Meet Gigi Lozano, Ph.D.
About Dr. Lozano
Guillermina (Gigi) Lozano is a renowned geneticist recognized for her studies of the p53 tumor suppressor pathway. This pathway is undermined in a large percent of human cancers via mutations and deletions of p53. Her laboratory identified a transcriptional activation function for p53. Using mouse models, her team characterized the physiological importance of Mdm2 and Mdm4 proteins as potent inhibitors of p53. The Mdm proteins are over expressed in many cancers that lack p53 mutations presenting an alternate mechanism of eliminating p53 activity. Other mouse models inheriting the most common p53 mutations revealed gain-of-function phenotypes that drive metastases.
Dr. Lozano received her BS degree in Biology and Mathematics, Magna Cum Laude, at the University of Texas Rio Grande Valley. She completed graduate studies at Rutgers University and the University of Medicine and Dentistry of New Jersey, and a post-doctoral fellowship with Dr. Arnold Levine at Princeton University.
Dr. Lozano was hired as an Instructor at The University of Texas MD Anderson Cancer Center in 1987 and quickly rose through the ranks to her current position as professor and chair of the department of Genetics. Dr. Lozano is a member of the National Academy of Sciences, the National Academy of Medicine and the American Academy of Arts and Sciences. She has received the Minorities in Cancer Research Jane Cooke Wright Lectureship and the Women in Cancer Research Charlotte Friend Lectureship awards both from the American Association for Cancer Research. She is also the recipient of distinguished alumni awards from both her undergraduate and graduate alma maters.
In the News
MD Anderson’s Guillermina Lozano elected to Fellows of the AACR Academy
MD Anderson genetics expert Guillermina Lozano elected to American Academy of Arts and Sciences
The p53 pioneer
MD Anderson genetics expert Guillermina Lozano elected to National Academy of Sciences
Hubert L. Olive Stringer Distinguished Chair in Oncology in Honor of Sue Gribble Stringer, Department of Genetics, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX
p53 pathway tumor suppressors mouse models
Mutation of the p53 gene is a critical event in the elaboration of many tumors of diverse origin. The p53 protein is activated in response to DNA damage, serving as a checkpoint in the elimination or repair of cells with damaged DNA. Alterations in components of the p53 pathway, such as amplification of the Mdm2 gene, which encodes a p53 inhibitor, also contribute to tumorigenesis. The overall goal of my laboratory is to understand the signals that regulate the p53 pathway and the consequences of expressing wild-type or mutant p53. Toward this goal, we are generating mouse models to address the importance of various p53 mutations in tumor development in vivo. The first mice generated were those expressing a common p53 mutation identified in human cancers. Mice expressing the p53R172H mutant develop osteosarcomas and carcinomas that metastasized at very high frequency. This study also indicates that mutant p53 is inherently unstable in vivo suggesting that other genetic alterations in tumor cells stabilize p53. We have generated mice with another interesting mutant that distinguishes the ability of p53 to induce apoptosis or cell cycle arrest. The p53R172P mutant cannot transactivate genes that induce apoptosis yet retains the ability to induce the p21 gene involved in cell cycle arrest. Importantly, this mutant shows delayed tumorigenesis suggesting that p53 activities other than apoptosis are also critical for tumor suppression. Tumors that arise in these mice are also genomically stable suggesting that the p53R172P mutant transactivates genes involved in maintaining a stable genome. Other mouse models generated probe the importance of components of the p53 pathway. For example, loss of Mdm2 or Mdm4 (genes that encode p53 inhibitors) results in embryonic lethality that is completely rescued by concomitant loss of p53. These studies indicate the importance of regulating p53 activity. We have made conditional loss-of-function allele of Mdm2 and Mdm4 to access the role of p53 in different cell types as a function of proliferation. Finally, we are studying individuals with Li-Fraumeni Syndrome, most of whom inherit a p53-missense mutation. Various factors including, modifiers of the p53 pathway alter the onset of tumorigenesis in these individuals.
