RESEARCH & PUBLICATIONS
Link to Richard's Google Scholar Profile
My primary research interest is in the field of bioinformatics, systems biology, and medical physics. I have also done work in the field of regenerative medicine during my undergraduate studies at the Hong Kong Polytechnic University with Dr. Xin Zhao. Please see below for a list of my research work.
DETERMINATION OF POTENTIAL WIDE-SPECTRUM CORONAVIRUS MRNA VACCINE CANDIDATES WITH STRUCTURAL BIOINFORMATICS
This paper is submitted as the course final project for BIOL 465: Structural Bioinformatics at the University of Waterloo.
The COVID-19 pandemic caused by the SARS-CoV-2 coronavirus has created chaos and placed significant burdens on the global health care system. With the threat of novel variants and species of coronaviruses emerging in the future and causing more epidemics, it is clear that the world needs a wide-spectrum mRNA vaccine that can protect people from various coronaviruses at the same time. As a first step in developing such a vaccine, this study utilized bioinformatic tools such as multiple sequence alignment, BLAST, protein structure prediction, and protein structure superposition to investigate structurally conserved proteins in coronaviruses to be used as mRNA vaccine candidates. It was found that the membrane (M) proteins of coronaviruses are structurally more conserved than the spike (S) proteins currently used in creating mRNA vaccines for a single variant of SARS-CoV-2, making the M proteins potentially more effective at protecting humans from a wide range of coronaviruses. It is hoped that this finding can serve as a starting point for the development of such a vaccine so that future pandemics caused by coronaviruses can be prevented.
Keywords: structural bioinformatics; COVID-19; SARS-CoV-2; MERS-CoV; SARS-CoV- 1; mRNA vaccine
INVESTIGATING AND PREDICTING THE FUTURE TRAJECTORY OF COVID-19 IN THE REGION OF WATERLOO
This paper is submitted as the course final project for AMATH 383: Introduction to Mathematical Biology at the University of Waterloo.
The COVID-19 pandemic has caused drastic chaos in the society and burdens on the global health systems in the past three years. Now with cases settling down and economy reopening, it is worth the effort to ask how the future trajectory of the disease looks like so preparations can be made beforehand. In this study, we developed an ODE based compartmental model as an attempt to investigate the future dynamic of COVID-19 in the Region of Waterloo. It was found that increasing vaccination rate can significantly help to delay and lower the major peaks of cases initially, while increasing vaccine effectiveness has no significant effect. As a result, it is hoped that public health agencies can focus on increasing vaccination coverage even with older vaccines that are less effective against the new variants so that future big resurgence of cases can be prevented.
Keywords: COVID-19; Mathematical model; Epidemiology; Vaccination
GOING BELOW AND BEYOND THE SURFACE: MICRONEEDLE STRUCTURE, MATERIALS, DRUGS, FABRICATION, AND APPLICATIONS FOR WOUND HEALING AND TISSUE REGENERATION
Microneedle, as a novel drug delivery system, has attracted widespread attention due to its non-invasiveness, painless and simple administration, controllable drug delivery, and diverse cargo loading capacity. Although microneedles are initially designed to penetrate stratum corneum of skin for transdermal drug delivery, they, recently, have been used to promote wound healing and regeneration of diverse tissues and organs and the results are promising. Despite there are reviews about microneedles, few of them focus on wound healing and tissue regeneration. Here, we review the recent advances of microneedles in this field. We first give an overview of microneedle system in terms of its potential cargos (e.g., small molecules, macromolecules, nucleic acids, nanoparticles, extracellular vesicle, cells), structural designs (e.g., multidrug structures, adhesive structures), material selection, and drug release mechanisms. Then we briefly summarize different microneedle fabrication methods, including their advantages and limitations. We finally summarize the recent progress of microneedle-assisted wound healing and tissue regeneration (e.g., skin, cardiac, bone, tendon, ocular, vascular, oral, hair, spinal cord, and uterine tissues). We expect that our article would serve as a guideline for readers to design their microneedle systems according to different applications, including material selection, drug selection, and structure design, for achieving better healing and regeneration efficacy.
