E. Paul Hasty, DVM

Professor

Education

Year	Degree	Discipline	Institution
1985	BS	Veterinary Medicine	Texas A&M University College Station , TX
1987	DVM	Veterinary Medicine	Texas A&M University College Station , TX
	Postdoctoral Fellowship	Molecular Medicine	Institute for Human and Molecular Genetics, Baylor College of Medicine Houston , TX

Research

We focus on the impact chromatin metabolism has on cancer and aging in genetically altered cells mice using embryonic stem cell/gene targeting technology. Specifically we study proteins important for the repair of DNA double – strand breaks by two different pathways. The first pathway is called recombinational repair by virtue that it utilizes a homologous template usually provided by the sister chromatid. To disrupt recombinational repair, we mutated Rad51 and found it to be essential for cellular proliferation and repair of DNA damaged by ionizing radiation. rad51 – mutant embryos die shortly after implantation. Next we determined that a cell cycle response contributed to embryonic lethality by crossing the rad51 – mutant mice to p53 – mutant mice. p53 is a tumor suppressor that is essential for stopping cellular proliferation after DNA damage. We also discovered that Rad51 functions by binding to a breast cancer susceptibility gene called Brca2 and mice with a subtle brca2 mutation exhibit a shortened life span due to increased cancer incidence. Thus, we established that the Rad51 pathway is important for suppressing tumors. The second pathway is called nonhomologus end joining (NHEJ) because it joins chromosomal ends without the use of a homologous template. To disrupt NHEJ, we mutated Ku80 (a.k.a. Ku86) and found that ku80 – mutant mice are relatively normal at birth; however, exhibit an early onset of characteristics associated with aging that include osteopenia, skin and follicular atrophy, liver degeneration and shortened life span. Early onset of sepsis and cancer shortened life span. In addition, cells derived from ku80 – mutant mice undergo premature cellular senescence that is dependent on the tumor suppressor protein p53. Ongoing research focuses on the molecular mechanisms important for both DNA repair pathways with special attention to aging and oncogenesis.

Awards & Accomplishments

1985	The National Dean’s List
1988	Postdoctoral Research Fellow of Granada Corporation
1990	Postdoctoral Research Fellow of the Cystic Fibrosis Foundation
1993	March of Dimes Basil O’Connor Scholar

