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Dr. Thilona Arumugam

RESEARCH PROJECT:  Decoding the role of DNA methylation in HIV pathogenesis

    Four medical science degrees, a postdoctoral research fellowship and a dedication to science that was nurtured at primary school, have Dr Arumagam focusing on eradicating HIV infection, using CRISPR-based techniques to control the regulation of host genes associated with HIV pathogenesis.


    Currently a postdoctoral research fellow at the University of KwaZulu-Natal, explains the importance of this research: “HIV is one of the world’s most fatal diseases. It is caused by a virus that attacks the body’s immune system preventing the body from fighting against the virus. There is no cure for HIV/AIDs, however, treatment {Antiretroviral treatment, ART) does exist.  ART works by preventing the virus from making more copies of itself but sometimes the virus hides in a dormant state in certain areas where ART cannot reach therefore a cure cannot fully be achieved. The virus is not the only factor contributing to HIV disease outcomes. Host (human) factors are also important determinants of how a person responds to the virus. Certain human genes influence how we fight HIV. By controlling the regulation of certain human genes associated with HIV disease, an alternative form of HIV therapy can be achieved.”  


    She goes on to explain that a gene is a short sequence of DNA that contains instructions that tell your cells to make functional molecules called proteins. Certain genes/proteins help us fight against HIV, while others help HIV infect us. One method of controlling these genes is by manipulating the methylation (a chemical modification that can prevent genes from being expressed and being made into proteins) status of these genes using a technique called CRISPR to decrease the expression of these genes.


    Over the last two decades, she says, ART has dramatically improved the management of HIV infection remarkably declining the morbidity and mortality associated with HIV/AIDS. “However, ART does have its limitations, she adds. “It is impossible for ARTs to fully eliminate HIV from infected individuals, lifelong adherence is required to suppress HIV which can lead to the development of severe side effects or the development of drug resistance when treatment is not taken correctly. Therefore, novel treatment strategies that completely eliminate the virus and are independent of lifelong adherence are essential.”


    Dr Arumugam believes that CRISPR-based manipulation of the DNA methylation status of certain HIV-associated host genes can effectively control HIV replication which could be used to prevent and treat HIV infections. This technique may be safer due to its reversibility and will provide alternative approaches to HIV therapy, that do not require lifelong dependency on ARV.


    Although she is an eleven-time author and a multiple award-winner in her field, Dr Arumugam generously shares the path of self-doubt that she sometimes walked. 

    “I think there comes a time in almost every scientist’s career-  especially female scientists -when imposter syndrome sets in and you become discouraged. An important lesson that I learnt was that I’m not alone, and that feeling is almost universal.”

    Her advice to others facing the same barrier is to work on something that excites you and to follow your curiosity, in order to remain positive. Support from peers and family is also important, she says. “But most importantly remind yourself of your strengths as it will help you when you have moments of self-doubt.”


    Epigenetics is where her passion lies and she looks forward to contributing to this field. She aspires to run her own research laboratory that has specific focus on African populations, who are debilitatingly underserved when it comes to genome sequencing, given its gene diversity and high propensity to adverse drug-related toxicities.


    She is quick to give credit to early influencers on her science journey: firstly, the Eskom Expo for Young Scientists which saw her winning multiple awards at all levels for six years. “Participating at Expo was a life-changing experience,” she says. She also credits the support she got from her family especially her mother, Imantha – who supported her when she faced obstacles and disappointments. 


    She encourages young girls with curious minds and a thirst for knowledge, to consider a career in science: “Follow your passion, turn your dreams into a reality and don’t let anyone including yourself hold you back. Yes, you will feel overwhelmed at times but when you do take a step back, breath and I promise you will be back with more drive than ever before.  Be bold, be confident, and take that leap into science. Just do it!”

    Research Summary

    UNAIDS aims to eradicate the AIDS epidemic by the year 2030. 

    Despite recent advances in anti-HIV therapy, HIV infection continues to spread worldwide, most notably in sub-Saharan Africa with about 5,500 new infections every day. Although current HIV regimens function by suppressing viral replication, HIV is still able to persist in a latent form within the body. 

    Controlling the expression of human host genes that HIV relies on may be more effective in completely eradicating HIV from the body. Methylation of specific regions within the genome can influence gene expression, and aberrant distribution of DNA methylation is associated with a spectrum of human diseases including HIV. Identifying human host genes that are differentially methylated during HIV infection and developing tools that will be able to manipulate the methylation status of the identified genes may provide a new strategy for therapeutic application against HIV-1 infection. 

    This study aims to understand the influence of DNA methylation on host genes regulating HIV pathogenesis by assessing the differential DNA methylation regulation of host genes across different stages of HIV infection (pre-, acute, chronic HIV infection and post-ART) using a genome-wide approach.

     The study further aims to use CRISPR-based manipulation of the DNA methylation status of identified HIV-associated host genes to effectively control HIV replication in vitro.

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