View a complete list of Dr. Lozano's publications. Visit Dr. Lozano's Lab website. Follow Dr. Lozano on Twitter: @drgglozano View Dr. Lozano's publication highlights as reflected in Elsevier's Scopus database.
|1986||Rutgers University and the University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA, PHD, Biochemistry|
|1979||University of Texas Rio Grande Valley (formerly Pan American University), Edinburg, TX, USA, BS, Biology/Mathematics|
|1985-1987||Research Fellowship, Molecular Biology, Princeton University, Princeton, NJ|
Member, Cancer Early Detection Advance Research Center (CEDAR) Scientific Advisory Board (SAB), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 2222 - Present
Member, MD Anderson and UT Austin Executive Leadership, Houston, TX, 2022 - Present
Member, National Human Genome Research Institute (NHGRI), Board of Scientific Counselors, Bethesda, MD, 2021 - Present
Member, Stand Up To Cancer Joint Scientific Advisory Committee - Fanconi Anemia Research Fund – Farrah Fawcett Foundation Head and Neck Cancer Research Team Grant Program, Los Angeles, CA, 2020 - Present
Member, American Association for Cancer Research Nominating Committee, Philadelphia, PA, 2019 - 2021
Member, Stand Up To Cancer Health Equity Committee, Los Angeles, CA, 2019 - Present
Member, University of Washington, P01 External Advisory Board, (PI Ray Monnat), Seattle, WA, 2016 - 2021
Member, American Association for Cancer Research, Stand Up to Cancer Scientific Advisory Committee, Philadelphia, PA, 2012 - Present
Institutional Committee Activities
Member, Allison Institute Advisory Council (AIAC) for The James P. Allison Institute (JPAI), 2022 - Present
Member, CPRIT Single Cell Genomics Core, Internal Advisory Board, 2019 - Present
Member, CPRIT Internal Advisory Board, P.I. Jonathan Kurie, 2016 - Present
Member, Women and Minority Faculty Inclusion, Advisory Committee, 2016 - Present
Member, Blaffer Steering Committee, 2007 - Present
|2022||The John Mendelsohn Award for Faculty Leadership, The University of Texas MD Anderson Cancer Center|
|2021||Fellow, American Association for Cancer Research Academy|
|2020||Member, American Academy of Arts and Sciences|
|2018||Hubert L. Olive Stringer Distinguished Chair in Oncology in Honor of Sue Gribble Stringer, The University of Texas MD Anderson Cancer Center Endowment|
|2017||Member, National Academy of Sciences|
|2014||Member, National Academy of Medicine (formerly Institute of Medicine)|
|2014||Member, The Academy of Medicine, Engineering and Science of Texas|
|2011||Fellow, American Association for the Advancement of Science|
|1994||The 1994 Faculty Achievement Award in Basic Research, The University of Texas MD Anderson Cancer Center|
|1990||Outstanding Faculty Award, The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences|
- Sun C, Estrella JS, Whitley EM, Chau GP, Lozano G, Wasylishen AR. Context matters - Daxx and Atrx are not robust tumor suppressors in the murine endocrine pancreas. Dis Model Mech 15(8), 2022. e-Pub 2022. PMID: 35976056.
- Barton MC, Lozano G. p53 Activation Paradoxically Causes Liver Cancer. Cancer Res 82(16):2824-2825, 2022. PMID: 35971677.
- Shah VV, Duncan AD, Jiang S, Stratton SA, Allton KL, Yam C, Jain A, Krause PM, Lu Y, Cai S, Tu Y, Zhou X, Zhang X, Jiang Y, Carroll CL, Kang Z, Liu B, Shen J, Gagea M, Manu SM, Huo L, Gilcrease M, Powell RT, Guo L, Stephan C, Davies PJ, Parker-Thornburg J, Lozano G, Behringer RR, Piwnica-Worms H, Chang JT, Moulder SL, Barton MC. Mammary-specific expression of Trim24 establishes a mouse model of human metaplastic breast cancer. Nat Commun 12(1):5389, 2021. e-Pub 2021. PMID: 34508101.
