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
- 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
- MYC Is a Major Determinant of Mitotic Cell Fate.
- Topham C, Tighe A, Ly P, Bennett A, Sloss O, Nelson L, Ridgway RA, Huels D, Littler S, Schandl C, Sun Y, Bechi B, Procter DJ, Sansom OJ, Cleveland DW, Taylor SS Cancer Cell 2015 Jul 28 1 129-40
- DNA Sequence-Specific Binding of CENP-B Enhances the Fidelity of Human Centromere Function.
- Fachinetti D, Han JS, McMahon MA, Ly P, Abdullah A, Wong AJ, Cleveland DW Dev. Cell 2015 May 33 3 314-27
- Mitigation of Radiation-Induced Damage by Targeting EGFR in Noncancerous Human Epithelial Cells.
- Kim SB, Ly P, Kaisani A, Zhang L, Wright WE, Shay JW Radiat. Res. 2013 Aug
- Cavin-3 dictates the balance between ERK and Akt signaling.
- Hernandez VJ, Weng J, Ly P, Pompey S, Dong H, Mishra L, Schwarz M, Anderson RG, Michaely P Elife 2013 2 e00905
- RNAi screening of the human colorectal cancer genome identifies multifunctional tumor suppressors regulating epithelial cell invasion.
- Ly P, Eskiocak U, Parker CR, Harris KJ, Wright WE, Shay JW Cell Res. 2012 Nov 22 11 1605-8
- Targeting of Nrf2 induces DNA damage signaling and protects colonic epithelial cells from ionizing radiation.
- Kim SB, Pandita RK, Eskiocak U, Ly P, Kaisani A, Kumar R, Cornelius C, Wright WE, Pandita TK, Shay JW Proc. Natl. Acad. Sci. U.S.A. 2012 Oct 109 43 E2949-55
- Aneuploid human colonic epithelial cells are sensitive to AICAR-induced growth inhibition through EGFR degradation.
- Ly P, Kim SB, Kaisani AA, Marian G, Wright WE, Shay JW Oncogene 2012 Aug
- Functional parsing of driver mutations in the colorectal cancer genome reveals numerous suppressors of anchorage-independent growth.
- Eskiocak U, Kim SB, Ly P, Roig AI, Biglione S, Komurov K, Cornelius C, Wright WE, White MA, Shay JW Cancer Res. 2011 Jul 71 13 4359-65
- Characterization of aneuploid populations with trisomy 7 and 20 derived from diploid human colonic epithelial cells.
- Ly P, Eskiocak U, Kim SB, Roig AI, Hight SK, Lulla DR, Zou YS, Batten K, Wright WE, Shay JW Neoplasia 2011 Apr 13 4 348-57
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)