Titia de Lange's research interest centers on telomeres and their role in human disease. She described the shelterin complex and showed how it hides the telomere end from the DNA damage response, in part by forming the t-loop structure. Her laboratory also studies the dual role of telomeres in cancer, including tumor suppression by telomere shortening and the induction of genome instability by telomere dysfunction in later stages of tumorigenesis.

As an undergraduate at the University of Amsterdam, de Lange worked with Richard Flavell (FRS) at the NIMR in Mill Hill. She conducted her thesis research at the University of Amsterdam with Piet Borst (ForMemRS), receiving her PhD in 1984. After postdoctoral research with Harold Varmus (ForMemRS) at UCSF, she joined the faculty of Rockefeller University in 1991, where is the Leon Hess Professor and Director of the Anderson Center for Cancer Research.

De Lange is a member of the US National Academies of Sciences and Medicine, the Dutch Royal Societies (KNAW and KHMW), and EMBO.  Her awards include the Gairdner International Award, the Breakthrough Prize in Life Sciences, the Heineken Prize, and the Rosenstiel Award.