chemistry-2019-keynote

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May 13-14, 2019 | Prague, Czech Republic
Chemistry and Medicinal Chemistry
9th World Congress on
Page 52
Asian Journal of Biomedical and Pharmaceutical Sciences | Volume 9 ISSN: 2249-622X
Jan-Growth Chang
China Medicine University Hospital, Taiwan
Modulating of RNA Alternative Splicing for the treatment of Cancer
and Genetic Diseases
RNA alternative splicing (AS) is a regulatory mechanism of
gene expression that allows cells to generate more than
one mRNA species from a single gene. AS can produce mRNAs
which differ in their untranslated regions or coding area
through exon skipping, mutually exclusive exons, the use of
AS sites, and introns retention. There difference may influence
mRNA stability, localization, or translation. AS may contribute
to cell differentiation and lineage determination, tissue-
identity acquisitionandmaintenance, andorgandevelopment.
AS is highly regulated, disturbance of AS machinery leads to
mis-splicing, and may result in a range of diseases including
cancer, genetic diseases and neurodegenerative disorders.
Understanding of the mechanism of AS result in the disease is
very important for designing effective therapeutic strategies.
ThespatiotemporalchangesofASaregovernedbycombination
of cis-regulatory elements and cognate trans-acting factors,
which promote or inhibit spliceosome assembly. AS is also
controlled by coordinated interactions with other regulatory
layers, including transcription and chromatin. Moreover, post-
translational and signaling pathways influence AS through
different mechanisms, such as by altering the function and/or
localization of key splicing regulators. This extensive crosstalk
between gene regulatory layers including dynamic spatial,
physical and temporal organizational properties of the cell
nucleus, and further emphasizes the importance of developing
a multidimensional understanding of AS, and also provides a
theoretical basis of drug design for the treatment of AS-relate
diseases and cancer.
To interrogate the treatment of AS-related diseases and
cancer, we have developed cell line-system to screen AS-
modulating small molecules and using animal model to test
their therapeutic effects. More than 500 compounds have
been screened, and we found several small molecules have
been found to affect the AS of the causing gene of SMA, Fibry’s
disease, and cancer including modulation of drug resistance.
From our results, we suggest that AS-related drugs may affect
different layers of AS regulatorymachinery, and this effect may
influence the therapeutic effect on the diseases. In this talk, I
am going to share our previous experience, and present our
recent research.
Speaker Biography
Jan-Growth Chang is an expert in the field of molecular diagnosis and
treatment of genetic disease and cancer. He was one of the pioneers of
the spinal muscular atrophy treatment using small molecules. He was
the pioneer to study the diuretic drug-amiloride and its derivatives on
RNA alternative splicing and explored their roles at the treatment of
cancer and genetic diseases. He has also developed many methods to
detect the genetic lesions of genetic diseases and cancer. He is author
of over 350 papers and owner of several patents. Now, he is Vice-
Superintendent of China Medicine University Hospital, and Director
of Department of Laboratory Medicine, Center for Precision Medicine,
and Epigenome Research center.
e:
Jan-Growth Chang, Asian J Biomed Pharmaceut Sci, Volume:9
DOI: 10.4066/2249-622X-C2-019
Notes: