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 pulverization 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. The accumulation of massive DNA damage within micronuclei triggers the mis-segregated chromosome to catastrophically shatter into tens to hundreds of genomic fragments. Attempts by error-prone DNA repair pathways to reassemble the shattered fragments together often 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 and tumorigenesis.
Our research program employs a number of interdisciplinary approaches bridging cell biology and genetics, including CRISPR/Cas9 screens, high-resolution fixed- and live-cell microscopy, molecular 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 earned his 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, can promote malignant transformation. He pursued postdoctoral training at the University of California San Diego and Ludwig Institute for Cancer Research with Don Cleveland. His postdoctoral research focused on reconstructing the mechanisms of complex structural genomic rearrangements using chromosome-specific mis-segregation approaches 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.
- Cell cycle and cell division
- Chromosome rearrangements
- DNA damage response and repair
- Genomic instability in cancer
- Mechanisms of chromothripsis
- Non-homologous end joining shapes the genomic rearrangement landscape of chromothripsis from mitotic errors.
- Hu Q, Espejo Valle-Inclan J, Dahiya R, Guyer A, Mazzagatti A, Maurais EG, Engel JL, Cortés-Ciriano I, Ly P, bioRxiv 2023 Aug
- 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
- Selective Y centromere inactivation triggers chromosome shattering in micronuclei and repair by non-homologous end joining.
- Ly P, Teitz LS, Kim DH, Shoshani O, Skaletsky H, Fachinetti D, Page DC, Cleveland DW Nat. Cell Biol. 2017 Jan 19 1 68-75
- SETD2 safeguards the genome against isochromosome formation.
- Mason FM, Kounlavong ES, Tebeje AT, Dahiya R, Guess T, Khan A, Vlach L, Norris SR, Lovejoy CA, Dere R, Strahl BD, Ohi R, Ly P, Walker CL, Rathmell WK, Proc Natl Acad Sci U S A 2023 Sep 120 39 e2303752120
- Epigenetic dysregulation from chromosomal transit in micronuclei.
- Agustinus AS, Al-Rawi D, Dameracharla B, Raviram R, Jones BSCL, Stransky S, Scipioni L, Luebeck J, Di Bona M, Norkunaite D, Myers RM, Duran M, Choi S, Weigelt B, Yomtoubian S, McPherson A, Toufektchan E, Keuper K, Mischel PS, Mittal V, Shah SP, Maciejowski J, Storchova Z, Gratton E, Ly P, Landau D, Bakhoum MF, Koche RP, Sidoli S, Bafna V, David Y, Bakhoum SF, Nature 2023 Jun
Honors & Awards
- American Cancer Society - Institutional Research Grant Award
- Early-Career Investigator, DoD Academy of Kidney Cancer Investigators
- UT Southwestern Haberecht Wildhare-Idea Research Award
- UT Southwestern Circle of Friends Research Award
- CPRIT Scholar in Cancer Research, Cancer Prevention & Research Institute of Texas
- Forbeck Scholar, William Guy Forbeck Research Foundation
- James Kerr Award for Research Excellence, Ludwig Institute for Cancer Research
- NIH/NCI Pathway to Independence Award (K99/R00)
- Hope Funds for Cancer Research Fellow
- NIH/NCI Cancer Cell Biology Postdoctoral Training Grant Award
- CPRIT Predoctoral Training Grant Award, Cancer Prevention & Research Institute of Texas
- Jack G. and Norma Jean Folmar Research Scholarship, Baylor University
- Rubin and Sarah Shaps Scholar, Memorial Sloan-Kettering Cancer Center
- American Society for Cell Biology (2013)
- Harold C. Simmons Comprehensive Cancer Center (2019)