
Yiumo Michael Chan
AnnJi Pharmaceutical Co. Ltd, TaiwanTitle: Androgen receptor, oxidative stress and inflammation at the crossroads of skin diseases
Abstract
Skin represents one of the largest
organs in humans and is constantly under the insult of oxidative stress and
inflammation. Although many inflammatory and autoimmune skin diseases can be
managed by immunosuppressants and corticosteroids, the long-term use remains a
major safety concern in the medical practice. Here, we present evidence that a
class of non-steroid compounds, known as Nrf2 (nuclear factor erythroid
2-related factor 2) activators can be developed to treat different skin
diseases associated with increased oxidant stress and inflammatory responses.
Nrf2 is a well characterized master transcription factor to regulate cellular
antioxidant response. These novel compounds were designed based on structural
modifications of the natural product, curcumin. In additional to inducing
robust antioxidant response through Nrf2, our in vitro studies demonstrated
that these compounds have additional unique properties of suppressing
proinflammatory cytokines and enhancing the degradation of androgen receptor, possibly
through proteasome- and heat shock protein-mediated pathways. These compounds
were developed into different formulations for both oral and topical
administrations. The oral formulation is currently at the early clinical phase
for treatment of a rare poly-Q disease known as spinal and bulbar muscular
atrophy whereas the topical formulation has completed a global Phase 2 clinical
trial of acne vulgaris. Our preclinical studies in cell and animal models have
supported the therapeutic potential of these novel Nrf2 activators in different
skin disease models, such as keloid. As a result, this class of novel Nrf2
activators could be promising therapeutic agents to treat in treating a variety
of skin conditions, including androgen-associated skin diseases, inflammatory
skin diseases, wound healing, hair loss, and skin aging.
Biography
Yiumo Michael Chan’s research
areas include rare diseases research and drug development of small molecules.
Dr. Chan received his B.Sc. and Ph.D. degrees from the University of Chicago
and completed his post-doctoral training at Harvard Medical School. Dr. Chan
has extensive research experience in academia and held a faculty position at
Geisinger Medical Center, PA. He is a scientific leader in rare and
neuromuscular diseases with a proven record in publication and discovery,
including the identification of the genetic basis of Weber-Cockayne
epidermolysis bullosa simplex. Dr. Chan also serves several scientific advisory
boards for different patient organizations of rare diseases. In industry, Dr.
Chan has demonstrated a successful track record in drug development of small
molecules. He was responsible for translational programs in neuromuscular and
neurodevelopmental diseases at Ultragenyx, CA, including the GNE Myopathy
program which advanced from preclinical stage to Phase III clinical trial. Dr.
Chan is currently the Vice President of Research and Translational Medicine at
AnnJi Pharmaceutical, a clinical stage biopharmaceutical company specializing
in development of novel treatments for neglected diseases in neurology and
dermatology. He has led more than 6 Phase I/II clinical studies for common and
rare skin diseases.