Peter Ly, Ph.D. Assistant Professor School Medical School Department Pathology | Cell Biology Graduate Programs Cancer Biology, Genetics, Development and Disease Biography The Ly Laboratory studies the causes and consequences of genomic instability in the context of cancer development. Cancer cells frequently harbor complex genomes that are characterized by numerical and structural chromosomal abnormalities. Our laboratory is currently investigating the cellular and molecular mechanisms that shape the chaotic mutational landscape of cancer genomes. We are particularly interested in a class of complex genome rearrangements generated by the catastrophic shattering of individual chromosomes. This process – termed chromothripsis – is initiated by mitotic cell division errors in which mis-segregated chromosomes become spatially entrapped within aberrant nuclear structures called micronuclei. DNA damage and DNA replication defects within micronuclei trigger the shattering of the mis-segregated chromosome into tens to hundreds of genomic fragments. Attempts by error-prone DNA repair pathways to reassemble the shattered fragments result in the formation of highly rearranged chromosomes with extensive DNA copy-number alterations. Chromothripsis exemplifies a rapid mutational process in which numerous genetic lesions can be acquired within a few cell cycles, ranging from the simultaneous inactivation of multiple tumor suppressor genes to the production of extrachromosomal DNA with amplified oncogenes. Our long-term goal is to understand how mitotic errors, micronuclei, and chromothripsis contribute to cancer genome instability, tumorigenesis, and resistance to anti-cancer therapeutics. Our research program employs a number of interdisciplinary approaches bridging molecular cell biology and genetics, including CRISPR/Cas9 screens, high-resolution fixed- and live-cell microscopy, cytogenetics, and genomics. We also strive to create a supportive, diverse, and inclusive laboratory environment aimed at offering exceptional training and career development opportunities for fellows and students. Peter Ly received his B.A. in Biology from Baylor University and Ph.D. in Cancer Biology from UT Southwestern Medical Center. During graduate training with Jerry Shay and Woodring Wright, he studied how aneuploidy – an abnormal number of chromosomes – promotes malignant transformation. He conducted postdoctoral training at the University of California San Diego and Ludwig Institute for Cancer Research with Don Cleveland, where he developed chromosome-specific mis-segregation approaches to reconstruct the mechanisms leading to complex structural genomic rearrangements in human somatic cells. In 2019, Dr. Ly joined the faculty of UT Southwestern Medical Center as an Assistant Professor in the Department of Pathology and CPRIT Scholar in Cancer Research. He holds a secondary appointment in the Department of Cell Biology and is a member of the Harold C. Simmons Comprehensive Cancer Center as part of the Cellular Networks in Cancer Program. He has been an active member of the American Society for Cell Biology since 2013. Undergraduate Baylor University (2008), Biology Graduate School University of Texas Southwestern Medical Center (2012), Cancer Biology Postdoctoral Fellowship University of California San Diego, Ludwig Institute for Cancer Research (2019), Cell Biology Research Interest Cell cycle and cell division Chromosome rearrangements DNA damage response and repair Genomic instability in cancer Mechanisms of chromothripsis Publications Featured Publications The Fanconi anemia pathway induces chromothripsis and ecDNA-driven cancer drug resistance. Engel JL, Zhang X, Wu M, Wang Y, Espejo Valle-Inclán J, Hu Q, Woldehawariat KS, Sanders MA, Smogorzewska A, Chen J, Cortés-Ciriano I, Lo RS, Ly P, Cell 2024 Aug Non-homologous end joining shapes the genomic rearrangement landscape of chromothripsis from mitotic errors. Hu Q, Espejo Valle-Inclán J, Dahiya R, Guyer A, Mazzagatti A, Maurais EG, Engel JL, Lu H, Davis AJ, Cortés-Ciriano I, Ly P, Nat Commun 2024 Jul 15 1 5611 Induction of chromosome-specific micronuclei and chromothripsis by centromere inactivation Lin YF, Hu Q, Guyer A, Fachinetti D, Ly P Methods Cell Biol. 2024 Boveri and beyond: Chromothripsis and genomic instability from mitotic errors. Mazzagatti A, Engel JL, Ly P, Mol Cell 2023 Nov Mitotic clustering of pulverized chromosomes from micronuclei. Lin YF, Hu Q, Mazzagatti A, Valle-Inclán JE, Maurais EG, Dahiya R, Guyer A, Sanders JT, Engel JL, Nguyen G, Bronder D, Bakhoum SF, Cortés-Ciriano I, Ly P, Nature 2023 May Mechanistic origins of diverse genome rearrangements in cancer. Dahiya R, Hu Q, Ly P, Semin Cell Dev Biol 2021 Apr Chromothripsis drives the evolution of gene amplification in cancer. Shoshani O, Brunner SF, Yaeger R, Ly P, Nechemia-Arbely Y, Kim DH, Fang R, Castillon GA, Yu M, Li JSZ, Sun Y, Ellisman MH, Ren B, Campbell PJ, Cleveland DW, Nature 2020 Dec Chromosome segregation errors generate a diverse spectrum of simple and complex genomic rearrangements. Ly P, Brunner SF, Shoshani O, Kim DH, Lan W, Pyntikova T, Flanagan AM, Behjati S, Page DC, Campbell PJ, Cleveland DW Nat. Genet. 2019 Mar Chromosomal instability drives metastasis through a cytosolic DNA response. Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, Shah P, Sriram RK, Watkins TBK, Taunk NK, Duran M, Pauli C, Shaw C, Chadalavada K, Rajasekhar VK, Genovese G, Venkatesan S, Birkbak NJ, McGranahan N, Lundquist M, LaPlant Q, Healey JH, Elemento O, Chung CH, Lee NY, Imielenski M, Nanjangud G, Pe'er D, Cleveland DW, Powell SN, Lammerding J, Swanton C, Cantley LC Nature 2018 Jan 553 7689 467-472 Rebuilding Chromosomes After Catastrophe: Emerging Mechanisms of Chromothripsis. Ly P, Cleveland DW Trends Cell Biol. 2017 12 27 12 917-930 Results 1-10 of 35 1 2 3 4 Next Last Honors & Awards American Cancer Society - Institutional Research Grant Award (2022) Early-Career Investigator, DoD Academy of Kidney Cancer Investigators (2022) UT Southwestern Haberecht Wildhare-Idea Research Award (2022) UT Southwestern Circle of Friends Research Award (2020) CPRIT Scholar in Cancer Research, Cancer Prevention & Research Institute of Texas (2019) Forbeck Scholar, William Guy Forbeck Research Foundation (2019) James Kerr Award for Research Excellence, Ludwig Institute for Cancer Research (2017) NIH/NCI Pathway to Independence Award (K99/R00) (2017) Hope Funds for Cancer Research Fellow (2014) NIH/NCI Cancer Cell Biology Postdoctoral Training Grant Award (2013) CPRIT Predoctoral Training Grant Award, Cancer Prevention & Research Institute of Texas (2010) Jack G. and Norma Jean Folmar Research Scholarship, Baylor University (2007) Rubin and Sarah Shaps Scholar, Memorial Sloan-Kettering Cancer Center (2007) Professional Associations/Affiliations American Society for Cell Biology (2013) Harold C. Simmons Comprehensive Cancer Center (2019)
