Within-Host

Drug efficacy, resistance and toxicity

In cancer 

Drug resistance in cancer is a serious obstacle to recovery; resistance to BRAFi is just one example. New important examples are emerging, e.g., MEK inhibitor (S Kakadiaet al., Onco Targets Ther, 2018), NF-kB inhibitor (P Khongthong et al., Endocrine-Related Cancer, 2019), and PI3K-Akt inhibitor (J Wang et al., Mol Cancer, 2019). Combination therapy is often applied in order to reduce drug resistance in cancer. However, the lack of perfect synergy between the drugs (JS Lopez and U Banerji, Nat Rev Clin Onco, 2017) and the relatively accurate scheduling of the drugs (M Sturrock et al., Scientific Reports, 2018) remain significant challenges when fighting drug resistance. In some recent work, we have expressed drug resistance by putative functions that account for the drug-effective phase and the relapse phase of the treatment process. As a way forward to this study, I plan to investigate the intracellular protein network that lead cancer cell to develop resistance.

In viral disease 

The management of a chronic viral disease such as hepatitis B virus (HBV) infectio currently rests with long-term therapy using oral nucleoside analogues. The major limitation of long-term therapy is antiviral resistance, which is believed to be caused by the high rate of mutations that can occur during virus replication and the selection of these mutants due to a replication advantage in the presence of the antiviral agent. Our model on HBV, which accounted for the inflammatory and liver fibrosis pathways, and which was used to study how two drugs could be given synergistically despite their respective side effects, could be extended to propose better treatment for the antiviral resistance that occurs during long-term therapy of chronic HBV in particular, and viral diseases in general.

In bacterial disease 

Antibiotic resistance is the ability of bacteria or other microbes to resist the effects of an antibiotic. Antibiotic resistance occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs, chemicals, or other agents designed to cure or prevent infections (E Peterson and P Kaur, Front Microbiol, 2018; N Yamamoto et al., Antimicrobial Resistance and Infection Control, 2019; B Aslam et al., Infect Drug Resist, 2018). A common approach to treat the resistance is to combine the current drug with one or many other drugs such that the overall effects inhibit bacteria replication. How much and in what schedule to administer the drug play and important factor. We aim to understand the known mechanisms of resistance, and then use a mathematical model to address the question of optimal protocol of treatment. I would also like to explore the fascinating question whether there are some connections between the mechanisms of drug resistance in bacteria and drug resistance in cancer.