical Skills: A Randomized Controlled Study Parent, R. J., Plerhoples, T. A., Long, E. E., Zimmer, D. M., Teshome, M., Mohr, C. J., Ly, D. P., Hernandez-Boussard, T., Curet, M. J., Dutta, S. ELSEVIER SCIENCE INC. 2010: 984-989

    Abstract

    Surgical interns enter residency with variable technical abilities and many feel unprepared to perform necessary procedures. We hypothesized that interns exposed to a preinternship intensive surgical skills curriculum would demonstrate improved competency over unexposed colleagues on a test of surgical skills and that this effect would persist throughout internship.We designed a 3-day intensive skills "boot camp" with simulation-based training on 10 topics. Interns were randomized to an intervention group (boot camp) or a control group (no boot camp). All interns completed a survey including demographic information, previous experience, and comfort with basic surgical skills. Both groups completed a clinical skills assessment focused on 4 topics: chest tube insertion, central line placement, wound closure, and the Fundamentals of Laparoscopic Surgery peg transfer task. We assessed both groups immediately (month 0), early postcurriculum (month 1), and late postcurriculum (month 6).Fifteen participants were in the intervention group and 13 were in the control group. Before boot camp, mean comfort levels were similar for the groups. All participants had minimal prior experience. Competency for chest tube insertion and central line placement were considerably higher for the boot camp group at months 0 and 1, although much of this difference disappeared by month 6. There was no substantial difference between the 2 groups in the Fundamentals of Laparoscopic Surgery peg transfer and wound closure skills.A surgical skills boot camp accelerates the learning curve for interns in basic surgical skills as measured by a technical skills examination for some skills, although these improvements diminished over time. This can augment traditional training and translate into fewer patient errors.

    View details for DOI 10.1016/j.jamcollsurg.2010.03.006

    View details for Web of Science ID 000278649100013

    View details for PubMedID 20510808

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