- Perez EA, Jaffee EM, Whyte J, Boyce CA, Carpten JD, Lozano G, Williams RM, Winkfield KM, Bernstein D, Poblete S. Analysis of Population Differences in Digital Conversations About Cancer Clinical Trials: Advanced Data Mining and Extraction Study. JMIR Cancer 7(3):e25621, 2021. e-Pub 2021. PMID: 34554099.
- Kim MP, Li X, Deng J, Zhang Y, Dai B, Allton KL, Hughes TG, Siangco C, Augustine JJ, Kang Y, McDaniel JM, Xiong S, Koay EJ, McAllister F, Bristow CA, Heffernan TP, Maitra A, Liu B, Barton MC, Wasylishen AR, Fleming JB, Lozano G. Oncogenic KRAS recruits an expansive transcriptional network through mutant p53 to drive pancreatic cancer metastasis. Cancer Discov 11(8):2094-2111, 2021. e-Pub 2021. PMID: 33839689.
- Jeffers JR, Pinto EM, Rehg JE, Clay MR, Wang J, Neale G, Heath RJ, Lozano G, Lalli E, Figueiredo BC, Pappo AS, Rodriguez-Galindo C, Chen W, Pounds S, Ribeiro RC, Zambetti GP. The Common Germline TP53-R337H Mutation is Hypomorphic and Confers Incomplete Penetrance and Late Tumor Onset in a Mouse Model. Cancer Res 81(9):2442-2456, 2021. e-Pub 2021. PMID: 33637564.
- Zhou X, Beilter A, Xu Z, Gao R, Xiong S, Paulucci-Holthauzen A, Lozano G, de Crombrugghe B, Gorlick R. Wnt/ß-catenin-mediated p53 suppression is indispensable for osteogenesis of mesenchymal progenitor cells. Cell Death Dis 12(6):521, 2021. e-Pub 2021. PMID: 34021120.
- Ueda K, Kumari R, Schwenger E, Wheat JC, Bohorquez O, Narayanagari SR, Taylor SJ, Carvajal LA, Pradhan K, Bartholdy B, Todorova TI, Goto H, Sun D, Chen J, Shan J, Song Y, Montagna C, Xiong S, Lozano G, Pellagatti A, Boultwood J, Verma A, Steidl U. MDMX acts as a pervasive preleukemic-to-acute myeloid leukemia transition mechanism. Cancer Cell 39(21):00108-2, 2021. e-Pub 2021. PMID: 33667384.
- Wasylishen AR, Sun C, Moyer SM, Qi Y, Chau GP, Aryal NK, McAllister F, Kim MP, Barton MC, Estrella JS, Su X, Lozano G. Daxx maintains endogenous retroviral silencing and restricts cellular plasticity in vivo. Sci Adv 6(32):eaba8415, 2020. e-Pub 2020. PMID: 32821827.
- Wasylishen AR, Sun C, Chau GP, Qi Y, Su X, Kim MP, Estrella JS, Lozano G. Men1 maintains exocrine pancreas homeostasis in response to inflammation and oncogenic stress. Proc Natl Acad Sci U S A 117(12):6622-6629, 2020. e-Pub 2020. PMID: 32156729.
- Pant V, Xiong S, Wasylishen AR, Larsson CA, Aryal NK, Chau G, Tailor RC, Lozano G. Transient enhancement of p53 activity protects from radiation-induced gastrointestinal toxicity. Proc Natl Acad Sci U S A 116(35):17429-17437, 2019. e-Pub 2019. PMID: 31409715.