Publications

1.	Baroni, M., Yi, C., Choudhary, S., Lei, X., Kosti, A., Grieshober, D., Velasco, M., Qiao, M., Burns, S. S., Araujo, P. R., Delambre, T., Son, M. Y., Plateroti, M., Ferreira, M. A. R., Hasty, P., & Penalva, L. O. F. (2021). Musashi1 contribution to glioblastoma development via regulation of a network of dna replication, cell cycle and division genes. Cancers, 13(7), [1494]. https://doi.org/10.3390/cancers13071494
2.	Tichy, E. D., Ma, N., Sidibe, D., Loro, E., Kocan, J., Chen, D. Z., Khurana, T. S., Hasty, P., & Mourkioti, F. (2021). Persistent NF-κB activation in muscle stem cells induces proliferation-independent telomere shortening. Cell Reports, 35(6), [109098]. https://doi.org/10.1016/j.celrep.2021.109098
3.	Parihar, M., Dodds, S. G., Hubbard, G., Javors, M. A., Strong, R., Hasty, P., & Sharp, Z. D. (2021). Rapamycin Extends Life Span in ApcMin/+ Colon Cancer FAP Model. Clinical Colorectal Cancer, 20(1), e61-e70. https://doi.org/10.1016/j.clcc.2020.08.006
4.	Hasty, P. (2021). Trex2 responds to damaged replication forks in diverse ways. Molecular and Cellular Oncology, 8(2), [1881394]. https://doi.org/10.1080/23723556.2021.1881394
5.	Dodds, S. G., Parihar, M., Javors, M., Nie, J., Musi, N., Dave Sharp, Z., & Hasty, P. (2020). Acarbose improved survival for Apc+/Min mice. Aging cell, 19(2), [e13088]. https://doi.org/10.1111/acel.13088
6.	Kim, D. E., Dollé, M. E. T., Vermeij, W. P., Gyenis, A., Vogel, K., Hoeijmakers, J. H. J., Wiley, C. D., Davalos, A. R., Hasty, P., Desprez, P. Y., & Campisi, J. (2020). Deficiency in the DNA repair protein ERCC1 triggers a link between senescence and apoptosis in human fibroblasts and mouse skin. Aging cell, 19(3), [e13072]. https://doi.org/10.1111/acel.13072
7.	Ko, J. H., Son, M. Y., Zhou, Q., Molnarova, L., Song, L., Mlcouskova, J., Jekabsons, A., Montagna, C., Krejci, L., & Hasty, P. (2020). TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51K133A. Cell Reports, 33(12), [108543]. https://doi.org/10.1016/j.celrep.2020.108543
8.	Seol, J. H., Holland, C., Li, X., Kim, C., Li, F., Medina-Rivera, M., Eichmiller, R., Gallardo, I. F., Finkelstein, I. J., Hasty, P., Shim, E. Y., Surtees, J. A., & Lee, S. E. (2018). Distinct roles of XPF-ERCC1 and Rad1-Rad10-Saw1 in replication-coupled and uncoupled inter-strand crosslink repair. Nature communications, 9(1), [2025]. https://doi.org/10.1038/s41467-018-04327-0
9.	Willis, N. A., Frock, R. L., Menghi, F., Duffey, E. E., Panday, A., Camacho, V., Hasty, E. P., Liu, E. T., Alt, F. W., & Scully, R. (2017). Mechanism of tandem duplication formation in BRCA1-mutant cells. Nature, 551(7682), 590-595. https://doi.org/10.1038/nature24477
10.	Dodds, S. G., Livi, C. B., Parihar, M., Hsu, H. K., Benavides, A. D., Morris, J., Javors, M., Strong, R., Christy, B., Hasty, P., & Sharp, Z. D. (2016). Adaptations to chronic rapamycin in mice. Pathobiology of Aging and Age-related Diseases, 6, [31688]. https://doi.org/10.3402/pba.v6.31688
11.	Son, M. Y., Deng, C. X., Hoeijmarkers, J. H., Rebel, V. I., & Hasty, P. (2016). A mechanism for 1,4-Benzoquinone-induced genotoxicity. Oncotarget, 7(29), 46433-46447. https://doi.org/10.18632/oncotarget.10184
12.	Hasty, E. P. (2016). Editorial. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 788, 1. https://doi.org/10.1016/j.mrfmmm.2016.05.003
13.	Ngo, J., Matsuyama, M., Kim, C., Poventud-Fuentes, I., Bates, A., Siedlak, S. L., Lee, H. G., Doughman, Y. Q., Watanabe, M., Liner, A., Hoit, B., Voelkel, N., Gerson, S., Hasty, P., & Matsuyama, S. (2015). Bax deficiency extends the survival of ku70 knockout mice that develop lung and heart diseases. Cell Death and Disease, 6(3), 1-12. [e1706]. https://doi.org/10.1038/cddis.2015.11
14.	Hurez, V., Dao, V., Liu, A., Pandeswara, S., Gelfond, J., Sun, L., Bergman, M., Orihuela, C. J., Galvan, V., Padrón, Á., Drerup, J., Liu, Y., Hasty, P., Sharp, Z. D., & Curiel, T. J. (2015). Chronic mTOR inhibition in mice with rapamycin alters T, B, myeloid, and innate lymphoid cells and gut flora and prolongs life of immune-deficient mice. Aging cell, 14(6), 945-956. https://doi.org/10.1111/acel.12380
15.	Christy, B., Demaria, M., Campisi, J., Huang, J., Jones, D., Dodds, S. G., Williams, C., Hubbard, G., Livi, C. B., Gao, X., Weintraub, S., Curiel, T., Sharp, Z. D., & Hasty, P. (2015). P53 and rapamycin are additive. Oncotarget, 6(18), 15802-15813. https://doi.org/10.18632/oncotarget.4602
16.	Dao, V., Pandeswara, S., Liu, Y., Hurez, V., Dodds, S., Callaway, D., Liu, A., Hasty, P., Sharp, Z. D., & Curiel, T. J. (2015). Prevention of carcinogen and inflammation-induced dermal cancer by oral rapamycin includes reducing genetic damage. Cancer Prevention Research, 8(5), 400-409. https://doi.org/10.1158/1940-6207.CAPR-14-0313-T
17.	Kim, T. M., Son, M. Y., Dodds, S., Hu, L., Luo, G., & Hasty, P. (2015). RECQL5 and BLM exhibit divergent functions in cells defective for the Fanconi anemia pathway. Nucleic acids research, 43(2), 893-903. https://doi.org/10.1093/nar/gku1334
18.	Kim, T. M., Son, M. Y., Dodds, S., Hu, L., & Hasty, P. (2014). Deletion of BRCA2 exon 27 causes defects in response to both stalled and collapsed replication forks. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 766-767, 66-72. https://doi.org/10.1016/j.mrfmmm.2014.06.003
19.	Choi, Y. J., Li, H., Son, M. Y., Wang, X. H., Fornsaglio, J. L., Sobol, R. W., Lee, M., Vijg, J., Imholz, S., Dollé, M. E. T., Van Steeg, H., Reiling, E., & Hasty, P. (2014). Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair. PloS one, 9(1), [e86358]. https://doi.org/10.1371/journal.pone.0086358
20.	Hasty, P., Livi, C. B., Dodds, S. G., Jones, D., Strong, R., Javors, M., Fischer, K. E., Sloane, L., Murthy, K., Hubbard, G., Sun, L., Hurez, V., Curiel, T. J., & Sharp, Z. D. (2014). ERapa restores a normal life span in a FAP mouse model. Cancer Prevention Research, 7(1), 169-178. https://doi.org/10.1158/1940-6207.CAPR-13-0299
21.	Nair, B. C., Krishnan, S. R., Sareddy, G. R., Mann, M., Xu, B., Natarajan, M., Hasty, P., Brann, D., Tekmal, R. R., & Vadlamudi, R. K. (2014). Proline, glutamic acid and leucine-rich protein-1 is essential for optimal p53-mediated DNA damage response. Cell Death and Differentiation, 21(9), 1409-1418. https://doi.org/10.1038/cdd.2014.55
22.	Reiling, E., Dollé, M. E. T., Youssef, S. A., Lee, M., Nagarajah, B., Roodbergen, M., De With, P., De Bruin, A., Hoeijmakers, J. H., Vijg, J., Van Steeg, H., & Hasty, P. (2014). The progeroid phenotype of Ku80 deficiency Is dominant over DNA-PK CS deficiency. PloS one, 9(4), [e93568]. https://doi.org/10.1371/journal.pone.0093568
23.	Maslov, A. Y., Ganapathi, S., Westerhof, M., Quispe-Tintaya, W., White, R. R., Van Houten, B., Reiling, E., Dollé, M. E. T., van Steeg, H., Hasty, P., Hoeijmakers, J. H. J., & Vijg, J. (2013). DNA damage in normally and prematurely aged mice. Aging cell, 12(3), 467-477. https://doi.org/10.1111/acel.12071
24.	Gravina, S., Dollé, M. E. T., Wang, T., van Steeg, H., Hasty, P., Hoeijmakers, J., & Vijg, J. (2013). High Preservation of CpG Cytosine Methylation Patterns at Imprinted Gene Loci in Liver and Brain of Aged Mice. PloS one, 8(9), [e73496]. https://doi.org/10.1371/journal.pone.0073496
25.	Li, H., Marple, T., & Hasty, P. (2013). Ku80-deleted cells are defective at base excision repair. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 745-746, 16-25. https://doi.org/10.1016/j.mrfmmm.2013.03.010
26.	Livi, C. B., Hardman, R. L., Christy, B. A., Dodds, S. G., Jones, D., Williams, C., Strong, R., Bokov, A., Javors, M. A., Ikeno, Y., Hubbard, G., Hasty, P., & Sharp, Z. D. (2013). Rapamycin extends life span of Rb1+/- mice by inhibiting neuroendocrine tumors. Aging, 5(2), 100-110. https://doi.org/10.18632/aging.100533
27.	Hu, L., Kim, T. M., Son, M. Y., Kim, S. A., Holland, C. L., Tateishi, S., Kim, D. H., Yew, P. R., Montagna, C., Dumitrache, L. C., & Hasty, P. (2013). Two replication fork maintenance pathways fuse inverted repeats to rearrange chromosomes. Nature, 501(7468), 569-572. https://doi.org/10.1038/nature12500

https://scholars.uthscsa.edu/en/persons/edward-p-hasty