REMINDER: Department of Infection, Immunity & Cardiovascular Disease Seminar – Tuesday 22nd May 2018

Title:  “Understanding and subverting leukocytic responses to sterile injury”
Speaker:  Dr Aleksandar Ivetic, King’s College London.
Venue:  Lecture Theatre 3, F Floor, Medical School.
Time:  12:30pm – 1:30pm
Abstract:  Inflammatory cells, such as monocytes and neutrophils are absolutely essential for keeping infections at bay. Intriguingly, the same immune cells can exacerbate “sterile (non-infectious) injury” in cardiovascular disease (e.g. atherosclerosis and myocardial infarction (MI)). Unearthing the molecular basis underpinning these conflicting leukocytic behaviours could provide a way in which to expose novel therapeutic targets that reduce sterile injury, but retain aggressive targeting of pathogens.

Alex is interested in understanding the cellular and molecular biology underpinning the inflammatory response, with a major focus on leukocytes and endothelial cells. Much of Alex’s research uses state-of-the-art microscopy; therefore taking a “seeing is believing” approach to his work. A recent sabbatical at the University of Calgary in the laboratory of Prof. Paul Kubes has enabled him to undertake in vivo imaging to model acute inflammatory responses.

For enquiries, please contact: iicd@sheffield.ac.uk


FUTURE EVENTS FOR THE DIARY:

Monday 11th June 2018
Title: “Respiratory Viral Infections at the Extremes of Age”
Speaker:  Dr Fiona Culley, Imperial College London.
Venue:  Lecture Theatre 3, F Floor Medical School.
Time:  12:30pm – 1:30pm
Abstract:  Respiratory Syncytial Virus (RSV) infection causes colds in most healthy adults, but in the very young and the elderly it can cause severe disease. Severe RSV infection in the very young (bronchiolitis) is associated with long term wheeze and asthma in childhood. Our work aims understand what is different about the immune system in the lung of the very young that makes infants more susceptible to infection. More recently our work on infection in elderly has allowed us to explore age dependent susceptibility to infectious disease.


Thursday 28th June 2018
Title: 
“Senescence: connecting cancer and inflammation”
Speaker:  Professor Jesus Gil, Imperial College London.
Venue:  Lecture Theatre 3, F Floor Medical School.
Time:  12:30pm – 1:30pm
Abstract:  Oncogene-induced senescence is a potent tumor-suppressive response. Paradoxically, senescence also induces an inflammatory secretome that promotes carcinogenesis and age-related pathologies. Consequently, this “senescence-associated secretory phenotype” (SASP) is a potential therapeutic target. We performed an RNAi screen for genes that regulate the SASP without affecting the senescence growth arrest. We identified 50 druggable targets whose knockdown suppresses the inflammatory secretome and differentially affects other SASP components. Amongst the screen candidates was PTBP1, a factor regulating alternative splicing. Knockdown of PTBP1 prevents the pro-tumorigenic effects of the SASP without interfering with growth arrest. PTBP1 regulates the alternative splicing of genes controlling intracellular trafficking, such as the exocyst component EXOC7. We found that PTBP1-mediated EXOC7 isoform switching modulates exocyst activation to regulate the SASP. Our study identifies PTBP1 and EXOC7 as new regulators of inflammation and provides functional evidence that specific regulation of the SASP represents a powerful therapy against inflammation driven cancer.