- Zhang Y, Xiong S, Liu B, Pant V, Celii F, Chau G, Elizondo-Fraire AC, Yang P, You MJ, El-Naggar AK, Navin NE, Lozano G. Somatic Trp53 mutations differentially drive breast cancer and evolution of metastases. Nat Commun 9(1):3953, 2018. e-Pub 2018. PMID: 30262850.
- Larsson CA, Moyer SM, Liu B, Michel KA, Pant V, Yang P, Wong J, El-Naggar AK, Krahe R, Lozano G. Synergistic and additive effect of retinoic acid in circumventing resistance to p53 restoration. Proc Natl Acad Sci U S A 115(9):2198-2203, 2018. e-Pub 2018. PMID: 29440484.
- Pourebrahim R, Zhang Y, Liu B, Gao R, Xiong S, Lin PP, McArthur MJ, Ostrowski MC, and Lozano G.. Integrative genome analysis of somatic p53 mutant osteosarcomas identifies Ets2-dependent regulation of small nucleolar RNAs by mutant p53. Genes & Dev 31(18):1847-1857, 2017. PMID: 29021240.
- Xiong S, Tu H, Kollareddy M, Pant V, Li Q, Zhang Y, Jackson JG, Suh YA, Elizondo-Fraire AC, Yang P, Chau G, Tashakori M, Wasylishen AR, Ju Z, Solomon H, Rotter V, Liu B, El-Naggar AK, Donehower LA, Martinez LA, Lozano G. Pla2g16 phospholipase mediates gain-of-function activities of mutant p53. Proc Natl Acad Sci USA 111(30):11145-11150, 2014.
- Pant V, Xiong S, Jackson JG, Post SM, Abbas HA, Quintás-Cardama A, Hamir AN, Lozano G. The p53-Mdm2 feedback loop protects against DNA damage by inhibiting p53 activity but is dispensable for p53 stability, development and longevity. Genes Dev 27(17):1857-1867, 2013. e-Pub 2013. PMID: 23973961.
- Jackson JG, Pant V, Li Q, Chang LL, Quintás-Cardama A, Garza D, Tavana O, Yang P, Manshouri T, Li Y, El-Naggar AK, Lozano G. p53 mediated senescence impairs the apoptotic response to chemotherapy and clinical outcome in breast cancer. Cancer Cell 21(6):793-806, 2012. PMID: 22698404.
- Pant V, Xiong S, Iwakuma T, Quintás-Cardama A, Lozano G. Heterodimerization of Mdm2 and Mdm4 is critical for regulating p53 activity during embryogenesis but dispensable for p53 and Mdm2 stability. Proc Natl Acad Sci USA 108(29):1995-2000, 2011. e-Pub 2011. PMID: 21730132.
- Suh YA, Post SM, Elizondo-Fraire AC, Maccio DR, Jackson JG, El-Naggar AK, Van Pelt C, Terzian T, Lozano G. Multiple stress signals activate mutant p53 in vivo. Cancer Res 71(23):7168-7175, 2011.
- Abbas HA, Maccio DR, Coskun S, Jackson JG, Hazen AL, Sills TM, You MJ, Hirschi KK, Lozano G. Mdm2 is required for survival of hematopoietic stem cells/progenitors via dampening of ROS-induced p53 activity. Cell Stem Cell 7(5):606-617, 2010. PMID: 21040902.
- Post SM, Quintas-Cardama A, Pant V, Iwakuma T, Hamir A, Jackson JG, Maccio DR, Bond GL, Johnson DG, Levine AJ, Lozano G. A high-frequency regulatory polymorphism in the p53 pathway accelerates tumor development. Cancer Cell 18(3):220-230, 2010.
- Xiong S, Pant V, Suh YA, Van Pelt CS, Wang Y, Valentin-Vega YA, Post SM, Lozano G. Spontaneous tumorigenesis in mice overexpressing the p53-negative regulator Mdm4. Cancer Res 70(18):7148-7154, 2010. PMID: 20736370.
