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@ U S T . H K
may play a role in cancer progression
by silencing ERVs and in turn keeping
cancer cells alive.
Following confirmation of the function of SETDB1 in
melanoma through experiments, including analyses of
ERVs, Prof Leung’s research will use the high-throughput
and efficient system he has devised to screen for
potential drugs that inhibit this protein. The findings
will also provide insight into other cancers.
This type of epigenomic research has only recently become
feasible due to the advancement
in DNA sequencing technologies.
Specialized equipment, for
example the DNA sequencers that
Prof Leung needs to carry out
his work, is available in-house
at the University’s Biosciences
Central Research Facility, helping
HKUST life scientists to stay at the
leading edge.
In addition, Prof Leung
is heading the Hong Kong
Epigenomics Project, which draws
together 15 groups from five
institutions across the city, and
has been elected a member of the
International Human Epigenome
Consortium. Data generated will be
made publicly available allowing
researchers around the world to
use it.
Prof Leung has published in
Nature,
Proceedings of the National
Academy of Sciences
(
PNAS
),
and
Cell Stem Cell,
among others.
For biologist Prof Danny Leung,
bringing light to the “dark” side
of the genome could prove to be
a key factor in finding out what goes wrong
in cells to cause cancer and other human diseases. “All our
building blocks are coded in our genes, yet this only represents
2% of the genome, which means 98% is non-coding. These
parts have very important functions in normal biological
processes but our knowledge of how they are controlled is
limited. I like to call it the dark matter of the genome!”
Prof Leung’s focus is on greater understanding of the
epigenome, the layer on top of DNA that decides which pieces of
DNA get activated or repressed, how epigenetic modifications
of non-coding DNA are utilized in cancers and whether they
facilitate cancer cells to stay alive. In particular, he seeks to
elucidate the role of endogenous retroviruses (ERVs) in
modulating gene transcription and the epigenetic mechanisms
that silence these potentially harmful sequences. Such viruses
make up 8% of the human genome, a significant amount.
They have become part of our genome through evolution and
have the capacity to affect how our genes are controlled.
Prof Leung has been working in this cutting-edge
area of life science since his PhD at the University of British
Columbia. Prior to joining HKUST in 2015, he had managed
a branch of the US National Institutes of Health Roadmap
Epigenomics Project. Recently, he received a 2017 Croucher
Innovation Award, granted to a select group of rising star
scientists from universities in Hong Kong to support their
research over five years.
One major finding has shown that repressed harmful DNA
sequences were reactivated by depleting the SETDB1 enzyme,
resulting in the death of mouse embryonic stem cells. These
mouse cells share commonalities with human cancer cells,
such as melanoma, the most malignant type of skin cancer and
one that is on the rise. The discovery suggests that SETDB1
The ‘dark’ matter of
the genome has
been largely ignored
until recently. Long
thought to be junk,
it is now clear that
it isn’t
PROF DANNY LEUNG
Assistant Professor
of Life Science
ILLUMINATING
THE EPIGENOME
