|
Skin Cancer Biology Laboratory
- The Skin Cancer Biology Laboratory
is a world-class centre with the main
focus on molecular biology and genetics
of human melanoma cancer research.
- It is located in Jack Bell Research
Centre, Vancouver General Hospital.
- This laboratory is dedicated to
understanding the molecular mechanisms
behind the
development of melanoma.
- To date researchers in this laboratory
have had success in identifying several
new target molecules and genes for
treating malignant melanoma.
Background
- Melanoma is a life-threatening
skin cancer. Each year, 132,000 cases
of human melanoma are diagnosed. There
will be an estimated 5,000 new melanoma
cases and 940 melanoma-related deaths
in Canada 2009, according to the Canadian
Cancer Society.
- In some parts of the
world, especially among Western countries,
its incidence
in Caucasian populations has increased
faster than any other malignancy during
the last 20 years.
- Melanoma is an invasive cancer,
which metastasizes rapidly to other
organs,
and it is very resistant to conventional
therapies. Patients with metastatic
melanoma can only survive for 6–8.5
months on average.
- Well-defined risk
factors for melanoma
include dysplastic nevi, many ordinary
moles, fair skin, personal history
of melanoma or skin cancer, family history
of melanoma, weakened immune system,
blistering sunburns and ultraviolet radiation.
Research Foci
- Aberrant expression of tumor
suppressors / oncogenes in human melanoma.
- Role of tumor suppressors/oncogenes
in melanoma tumorigenesis and progression.
- Metastasis suppressors in melanoma
invasion and metastasis.
- DNA repair
impairment and genetic instability
in human melanoma.
- Response of melanoma
cells to environmental carcinogenetic
factors.
• Sustained angiogenesis and melanoma progression.
- Prognostic significance
and therapeutic biomarkers in human melanoma.
Research Goals
- Identifying the biomarkers involved
in melanoma initiation and progression.
- Revealing the molecular mechanisms
through which tumor suppressors / oncogenes
modulate
the biological behaviour of melanoma
cells in vitro.
- Clarifying the role
of tumor suppressors/oncogenes in melanoma
development and growth
in vivo.
- Establishing ideal set of biomarkers
for melanoma early diagnosis and accurate
prognosis.
- Developing novel therapeutic
strategy and improving melanoma patient
survival.
Research Approach
- The cancer biology lab has combined
in vivo and in vitro experimental approaches
in order to gain a better understanding
of molecular and cellular biology of
melanoma cancer.
- Tissue microarray technology is
used to look for new powerful markers
for
prognostic analysis of melanoma patients’ survival.
For these types of studies we have
established a closed partnership with
Department
of Pathology at VGH.
- Creation of knockdown
or overexpression mouse models of candidate
genes is
one of our major in vivo strategies to deduce
the functions as well as mechanisms
by which any specific gene of interest contributes
to cancer progression or suppression.
- Various molecular biology methods
such as recombinant DNA technology,
directed
mutagenesis, immunohistochemistry,
western blot, co-immunoprecipitation, Real Time-PCR,
and Fluorescence Activated Cell Sorting
are harnessed in this lab to further
study the detailed mechanisms of function
for genes of interest in vitro.
- CAT
assay, luciferase assay and slot blot
are used to examine the role of
candidate genes in regulating the ability
of the cells to repair DNA damages
upon UV irradiation or exposure to genotoxic
agents.
- Different techniques such as
wound healing, Boyden chamber and zymography
assays
along with in vivo tumorigenesis assay
are used to test for the role of candidate
genes in migration, invasion, and metastasis
of melanoma cells.
- HUVEC, ELISA and
plug formation assays are used to study
the role of candidate
genes in promoting the ability of tumor
cells to form blood vessel, which are
an important step in metastasis.
- Cancer
biology lab also has a broad facility
for cell and tissue culture with
numerous primary and skin cancer cell
lines.
Achievements
- The Cancer Biology lab is one
of the world leading laboratories in
studying the biological functions of
INhibitor of Growth (ING) family tumor
suppressors.
- Our team has discovered
several mechanisms by which the ING
proteins exert their
functions in tumor suppression either
through augmenting the ability of the
cell to repair DNA damages or suppressing
the illegitimate cell proliferation,
invasion or angiogenesis.
- We have had
a considerable contribution to the
understanding of the mechanisms
of functions of NQO1, ILK, NF-?B and
PUMA genes in melanoma cancer biology.
- This
laboratory has succeeded in discovering
several markers for initiation and/or
progression of melanoma cancer.
- The
investigators in this lab have received
grant awards from the Canadian Institutes
of Health Research (CIHR), National
Cancer Institute of Canada (NCIC) Canadian Dermatology
Foundation (CDF), Cancer Research
Society (CRS), Michael Smith Foundation
for
Health Research (MSFHR), National Science and
Engineering Research Council (NSERC)
and Canadian Melanoma Foundation.
Who We Are
Dr. Gang Li, Director, Skin
Cancer Biology Laboratory
- A world-renowned scientist studying
the molecular mechanisms of skin cancer
development.
Dr. Vincent Ho, Head, Dermatology/Oncology, BC Cancer Agency
- An
expert in skin cancer treatment and clinical
trials.
Dr. Marco Garate, Research Associate
- An
expert in protein biochemistry, cellular
and molecular biology.
- Research leader
on protein interaction, degradation
and signal transduction
in melanoma cells.
Dr. GuangDi Chen, Postdoctoral
fellow
- Studying
the degradation pathway of the tumor
suppressor ING3 in melanoma
cells.
- Investigating the functions
of tumor suppressor F-box proteins
in human melanoma.
Dr. Bo Wang, Postdoctoral fellow
- Investigating
the inhibitory role of ING3 (inhibitor
of growth family
member)
in skin tumorigenesis.
Dr. Aijaz Wani, Postdoctoral
fellow
- Studying
the role integrin-linkd kinase and interleukin-6
in melanoma
angiogenesis.
Dr Jin Bai, Postdoctoral
fellow
- Studying
the mechanisms of cancer invasion and
metastasis.
- Identifying prognostic
markers for cancer patients.
Dr Zhizhong Zhang, Postdoctoral
fellow
- Studying
the genetic variation of RUNX3 and the
risk of melanoma.
Ronald Wong, PhD candidate
- Studying
the role of the tumor suppressor ING1b
in genomic stability upon replication
stress.
Jun Li, PhD candidate
- Studying
the role of tumor suppressor-ING4 in
melanoma tumorigenesis and progression.
Yabin Cheng, PhD student
- Identifying prognostic markets and
therapeutic targets for melanoma.
Seyed Mehdi Jafarnejad, PhD
student
- Studying the involvement of cell
cycle checkpoint pathways in regulation
of
Translesion DNA Synthesis (TLS).
Brad Piche, PhD student
- Investigating the role of ING tumor
suppressors in nucleotide excision
repair
Hanyang Lin, MSc candidate
- Studying
the role of SWI/SNF chromatin remodelling
complex in human melanoma
tumorigenesis, progression, and nucleotide
excision repair.
|