- Terzian T, Suh YA, Iwakuma T, Post SM, Neumann M, Lang GA, Van Pelt CS, Lozano G. The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss. Genes Dev 22(10):1337-1344, 2008.
- Barboza JA, Liu G, Ju Z, El-Naggar AK, Lozano G. p21 delays tumor onset by preservation of chromosomal stability. Proc Natl Acad Sci USA 103(52):19842-19847, 2006. e-Pub 2006. PMID: 17170138.
- Lang GA, Iwakuma T, Suh YA, Liu G, Rao VA, Parant JM, Valentin-Vega YA, Terzian T, Caldwell LC, Strong LC, El-Naggar AK, Lozano G. Gain-of-function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell 119(6):861-872, 2004.
- Liu G, Parant JM, Lang G, Chau P, Chavez-Reyes A, El-Naggar AK, Multani A, Chang S, Lozano G. Chromosome stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice. Nat Genet 36(1):63-68, 2004. e-Pub 2003. PMID: 14702042.
- Parant J, Chavez-Reyes A, Little NA, Yan W, Reinke V, Jochemsen AG, Lozano G. Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53. Nat Genet 29(1):92-95, 2001. PMID: 11528400.
- Montes de Oca Luna R, Wagner DS, Lozano G. Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 378(6553):203-206, 1995. PMID: 7477326.
- Raycroft L, Wu HY, Lozano G. Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene. Science 249(4972):1049-1051, 1990. PMID: 2144364.
- Ding J, Li X, Khan S, Zhang C, Gao F, Sen S, Wasylishen AR, Zhao Y, Lozano G, Koul D, Yung WKA. EGFR suppresses p53 function by promoting p53 binding to DNA-PKcs: a non-canonical regulatory axis between EGFR and wild-type p53 in glioblastoma. Neuro Oncol. e-Pub 2022. PMID: 35474131.
- Xiong S, Chachad D, Zhang Y, Gencel-Augusto J, Sirito M, Pant V, Yang P, Sun C, Chau G, Qi Y, Su X, Whitley EM, El-Naggar AK, Lozano G. Differential gain-of-function activity of three p53 hotspot mutants in vivo. Cancer Res. e-Pub 2022. PMID: 35320355.
- Pant V, Aryal NK, Xiong S, Chau GP, Fowlkes NW, Lozano G. Alterations of the MDM2 C-terminus differentially impact its function in vivo. Cancer Res. e-Pub 2022. PMID: 35078816.
- Moyer SM, Wasylishen AR, Qi Y, Fowlkes N, Su X, Lozano G. p53 drives a transcriptional program that elicits a non-cell-autonomous response and alters cell state in vivo. Proc Natl Acad Sci U S A 117(38):23663-23673. e-Pub 2020. PMID: 32900967.
- Gencel-Augusto J, Lozano G. p53 tetramerization: at the center of the dominant-negative effect of mutant p53. Genes Dev 34(17-18):1128-1146, 2020. PMID: 32873579.
- Lozano G. Restoring p53 in cancer: the promises and the challenges. J Mol Cell Biol 11(7):615-619, 2019. e-Pub 2019. PMID: 31283825.
- Lozano G. One step at a time. Mol Biol Cell 29(22):2614-2615, 2018. PMID: 30376433.
- Kim MP, Lozano G. Mutant p53 partners in crime. Cell Death Differ 25(1):161-168, 2018. e-Pub 2017. PMID: 29099488.
- Zhang Y, Lozano G. p53: multiple facets of a rubik’s cube. Cancer Biol 1:185-201, 2017. PMID: 30775651.
- Jackson JG, Lozano G. TNBC invasion: downstream of STAT3. Oncotarget 8(13):20517-20518, 2017. PMID: 28199968.
- Kim MP, Zhang Y, Lozano G. Mutant p53: Multiple Mechanisms Define Biologic Activity in Cancer. Front Oncol 5:249, 2015. e-Pub 2015. PMID: 26618142.
