Profile
Paula Longhi graduated from Buenos Aires University (UBA) with a degree in Biochemistry in 2001. In 2006 she obtained her PhD at Cardiff University, under the mentoring of Dr Awen Gallimore and Prof Paul Morgan. During her PhD she studied the role of complement in the induction of innate and adaptive immunity to tumors and virus infection. With the intention to gain a deeper and broader understanding of immune responses, in 2006 Dr Longhi joined the Laboratory of Ralph Steinman where she worked in the design of dendritic cell-based vaccines to prevent many illnesses such as HIV, malaria, leishmania and cancer. During this time, she expanded her knowledge on dendritic cell biology and focused her research in the cellular processes associated with DCs maturation. Dr Longhi joined the William Harvey Research Institute in 2013 with the aim of manipulating DC maturation to control unwanted reactions (e.g. atherosclerosis) and to promote desired immune responses (e.g. protective vaccines).
Research
Dr Longhi research focuses on understanding the intricate differentiation process of dendritic cell maturation (DCs) and how can ultimately influence the outcome of the adaptive T cell response. DCs are the main antigen presenting cells for initiating primary immune responses. DCs patrol the bloodstream and tissues to sense danger signals as bacteria, viruses or toxins. After exposure to such stimuli they undergo an extensive maturation process, which results in the expression of co-stimulatory molecules, cytokine production and enhanced migration to draining lymph nodes (LNs), where they present antigens to naive T cells.
Appropriate activation and maturation of DCs, is needed to induce adaptive T cell immunity. However, the definition of “mature” DCs has major gaps at the molecular and biological levels. Up to now, maturation has focused on up-regulation of surface MHC-II and costimulatory molecules and production of pro-inflammatory cytokines. These assays for “phenotypic” maturation do not fully capture the biology of “functional” DC maturation, which leads to T cell immunity. It is, therefore important to define the molecular changes and functional switches required for the generation of functionally mature DCs.
Dr Longhi is currently working on two main projects:
- Identification of novel pathways for DC maturation and their influence on adaptive T cell responses.
- Study the role of metabolic reprogramming during DC maturation in the development of vascular inflammation and atherosclerosis.
