The first seminar in the series focused on the pathogenesis of skin neglected tropical diseases (NTDs), featuring expert insights into two major challenges: cutaneous leishmaniasis and Buruli ulcer. It was the first of two seminars dedicated to Skin NTD pathogenesis.
Immunopathogenesis in Cutaneous Leishmaniasis
Dr Fernanda Oliveira Novais, The Ohio State University, USA
Cutaneous leishmaniasis presents with a wide range of clinical outcomes, with immune responses often driving much of the pathology. Dr Novais discussed her laboratory’s investigations into the immune mechanisms that promote tissue damage without contributing to parasite control, and how this knowledge could help identify novel immunotherapeutic strategies.
Inhibition of Sec61 by Mycolactone – A Virulence Mechanism with Major Impacts on Cellular Physiology Spanning Immunology, Cytotoxicity and Cardiovascular Function
Prof Rachel Simmonds, University of Surrey, UK
It has been more than a decade since mycolactone was first shown to inhibit protein translocation into the endoplasmic reticulum via the Sec61 translocon. Since then, significant advances have been made in understanding how this interaction triggers a cascade of effects, ultimately leading to the necrotic skin ulcers characteristic of Buruli ulcer. In this talk, Prof Simmonds explored the broader implications of these findings for our understanding of Mycobacterium ulcerans biology and argued that prevention through vaccination is preferable to current treatment options.
About the Speakers
Dr Fernanda Oliveira Novais, The Ohio State University, USA
Dr Novais is an Assistant Professor at The Ohio State University and Co-Director of the Host Defense and Microbial Biology Program at the Infectious Diseases Institute. With more than 20 years of experience in immunology, her research combines murine models and human studies to investigate immune pathways associated with severe disease and treatment failure in cutaneous leishmaniasis.
Prof Rachel Simmonds, University of Surrey, UK
Prof Simmonds’ research group focuses on the mechanism of action of mycolactone, the lipid-like immunosuppressive toxin associated with Buruli ulcer. Mycolactone has many unusual biological activities, and in 2014 her group identified its mechanism of action as an inhibitor of Sec61-dependent protein translocation.
The group is now applying this knowledge to improve understanding of Buruli ulcer and fundamental cell biology. Its findings have also revealed an important role for haemostasis in Buruli ulcer, including its possible relationship with susceptibility to infection. Together, Prof Simmonds’ research supports efforts to improve the prevention, transmission control, diagnosis and treatment of this neglected tropical disease.