- Pant V, Lozano G. Dissecting the p53-Mdm2 feedback loop in vivo: uncoupling the role in p53 stability and activity. Oncotarget 5:1149-1156, 2014.
- Pant V, Lozano G. Limiting the power of p53 through the ubiquitin proteasome pathway. Genes Dev 28(16):1739-1751, 2014.
- Jackson JG, Lozano G. Che-ating death: Che1/AATF protects from p53 mediated apoptosis. EMBO J 31(20):3951-3953, 2012. e-Pub 2012. PMID: 22960635.
- Xiong S, Parker-Thornburg J, Lozano G. Developing genetically engineered mouse models to study tumor suppression. Curr Protoc Mouse Biol 2(1):9-24, 2012. PMID: 22582146.
- Jackson J, Lozano G. The mutant p53 mouse as a pre-clinical model. Oncogene:doi:10. 1038/onc. 610, 2012.
- Riley MF, Lozano G. The many faces of MDM2 binding partners. Genes Cancer 3(3-4):226-239, 2012. PMID: 23150756.
- Post SM, Lozano G. You can win by losing: p53 mutations in rhabdomyosarcoma. J Pathology 222(2):124-128, 2010. PMID: 20801751.
- Lozano G. The oncogenic roles of p53 mutants in mouse models. Curr Opin Genet Dev 17(1):66-70, 2007. PMID: 17208429.
- Iwakuma T, Lozano G, Flores ER. Li-Fraumeni syndrome: a p53 family affair. Cell Cycle 4(7):41-43, 2005. PMID: 15917654.
- Lozano G, Zambetti GP. What have animal models taught us about the p53 pathway?. J Pathol 205(2):206-220, 2005. PMID: 15643668.
- Iwakuma T, Lozano G. MDM2, an introduction. Mol Cancer Res 1:993-1000, 2003. PMID: 14707282.
- Morrissey RL, Thompson AM, Lozano G. Is loss of p53 a driver of ductal carcinoma in situ progression?. Br J Cancer. e-Pub 2022. PMID: 35764786.
|Title:||Cancer Center Support Grant, Cancer Genetics and Epigenetics|
|Title:||Cancer Center Support Grant, Genetically Engineered Mouse Facility (GEMF)|
|Title:||Role of p53 Missense Mutations on Tumorigenesis in Vivo|
|Title:||(PQ4) Mutations in the histone chaperone DAXX drive pancreatic neuroendocrine|
|Title:||Identifying vulnerabilities in mutant p53 driven tumorigenesis|
|Funding Source:||Cancer Prevention & Research Institute of Texas (CPRIT)|
|Title:||Defining diverse roles of p53 in pancreatic cancer|
|Title:||Upgrade for Nikon Confocal: LUNV Laser Launch and DU-G|
|Title:||A somatic mutant p53 mouse model of metastatic triple negative breast cancer|
|Funding Source:||Cancer Prevention & Research Institute of Texas (CPRIT)|
|Title:||The roles of TRIM24 in breast cancer|
|Title:||Identifying cooperating lesions of Mdm4/mutant p53 driven breast cancer and resistance mechanisms to Mdm4 inhibition|
|Funding Source:||Sister Institution Network Fund|
|Title:||Identifying vulnerabilities in p53 mutant tumors|
|Funding Source:||Brockman Foundation|
|Title:||Understanding the physiologically relevant functions of Daxx|
|Funding Source:||The Neuroendocrine Tumor Research Foundation (NETRF)|
|Title:||Dissecting the source and mechanisms of IL-17-mediated modulation of pancreatic tumorigenesis|
|Title:||Identifying the vulnerabilities in Mdm2 overexpressing cancer cells|
|Title:||A Pathway of Tumor Suppression|
|Title:||Role of p53 missense mutations on tumorigenesis in vivo|
|Funding Source:||The Anna Fuller Fund|