Longhi, Paula

Paula Longhi

Early Career Researcher

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 WHRI 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).

Summary of 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:

  1. Identification of novel pathways for DC maturation and their influence on adaptive T cell responses.

  2. Study the role of metabolic reprogramming during DC maturation in the development of vascular inflammation and atherosclerosis.
 

Key Publications

For a full list of publist publications click here

Pantel A, Teixeira A, Haddad E, Wood EG, Steinman RM, Longhi MP (2014). Direct Type I IFN but Not MDA5/TLR3 Activation of Dendritic Cells Is Required for Maturation and Metabolic Shift to Glycolysis after Poly IC Stimulation. PLoS Biol. Jan;12(1):e1001759. 

Barbuto S, Idoyaga J, Vila-Perelló M, Longhi MP, Breton G, Steinman RM, Muir TW (2013).Induction of innate and adaptive immunity by delivery of poly dA:dT to dendritic cells. Nat Chem Biol. Apr;9(4):250-6.

Trumpfheller C, Longhi MP; Caskey M, Idoyaga J, Bozzacco L, Keler T, Schlesinger S, Steinman RM. Dendritic cell-targeted protein vaccines: a novel approach to induce T cell immunity. J Intern Med. (2012); Feb;271(2):183-92 

Pantel A, Teixeira A, Haddad E, Wood EG, Steinman RM, Longhi MP (2014). Direct Type I IFN but Not MDA5/TLR3 Activation of Dendritic Cells Is Required for Maturation and Metabolic Shift to Glycolysis after Poly IC Stimulation. PLoS Biol. Jan;12(1):e1001759. 

Barbuto S, Idoyaga J, Vila-Perelló M, Longhi MP, Breton G, Steinman RM, Muir TW (2013).Induction of innate and adaptive immunity by delivery of poly dA:dT to dendritic cells. Nat Chem Biol. Apr;9(4):250-6.

Pantel A, Cheong C, Dandamudi D, Shrestha E, Mehandru S, Bozzacco L, Steinman RM, Longhi MP. A new synthetic TLR4 agonist, GLA, allows antigen targeted dendritic cells to elicit Th1 immunity in vivo. Eur J Immunol.(2012) Jan;42(1):101-9.

Bozzacco L, Trumpfheller C, Huang Y, Longhi MP, Shimeliovich I, Schauer JD, Park CG, Steinman RM. HIV gag protein is efficiently cross-presented when targeted with an antibody towards the DEC-205 receptor in Flt3 ligand-mobilized murine DC. Eur J Immunol.(2010) Jan;40(1):36-46.

Longhi MP, Trumpfheller C, Idoyaga J, Caskey M, Matos I, Kluger C, Salazar AM, Colonna M, Steinman RM. Dendritic cells require systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J. Exp. Med.(2009) 206(7):1589-602

Trumpfheller C, Caskey M, Nchinda G, Longhi MP, Mizenina O, Huang Y, Schlesinger SJ, Colonna M, Steinman RM. The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. PNAS (2008).19;105(7):2574-9

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