Rate My Professor Michael Lieber

The Lieber lab examines physiologic and pathologic gene rearrangements involving DNA double-strand breaks in the immune system, cancer, and aging. Central to this is V(D)J recombination, which generates diversity in B- and T-lymphocyte receptors; defects in enzymes like RAG proteins cause severe combined immunodeficiency (SCID). The lab elucidates the nonhomologous DNA end joining (NHEJ) repair pathway, the primary mechanism in mammalian cells for resolving such breaks from radiation or oxidative damage. Key proteins include Ku, which binds broken ends; the Artemis:DNA-PKcs complex, whose nuclease activity is activated by DNA-PKcs phosphorylation for end trimming; polymerases μ and λ, which fill gaps and add nucleotides templatelessly akin to TdT; and the DNA ligase IV/XRCC4/XLF complex for final ligation. Research addresses chromatin modulation of these processes, NHEJ imprecision fostering somatic mutations in aging and cancer, and inhibitors to boost cancer therapy or stem cell gene targeting. Additional foci encompass V(D)J errors yielding chromosomal translocations in 40% of non-Hodgkin lymphomas due to fragile sites near oncogenes, and class switch recombination where AID deaminates cytidines on R-loop single-stranded DNA from transcription. Lieber has produced landmark publications such as "The molecular basis and disease relevance of non-homologous DNA end joining" (2020), "Pol X DNA polymerases contribute to NHEJ flexibility" (2023), and "The mechanisms of human lymphoid chromosomal translocations and their medical relevance" (2022). His work garners sustained NIH funding, including R35GM118009 through 2026 and R01 grants since 1990, profoundly shaping DNA repair, immunology, oncology, and gerontology.