Developed the C-banding technique for labeling chromosomes, enabling scientists to pinpoint the precise location of genes in various chromosomes.
Arrighi FE, Hsu TC. Localization of heterochromatin in human chromosomes. Cytogenetics 10:81-86, 1971.
Demonstrated that particular unstable sections of a DNA molecule can become deformed, producing mutations and chromosomal breaks in the absence of external chemical agents, thus discovering a new way that cancer-causing genes can be produced.
Wang G, Christensen LA, Vasquez KM. Z-DNA-forming sequences generate large-scale deletions in mammalian cells. Proc Natl Acad Sci U S A. 2006;103(8):2677-2682.
Wang G, Vasquez KM. Naturally occurring H-DNA-forming sequences are mutagenic in mammalian cells. Proc Natl Acad Sci U S A. 2004;101(37):13448-13453.
Demonstrated that p53, the most prevalent cancer-causing gene, acts differently depending on whether it is deleted or has specific mutations in its DNA sequence.
Lang GA, Iwakuma T, Suh YA, Liu G, Rao VA, Parant JM, Valentin-Vega YA, Terzian T, Caldwell LC, Strong LC, El-Naggar AK and Lozano G. Gain-of-function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell. 2004;119:861-872.
Discovered that colon cancers in patients from different geographic areas are different because different genes are being mutated or abnormally regulated.
Soliman AS, Bondy ML, El-Badawy SA, Mokhtar N, Eissa S, Bayoumy S, Seifeldin IA, Houlihan PS, Lukish JR, Watanabe T, Chan AO, Zhu D, Amos CI, Levin B, Hamilton SR. Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients. Br J Cancer. 2001;85:1037-1046.
Chan AO, Soliman AS, Zhang Q, Rashid A, Bedeir A, Houlihan PS, Mokhtar N, Al-Masri N, Ozbek U, Yaghan R, Kandilci A, Omar S, Kapran Y, Dizdaroglu F, Bondy ML, Amos CI, Issa JP, Levin B, Hamilton SR. Differing DNA methylation patterns and gene mutation frequencies in colorectal carcinomas from Middle Eastern countries. Clin Cancer Res. 2005;11(23):8281-8287.
Discovered that a key DNA repair gene is turned off in half of all colon cancers and in surrounding non-cancerous colon cells as well, suggesting that the cancer occurred in a larger “field” of abnormal (but not yet malignant) colon cells.
Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, Houlihan PS, Krouse RS, Prasad AR, Einspahr JG, Buckmeier J, Alberts DS, Hamilton SR, Issa JP. MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst. 2005;97(18):1330-1338.
Issa JP. Epigenetic variation and human disease. J Nutr. 2002;132(8):2388S-2392S.
Demonstrated that specific precancerous (forerunner) genes are inactivated to stimulate early proliferation of premalignant cells in the development of bladder cancer.
Czerniak B, Li L, Chaturvedi V, Ro JY, Johnston DA, Hodges S, Benedict WF. Genetic modeling of human urinary bladder carcinogenesis. Genes Chromosomes Cancer. 2000;27(4):392-402.
Tuziak T, Jeong J, Majewski T, Kim MS, Steinberg J, Wang Z, Yoon DS, Kuang TC, Baggerly K, Johnston D, Czerniak B. High-resolution whole-organ mapping with SNPs and its significance to early events in carcinogenesis. Lab Invest. 2005;85(5):689-701.
Discovered the tumor suppressor gene PTEN and identified mutations that eliminate PTEN function.
Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997;15(4):356-362.
Discovered that UV-induced p53 mutations arise very early during skin cancer development and that inhibition of p53 mutations by sunscreens protects against skin cancer development.
Ananthaswamy HN, Ullrich SE, Mascotto RE, Fourtanier A, Loughlin SM, Khaskina P, Bucana CD, Kripke ML. Inhibition of solar simulator-induced p53 mutations and protection against skin cancer development in mice by sunscreens. J Invest Dermatol. 1999;112(5):763-768.
