Academic Appointments

Professional Education

  • PhD, California Institute of Technology, Biology (2005)

Research & Scholarship

Clinical Trials

  • Grafting of Epidermolysis Bullosa Wounds Using Cultured Revertant Autologous Keratinocytes Not Recruiting

    The term epidermolysis bullosa (EB) is used to describe a group of genetic skin diseases associated with skin weakness, blisters, and chronic wounds. "Revertant mosaicism" means that there are two genetically different populations of cells due to spontaneous mutations. Some EB patients have normal, non-fragile skin patches which may be areas of revertant mosaicism. In the revertant areas, the proteins function normally, like non-EB skin. In this study, we plan to culture cells from the revertant areas and graft them on to the wounded areas.

    Stanford is currently not accepting patients for this trial. For more information, please contact Emily S Gorell, MS, 650-721-7166.

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Journal Articles

  • Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa SCIENCE TRANSLATIONAL MEDICINE Sebastiano, V., Zhen, H. H., Derafshi, B. H., Bashkirova, E., Melo, S. P., Wang, P., Leung, T. L., Siprashvili, Z., Tichy, A., Li, J., Ameen, M., Hawkins, J., Lee, S., Li, L., Schwertschkow, A., Bauer, G., Lisowski, L., Kay, M. A., Kim, S. K., Lane, A. T., Wernig, M., Oro, A. E. 2014; 6 (264)
  • An open-label study to evaluate sildenafil for the treatment of lymphatic malformations JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Danial, C., Tichy, A. L., Tariq, U., Swetman, G. L., Khuu, P., Leung, T. H., Benjamin, L., Teng, J., Vasanawala, S. S., Lane, A. T. 2014; 70 (6): 1050-1057


    Lymphatic malformations can be challenging to treat. Mainstay interventions including surgery and sclerotherapy are invasive and can result in local recurrence and complications.We sought to assess the effect of 20 weeks of oral sildenafil on reducing lymphatic malformation volume and symptoms in children.Seven children (4 boys, 3 girls; ages 13-85 months) with lymphatic malformations were given oral sildenafil for 20 weeks in this open-label study. The volume of the lymphatic malformation was calculated blindly using magnetic resonance imaging performed before and after 20 weeks of sildenafil. Lymphatic malformations were assessed clinically on weeks 4, 12, 20, and 32. Both the physician and parents evaluated the lymphatic malformation in comparison with baseline.Four subjects had a lymphatic malformation volume decrease (1.0%-31.7%). In 2 subjects, despite a lymphatic malformation volume increase (1.1%-3.7%), clinical improvement was noted while on sildenafil. One subject had a 29.6% increase in lymphatic malformation volume and no therapeutic response. Lymphatic malformations of all 6 subjects who experienced a therapeutic response on sildenafil softened and became easily compressible. Adverse events were minimal.A randomized controlled trial will be necessary to verify the effects of sildenafil on lymphatic malformations.Sildenafil can reduce lymphatic malformation volume and symptoms in some children.

    View details for DOI 10.1016/j.jaad.2014.02.005

    View details for Web of Science ID 000336030400023

    View details for PubMedID 24656411

  • Topical hypochlorite ameliorates NF-kappa B-mediated skin diseases in mice JOURNAL OF CLINICAL INVESTIGATION Leung, T. H., Zhang, L. F., Wang, J., Ning, S., Knox, S. J., Kim, S. K. 2013; 123 (12): 5361-5370


    Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-κB-dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-κB kinase (IKK), a key regulator of NF-κB activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-κB reporter mice, topical HOCl reduced LPS-induced NF-κB signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-κB-driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-κB-dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-κB-mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims.

    View details for DOI 10.1172/JCI70895

    View details for Web of Science ID 000327826100039

    View details for PubMedID 24231355

  • Achieving stability of lipopolysaccharide-induced NF-kappa B activation SCIENCE Covert, M. W., Leung, T. H., Gaston, J. E., Baltimore, D. 2005; 309 (5742): 1854-1857


    The activation dynamics of the transcription factor NF-kappaB exhibit damped oscillatory behavior when cells are stimulated by tumor necrosis factor-alpha (TNFalpha) but stable behavior when stimulated by lipopolysaccharide (LPS). LPS binding to Toll-like receptor 4 (TLR4) causes activation of NF-kappaB that requires two downstream pathways, each of which when isolated exhibits damped oscillatory behavior. Computational modeling of the two TLR4-dependent signaling pathways suggests that one pathway requires a time delay to establish early anti-phase activation of NF-kappaB by the two pathways. The MyD88-independent pathway required Inferon regulatory factor 3-dependent expression of TNFalpha to activate NF-kappaB, and the time required for TNFalpha synthesis established the delay.

    View details for DOI 10.1126/science.1112304

    View details for Web of Science ID 000231989500049

    View details for PubMedID 16166516

  • One nucleotide in a kappa B site can determine cofactor specificity for NF-kappa B dimers CELL Leung, T. H., Hoffmann, A., Baltimore, D. 2004; 118 (4): 453-464


    The transcription factor NF-kappaB regulates a wide variety of genes involved in multiple processes. Although the apparent consensus sequence of DNA binding sites for NF-kappaB (kappaB sites) is very broad, the sites active in any one gene show remarkable evolutionary stability. Using a lentivirus-based methodology for implantation of gene regulatory sequences we show that for genes with two kappaB sites, both are required for activity. Swapping sites between kappaB-dependent genes altered NF-kappaB dimer specificity of the promoters and revealed that two kappaB sites can function together as a module to regulate gene activation. Further, although the sequence of the kappaB site is important for determining kappaB family member specificity, rather than determining the ability of a particular dimer to bind effectively, the sequence affects which coactivators will form productive interactions with the bound NF-kappaB dimer. This suggests that binding sites may impart a specific configuration to bound transcription factors.

    View details for Web of Science ID 000223650900008

    View details for PubMedID 15315758

  • Genetic analysis of NF-kappa B/Rel transcription factors defines functional specificities EMBO JOURNAL Hoffmann, A., Leung, T. H., Baltimore, D. 2003; 22 (20): 5530-5539


    The NF-kappaB transcription factors consist of dimeric proteins of the Rel homology family. They activate many promoters containing highly divergent kappaB-site sequences. We have generated cell lines lacking individual and multiple NF-kappaB proteins and used them to establish interactions between components of the NF-kappaB-IkappaB signaling system. Functional compensation within the family of dimers was evident in knockout cell lines. Analysis of transiently transfected genes gave an impression of promiscuity that was not borne out by analysis of endogenous genes. Using TNFalpha as an inducer, a panel of endogenous genes showed a wide range of subunit specificities as well as highly variable kinetics of induction. Comparing the function and subunit specificity of genes with the sequence of the kappaB DNA-binding site we found little correlation, indicating that NF-kappaB family member specificity for endogenous promoters is not solely encoded by the kappaB site sequence itself.

    View details for Web of Science ID 000186014200020

    View details for PubMedID 14532125

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