Luca Lignitto

NYU Langone Medical Center, New York

Deciphering the heme code in physiology and disease

My work focuses on the role of heme signaling in mammalian physiology and pathology with a particular interest in the regulation of heme-sensor proteins. Heme is an essential and ubiquitous metallonutrient that functions as a prosthetic group for a plethora of enzymes. In addition to its role as a cofactor, unbound heme is a versatile signaling molecule that dynamically regulates a number of pathways, ranging from mitochondrial respiration to metabolism and circadian rhythms, by reversibly binding to and modulating the activity of the heme-sensor proteins.

Recently, I uncovered a molecular network that links lung cancer-associated genetic mutations of the Ubiquitin-Proteasome System to perturbation of the heme signal, which ultimately promotes tumor dissemination. My research aims to use a broad spectrum of experimental systems and levels of resolution – atomic, molecular and organismal – to define the molecular machineries modulating the transmission of the heme signal and to discover how deregulation of this pathway contributes to disease mechanisms.

Selected publications

• Lignitto et al. (2019) Nrf2 activation promotes lung cancer metastasis by inhibiting the degradation of Bach1. Cell 178(2):316-329
• Lignitto et al. (2013) Proteolysis of MOB1 by the ubiquitin ligase praja2 attenuates Hippo signalling and supports glioblastoma growth. Nat Commun 4:1822
• Lignitto et al. (2011) Control of PKA stability and signalling by the RING ligase praja2. Nat Cell Biol 13(4):412-22

Contact: Isabelle Saves (Isabelle.Saves@ipbs.fr)

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