Ananthaswamy HN, Loughlin SM, Ullrich SE, Kripke ML. Inhibition of UV-induced p53 mutations by sunscreens: implications for skin cancer prevention. J Investig Dermatol Symp Proc. 1998;3(1):52-56.
Ananthaswamy HN, Loughlin SM, Cox P, Evans RL, Ullrich SE, and Kripke ML. Sunlight and skin cancer: Inhibition of p53 mutations in UV-irradiated mouse skin by sunscreens. Nature Med. 3:510-513, 1997.
First to identify Bcr as a tumor suppressor gene in the leukemic effects caused by the Bcr-Abl oncoprotein in chronic myeloid leukemia.
Lin F, Liu J, Monaco G, Sun T, Liu, Lin H, Stephens C, Belmont J, Arlinghaus RB. BCR gene expression blocks Bcr-Abl induced pathogenicity in a mouse model. Oncogene 20:1873-1881, 2001.
Hawk N, Sun T, Xie S, Wang Y, Wu Y, Liu J, Arlinghaus RB. Inhibition of the Bcr-Abl oncoprotein by Bcr requires phosphoserine 354. Cancer Research 62: 386-390, 2002.
Discovered the function of the p53 tumor suppressor gene as a transcriptional activator; demonstrated that common p53 mutations found in human cancers are transcriptionally inactive.
Raycroft L, Wu H and Lozano G. Transcriptional activation by wild-type but not transforming mutants of the p53 antioncogene. Science, 249:1049-1051, 1990.
Raycroft L, Schmidt JR, Yoas K, Hao M and Lozano G. Analysis of p53 mutants for transcriptional activity. Mol. Cell. Biol., 11:6067-6074, 1991.
Discovered the importance of dampening p53 function in normal tissues by two inhibitors Mdm2 and Mdm4. These inhibitors also suppress p53 activity in human cancers.
Montes de Oca Luna R, Wagner DS, and Lozano G. Rescue of early embryonic lethality in mdm-2 deficient mice by deletion of p53. Nature, 378:203-206, 1995.
Parant J, Chavez-Reyes A, Little NA, Yan W, Reinke V, Jochemsen AG and Lozano G. Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a non-overlapping pathway with MDM2 to regulate p53. Nature Genet., 29:92-95, 2001.
Discovered a new gene called “Dead End” that modifies testicular cancers in mice.
Youngren K, Coveney D, Peng X, Bhattacharya C, Schmidt LS, Nickerson ML, Lamb B, Deng JM, Behringer RR, Capel B, Rubin E, Nadeau J and Matin A. The Ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumours. Nature 435: 360-364, 2005.
Discovered the importance of two proteins, Pot1 and Pot2, in protecting the ends of the DNA (telomeres) from unraveling and becoming mutageneic.
Wu L, Multani AS, He H, Cosme-Blanco W, Deng Y, Deng JM, Bachilo O, Pathak S, Tahara H, Bailey SM, Deng Y, Behringer RR and Chang S. Pot1 Deficiency Initiates DNA Damage Checkpoint Activation and Aberrant Homologous Recombination at Telomeres. Cell 126:49-62, 2006.
He H, Multani AS, Cosme-Blanco W, Tahara H, Ma J, Pathak S, Deng Y, and Chang S. Pot2 Protects Telomeres From End-to-End Chromosomal Fusions and Aberrant Homologous Recombination. EMBO J, 25 (21): 5180-90, 2006.
Determined the mechanism by which TAp63, a molecule in the p53 family of genes, suppresses cancer metastasis. Showed that changes in TAp63 cause tumors to be more aggressive and act through microRNAs and another gene, Dicer.
Su X, Chakravarti D, Cho MS, Liu L, Gi YJ, Lin YL, Leung ML, El-Naggar A, Creighton CJ, Suraokar MB, Wistuba I, Flores ER. TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature 2010;467(7318):986-990.