Cancer cells frequently harbor complex genomes that are characterized by extensive DNA copy number changes and structural variation. The Ly Laboratory studies the mechanisms that give rise to genomic instability and chromosomal alterations in the context of human health and disease. Our team is currently interrogating the factors that shape the chaotic mutational landscape of cancer genomes, including the contributions from cell cycle regulation defects, chromosome segregation errors during cell division, and inaccurate DNA double-strand break repair pathways. We are particularly interested in the cellular and genetic basis of a diverse spectrum of genomic rearrangement types, including a class of complex and localized alterations known as chromothripsis. These rearrangements arise from the catastrophic fragmentation of individual chromosomes encapsulated into aberrant nuclear structures called micronuclei followed by the reassembly of broken DNA fragments in random order. Chromothripsis exemplifies a rapid mutational process in which tens to hundreds of genetic lesions can be generated within a few cell cycles.
Our research program employs a number of cutting-edge approaches bridging cell biology and genetics, including CRISPR-mediated genome editing, high-resolution live-cell microscopy, molecular cytogenetics, and whole-genome DNA sequencing. 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 numerical chromosomal alterations known as aneuploidy can trigger malignant transformation. He pursued postdoctoral training at the Ludwig Institute for Cancer Research and University of California San Diego with Don Cleveland. His postdoctoral research focused on reconstructing the mechanisms of complex structural genomic rearrangements using centromere inactivation and chromosome-specific mis-segregation approaches in human somatic cells. He was named a Hope Funds for Cancer Research Fellow and was the recipient of the NIH Pathway to Independence Award from the National Cancer Institute. In 2019, Dr. Ly joined the faculty of UT Southwestern Medical Center as a CPRIT Scholar in Cancer Research and Assistant Professor in the Department of Pathology. He also holds a secondary appointment in the Department of Cell Biology and is a member of the Harold C. Simmons Comprehensive Cancer Center. 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
- 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
- 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
- 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
- A PoleP286R mouse model of endometrial cancer recapitulates high mutational burden and immunotherapy response.
- Li HD, Lu C, Zhang H, Hu Q, Zhang J, Cuevas IC, Sahoo SS, Aguilar M, Maurais EG, Zhang S, Wang X, Akbay EA, Li GM, Li B, Koduru P, Ly P, Fu YX, Castrillon DH, JCI Insight 2020 Jul 5 14
- Cellular and genomic approaches for exploring structural chromosomal rearrangements.
- Hu Q, Maurais EG, Ly P, Chromosome Res. 2020 Jan
- TRIP13 and APC15 drive mitotic exit by turnover of interphase- and unattached kinetochore-produced MCC.
- Kim DH, Han JS, Ly P, Ye Q, McMahon MA, Myung K, Corbett KD, Cleveland DW Nat Commun 2018 Oct 9 1 4354
- 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
- Interrogating cell division errors using random and chromosome-specific missegregation approaches.
- Ly P, Cleveland DW Cell Cycle 2017 Jul 16 13 1252-1258
- CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly.
- Hoffmann S, Dumont M, Barra V, Ly P, Nechemia-Arbely Y, McMahon MA, Hervé S, Cleveland DW, Fachinetti D Cell Rep 2016 11 17 9 2394-2404
Honors & Awards
- Forbeck Scholar, William Guy Forbeck Research Foundation
- CPRIT Scholar in Cancer Research, Cancer Prevention & Research Institute of Texas
- 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)