DETERMINING NOVEL NATURAL RESERVOIRS AND STRAINS OF YERSINIA PESTIS THROUGH SRA DATABASE MINING
This paper is submitted as a part of my undergraduate thesis project at the University of Waterloo.
Yersinia pestis is a deadly bacterium that is responsible for multiple pandemics throughout history and still causes hundreds of deaths yearly in the less developed part of the world. To better monitor the evolution of this bacterium, a database search from the NCBI Sequence Read Archive (SRA) was conducted as an attempt to discover novel reservoirs and strains of Y. pestis. By using various bioinformatic tools to reconstruct the genome and phylogenetically classify the samples, it was found that Pseudogymnoascus destructans, commonly known as white-nose fungus from bats and is a previously undocumented reservoir for Y. pestis, carried four distinct strains of the bacterium, with one of them being a highly divergent and potentially novel strain from existing Y. pestis references. The results of this study illustrated the importance of genetic surveillance, and further investigations into the pathogenicity of those strains should be conducted in order to avoid future pandemics caused by Y. pestis.
Keywords: Genomic Surveillance; Sequence Read Archive; Yersinia pestis; Pseudogymnoascus destructans
APPLICATION OF HYDROGELS AS A DRUG DELIVERY SYSTEM FOR BONE REGENERATION
This paper is submitted as the course final research project for PHYS 380: Cellular and Molecular Biophysics at the University of Waterloo.
Treating bone diseases such as bone fracture and bone tumour has become a major topic in biomedicine due to increasing demand. However, it is often accompanied with high prices because of the complexity associated with the process. To tackle this issue, one of the biopolymer materials called hydrogels has attracted significant attention in the field of bone repair and regeneration. The physical properties of hydrogel, which include high adhesion, high biocompatibility, high functionality, and high volume of water content, enable hydrogels to promote the interaction of cells by mimicking the extracellular environment of human tissues and use itself as a vector for bone regeneration drugs. To help future researchers better utilize the potential of hydrogels, this review aims to provide a comprehensive guide for developing hydrogels to be used as a bone regeneration drug delivery system through the discussion of hydrogel materials, techniques for modifying hydrogels, and drugs that can be loaded onto hydrogels. It is hoped that with the help of an effective hydrogel, the above-mentioned problems with bone regeneration can be addressed in order to promote the development of biomedicine and benefit patients worldwide.
Keywords: Hydrogels, Bone Regeneration, Tissue Engineering, Drug Delivery
MATHEMATICAL MODELLING OF SARS-COV-2 IN-HOST VIRAL DYNAMICS AND ITS POTENTIAL ANTIVIRAL TREATMENTS
This paper is submitted as a part of the course final project for AMATH/BIOL 382: Computational Modelling in Cellular Systems at the University of Waterloo.
The COVID-19 pandemic caused by the SARS-CoV-2 virus presents an unprecedented challenge for the global health care system. As an effort to end this pandemic through the discovery of SARS-CoV-2 antiviral drug targets, the in-host dynamic of SARS-CoV-2 is simulated and analyzed using system biology and differential equation models. Once the validity of the models is confirmed, several potential target sites for the antiviral drugs are investigated and simulated by incorporating their interactions into the models. It is found that a hypothetical antiviral drug can effectively combat SARS-CoV-2 by activating the interferon production in the innate immune response, suggesting a potential path for COVID-19 drug development.
