Molecular Medicine

In this laboratory, genomic tools such as transcriptional profiling and next generation sequencing are used to identify disease-specific gene markers for common skin diseases such as melanoma, skin lymphoma, vitiligo and hyperhidrosis. These markers are then evaluated for their significance as diagnostic markers or therapeutic targets.  The current research projects include:

  1. Metastatic melanoma:
    Novel extracellular matrix molecules have been identified from metastatic melanoma tissues and cultured cell lines, including collagen-triple-helix-repeat containing protein 1 (CTHRC1) and alpha-1 antichymotrypsin (ACT1). Using in vitro and in vivo models, the contribution of these proteins to melanoma metastasis and mortality is being studied. Novel therapeutic strategies and evaluated to target these molecules.
  2. Mechanism of melanocyte cell death in vitiligo:
    Vitiligo is the most common depigmentation disease of the skin that affects approximately 1.5% of population worldwide. The mechanism of pathogenesis is unknown. Genomic markers identified in this lab highlight the importance of both autoimmunity and melanocyte development in this disease. The current focus is on the role of NK T cells and tissue microenvironment in the death of melanocytes in this disease.
  3. Cutaneous T cell lymphoma and Sezary syndrome:
    Sezary syndrome is an aggressive form of skin T cell lymphoma that has high mortality. The malignant cells in this disease, the Sezary cells have been purified and found to contain unique molecular markers. These markers, including T-plastin and SATB1, are studied for their diagnostic value and functional significance in malignant transformation of T lymphocytes.
  4. Primary focal hyperhidrosis:
    Primary focal hyperhidrosis is characterized by uncontrollable perspiration of hands, feet and the underarms. Affecting about 5% of the population worldwide, this condition frequently causes severe negative impact on the psychosocial wellbeing of the affected children and adults. Preliminary research from this laboratory suggests that this condition is an autosomal dominantly inherited disease with manifestations in the skin and in the central nervous system. We are interested in building a clinical database with banking of the blood samples to isolate the gene mutations or polymorphisms that are associated with the development of this disease. The goal is to find a cure for this common genetic condition.

Principle Investigator

Youwen Zhou, MD, PhD

Lab Location

Vancouver General Hospital Research Pavilion, Room 490

Visiting Scientist

Yan Wu, MD

Research Fellow

Yuanjie Huang, MD, PhD

Staff

Mingwan Su, PhD (Research Scientist)

Gigi Leung, BS (Technician)

Students

  • Sherry Yang (PhD student)
  • Vibudh Agrawal (Master Student)
  • Qianli Yang (PhD Student)

Major Investigative Technologies Utilized

  • Cell culture
  • Tissue banking
  • Immunohistochemistry
  • In situ hybridization
  • RNA sequencing
  • Single Cell sequencing
  • Computer aided drug design
  • Viral vector transduction
  • Peptide interference
  • Animal models

Recent Publications

  1. Wang, Y, Jiang, X, Su, M, and Zhou, Y. SATB1 Suppression Regulates Sezary cell apoptosis by modulating FasL expression. Blood, 2010 (In press)
  2. Quan, C, Ren, Y, Xiang, L, Sun, L, et al, Zhou, Y, and Zhang X-J. Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC. Nature Genetics, 2010. 42: 614-8
  3. Wang, Y, Jiang, H, Dai, et al and Zhou, Y. Alpha 1 antichymotrypsin is aberrantly expressed during melanoma progression and predicts poor survival for patients with metastatic melanoma. Pigment Cell Mel Res 2010; 23:575-8