De Santo was awarded a research fellowship in the experimental physics division of CERN. She joined the University of Oxford, working with Alfons Weber, as a postdoctoral research fellow in 2000.[2][4] At Oxford, De Santo studied neutrino physics.[5] In 2003 De Santo joined Royal Holloway, University of London as a lecturer.[2] She was coordinator for the ATLAS experiment-UK supersymmetry group and led the working group looking for three leptons in the excited state.[6][7]
She was appointed an associate professor at the University of Sussex in 2009.[2] She founded the Sussex team working on the Large Hadron Collider.[2] She is searching for evidence of supersymmetry in proton-proton interactions.[8] She is interested in luminosity upgrades at the ATLAS experiment.[9]
In 2013 she became the University of Sussex's first woman professor in the department of physics.[10] She was the Head of Experimental Particle Physics at the University of Sussex between 2011 and 2017. She was awarded a Science and Technology Facilities Council consolidator grant in 2012 and 2015 that allowed her to work on the ATLAS experiment.[8] She teaches the advanced particle physics course.[11] In 2016 she arranged the annual meeting of the Institute of Physics High Energy Particle Physics group at the University of Sussex.[12]
In 2017 she was awarded a Royal Society Wolfson Research Merit Award allowing her to search for physics beyond the Standard Model.[2][13] She was a member of the ATLAS experiment Speakers Committee and of the ATLAS Publication Committee.[2]
De Santo launched the annual University of Sussex particle physics masterclasses for school students.[2][14] She has presented her work at several Royal Society Summer Exhibitions. The Sussex SUSY Softies, a series of knitted particles that explained the main features of neutralinos, were one of the most popular aspects of the 2014 exhibition.[15] Between 2017 and 2020, she was a governor of Cardinal Newman Catholic School, Hove.[16] She collaborated with the artists Joe Gerhardt and Ruth Jarman to create a work of art, HALO, that incorporated the results of CERN's particle collisions.[17] It was commissioned by Audemars Piguet for Art Basel.[17]
