Thavy Long

Degrees

BSc, MSc, University of Lille 1 - France
PhD, University of Lille 2 - France

Short Bio

Dr. Thavy Long obtained her MSc thesis in Genetic and Microbiology and PhD in Cell Biology from University of Lille (France). It was during her PhD with Dr Colette Dissous that she really developed an interest in the molecular and cellular biology of helminths and particularly of Schistosoma mansoni, a parasitic flatworm of humans. Her past project involved studies on protein kinases that regulate the development of reproductive organs and egg production in S. mansoni. She has also led numerous drug discovery and development projects against schistosomes during her postdoc-trainings with Dr. Conor Caffrey and Dr. James McKerrow at UC San Francisco and UC San Diego. Recently, she gained expertise on the biology of filarial parasites including the heartworm Dirofilaria immitis that infects companion animals by investigating the signaling pathways that govern the development of the infective stage. As an Assistant Professor at the Institute of Parasitology, Dr Long is interested in understanding the molecular mechanisms involved in immune evasion, developmental processes and metabolism of helminths including trematodes and filarial nematodes, to identify novel targets that could be the basis for new anthelminthics. In addition, her research focuses on developing tools to monitor the spread of drug resistance and elucidating the mechanisms of drug resistance in helminth parasites.

Awards and Recognitions

Prestige Marie Curie Fellowship - Postdoctoral Fellowship

Research Interests

Professor Long's research focuses on the molecular basis underlying the intracellular communication in schistosomes as well as the dialogue between schistosomes and their host. In her laboratory, they aim to identify schistosome molecular actors that are involved in this process as well as their associated receptors in the parasite and/or the host which could be the basis for the development of novel therapies against schistosomiasis.

Current Research

Helminths are parasitic worms of medical and veterinary importance. They infect billions of individuals worldwide and are responsible for chronic diseases in livestock and companion animals leading to significant economic losses. Treatment and control of helminthiasis are limited and mostly rely on a few anthelminthics (AHs) for which mass drug administration has already led to drug resistance in nematodes, and threats to extend to trematodes. No recombinant vaccines are available. Alternative treatment strategies are urgently needed. In this context, understanding the worm biology and the strategies employed by those parasites to thrive in hostile environment or under drug pressure is crucial to the identification of novel gene/protein targets for drug or vaccine development. Moreover, epidemiological studies around the world reported an inverse relationship between the prevalence of inflammatory diseases (ID) and helminth infections, leading to the “hygiene hypothesis” and suggesting the potential protection of helminths against ID, via host immune system regulation.

Schistosomes can establish long-term chronic infections as they can survive for up to 40 years in their human host. Clearly, these parasites have evolved to evade or manipulate the host immune system by creating an immunoregulatory environment. The mechanisms by which schistosomes interact with its mammalian host and alter the host immune response remain unknown. Like all helminths, schistosomes release excretory-secretory products (ESPs) which are at the heart of molecular dialogues in host-parasite interactions (HPI). Helminth extracellular vesicles (EVs) are components of ESPs and recently emerge as key players in cell-to-cell communication and in regulating the immune response. However, their specific role in the infection process and pathology of S. mansoni is not well understood.

Another interesting aspect of helminths is their reliance on the host cholesterol and sterol derivatives as helminths are incapable of synthesizing sterols de novo which emphasizes how intricate is the parasite-host interplay. How helminths acquire sterols and whether they metabolize them are unknown. Derivatives of cholesterol such as steroid hormones or bile acids exercise their function via the binding to nuclear receptors (NRs) that work in concert with other proteins to regulate the expression of specific genes controlling development, homeostasis, reproduction and metabolism. In schistosomes, steroid hormones have been shown to impact their physiology and NRs have been structurally characterized but their function are still unknown, and no apparent hormone-receptor complex has been described so far.

Resistance to current anthelminthics such as macrocyclic lactones (ML) is a significant problem worldwide threatening the health of individuals and animals. The mechanisms of resistance to ML are not completely understood. Moreover, monitoring the spread of drug resistance is challenging in absence of adequate tools. Understanding how helminths survive to drug pressure could lead to new treatment options that could also potentiate current AHs.

Dr Long’s laboratory is interested in:

• Identifying the schistosome- and heartworm-derived molecules with immunomodulation and therapeutic potential
• Deciphering the genetic and molecular basis by which steroid hormones affect the development in trematodes and filarial parasites
• Investigating the role of steroid hormones in the phenotypic plasticity of S. mansoni and particularly in the adaptation to a parasitic lifestyle
• Unravelling the mechanisms developed by the parasite to exploit cholesterol from the host
• Unravelling strategies employed by the parasite to survive to drug pressure
• Developing novel tools to understand and monitor drug resistance in helminths

Courses

Publications

View a list of current publications on Google Scholar