Lara Manganaro - Researcher
Department and institution: Istituto Nazionale di Genetica Molecolare “Romeo ed Enrica Invernizzi” INGM
email: manganaro@ingm.org
tel. +39 02 00660303
Curriculum Vitae
see also: Google Scholar, ORCID
Keywords: HIV, latency, CD4 T cells
Research interests
HIV persists over decades despite seemingly effective antiretroviral treatment (HAART). HIV persistence relates to the fact that HIV integrates into the genome of the host cell, thus becoming an integral part of cellular DNA. Infected cells harboring a transcriptionally silent “latent” provirus evade immune surveillance and persist over many years despite long-term HAART. While there is agreement that memory CD4 T cells play a central role in HIV persistence, fundamental gaps remain in our understanding of how HIV latency is established and maintained.
Emerging evidence suggest that CD4 T memory stem cells (TSCM), the least differentiated of all CD4 T cell memory populations, support HIV infection. However, the extent of the impact of TSCM on establishment of HIV latency, persistence and the underlying molecular mechanisms remain unknown. We hypothesize that HIV exploits the stemness of TSCM to create a persistent, self-renewing HIV reservoir, which bypasses the need for de novo infection. Understanding the molecular mechanisms underlying HIV persistence in CD4+ T memory stem cells is essential to develop targeted interventions allowing shrinking and purging of the latent reservoir.
Main topics of the group
HIV infection, latency establishment, innate immunity
Current research projects
Ministero della Salute, Ricerca Finalizzata-Giovani Ricercatori
“CD4 T memory stem cells in the context of HIV infection"
In collaboration with Dr. Andrea Gori, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Milano
Internal and external collaborators
Dr. Andrea Gori, Unità Operativa Complessa Malattie Infettive, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Milano
Dr. Viviana Simon, Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA
Selected Publications
IL-15 regulates susceptibility of CD4+ T cells to HIV infection
Manganaro L, Hong P, Hernandez MM, Argyle D, Mulder LCF, Potla U, Diaz-Griffero F, Lee B, Fernandez-Sesma A, Simon V.
Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):E9659-E9667. doi: 10.1073/pnas.1806695115.
Tumor suppressor cylindromatosis (CYLD) controls HIV transcription in an NF-κB-dependent manner.
Manganaro L, Pache L, Herrmann T, Marlett J, Hwang Y, Murry J, Miorin L, Ting AT, König R, García-Sastre A, Bushman FD, Chanda SK, Young JA, Fernandez-Sesma A, Simon V.
J Virol. 2014 Jul;88(13):7528-40. doi: 10.1128/JVI.00239-14.
Concerted action of cellular JNK and Pin1 restricts HIV-1 genome integration to activated CD4+ T lymphocytes.
Manganaro L, Lusic M, Gutierrez MI, Cereseto A, Del Sal G, Giacca M.
Nat Med. 2010 Mar;16(3):329-33. doi: 10.1038/nm.2102.
last update: July 2019