Keywords: mathematical modelling; SARS-CoV-2; systems biology; viral dynamics; antiviral drug
EVAPORATION-BASED, CO-AXIAL LOCK-AND-KEY FIBROUS RESERVOIR FOR LONG-TERM PREVENTION OF HYPERTROPHIC SCARS
Many diseases and conditions such as hypertrophic scarring require long-term maintenance over the healing cycle to achieve full recovery. However, there is a lack of wound dressings that can sustain over 90 days of therapeutic release. Inspired by the enhancement of wound healing by the nanofibrous morphology and diverse structures of electrospinning, we report an evaporation-based co-axial electrospun fibrous scaffold incorporating polymer brush gatekept nanocarriers for sustained delivery of therapeutics. The release rates of the system were demonstrated to be tunable through polymer graft length, while the system experienced minimal burst release when submerged under aqueous conditions. As a proof-of-concept, we target hypertrophic scarring by loading the system with doxorubicin, which led to inhibition of fibroblast activity without interfering with cell adhesion. Application of our scaffolds on rabbit ear hypertrophic scar models displayed that our scaffolds effectively reduced collagen density and scar-related gene expression in healing tissues, with improved tissue elevation outcomes. We envision that our long-term release scaffolds will be useful in combating long unresolved clinical dilemma such as tendon adhesion and tumor regression.
AN INVESTIGATION INTO THE PATHOGENICITY OF YERSINIA PESTIS
This paper is submitted as a part of the course project of BIOL 469: Genomics at the University of Waterloo.
With improved sanitation and the development of antibiotics to treat infections (Riedel, 2017), the plague has been viewed by many in developed nations as a problem of the past. Despite this, the modern plague remains a major public health issue in many less-developed parts of the world. The number of countries reporting incidences of this disease is increasing and the plague has been attributed to thousands of deaths within the previous decade (Stenseth et al., 2008; Keeling and Gilligan, 2000). Furthermore, there is also the possibility of a multi-drug resistant strain emerging and the consequential utilization of plague as a bioweapon for terrorism attacks (Tan et al., 2015). In response to these issues, the objective of this report is to determine the source of pathogenicity for the most recent modern plague-causing strain of Y. pestis CO92 (Orientalis) at the genetic level. This will be accomplished through the comparison of the genome for Y. pestis CO92 and other human pathogens (Y. pseudotuberculosis and Y. enterocolitica), as well as human non-pathogens (Yersinia kristensenii and Yersinia ruckeri) from the Yersinia genus. The results of this analysis can be used to understand the underlying mechanisms of Y. pestis pathogenicity so that more effective treatment methods and vaccines can be developed.
APPLICATION OF TPMS STRUCTURE IN BONE REGENERATION
Bone defect repair, due to its complex process in nature, has become a costly issue in modern day medicine. This causes a growing demand for a bone substitute that is effective and easy to construct. Recently, triply periodic minimal surface (TPMS) scaffolds, which embody trabecular bone-mimicking hyperboloidal topography, have become a promising candidate for this exact role due to their unique structure to promote many cellular processes. In response to the growing popularity of TPMS scaffolds amongst researchers, this review discusses the effect of different parameters (including pore size, porosity, and pore shape, as well as their influences on mechanical property, permeability, and curvature), along with the controlling and designing of such parameters, on bone regeneration to serve as a guide for future researchers in designing and utilizing TPMS scaffolds for bone regeneration purposes.
SITUATION REPORT REGARDING THE 2019 NOVEL CORONAVIRUS OUTBREAK
This report, initially written as a work term report in Winter 2020 for the employer, is selected as the exemplar report to be published in the course material for PD 11: Processes for Technical Report Writing at the University of Waterloo.
The purpose of this report is to provide the individuals at U-Link Business Solution with some key information regarding the current outbreak of the 2019 Novel Coronavirus Disease (COVID-19) in China. These pieces of information include but are not limited to the methods of spreading, the characteristics of the high-risk population, and the proactive measures that can be taken in order to prevent the spread of the virus within the company. The information included in this report is very important for employees to understand, because as the outbreak is happening in China, fear has grown within the company, which has greatly affected the employees’ productivity and mental health. Therefore, only through understanding the situation of the outbreak and the nature of the virus, people can regain confidence, restore their mental health, and be productive again.