Tracing the geographic origins of weedy Ipomoea purpurea in the southeastern United States.

Ipomoea purpurea (common morning glory) is an annual vine native to Mexico that is well known for its large, showy flowers. Humans have spread morning glories worldwide, owing to the horticultural appeal of morning glory flowers. Ipomoea purpurea is an opportunistic colonizer of disturbed habitats including roadside and agricultural settings, and it is now regarded as a noxious weed in the Southeastern US.

Nucleotide sequence diversity of floral pigment genes in Mexican populations of Ipomoea purpurea (morning glory) accord with a neutral model of evolution.

The common morning glory (Ipomoea purpurea) is an annual vine native to Central and Southern Mexico. The genetics of flower color polymorphisms and interactions with the biotic environment have been extensively studied in I. purpurea and in its sister species I.

Targeting KRAS mutation-bearing lung cancer in vivo by pulmonary surfactant-adenovirus-mediated gene transfer.

Pulmonary surfactant has been used as a carrier to deliver a therapeutic virus to dysfunctional lung cells that reside within an intricate lung structure. To investigate whether pulmonary surfactant enhances the efficacy of intratracheal instillation of a therapeutic virus to target KRAS mutation-bearing lung cancer in vivo, we developed a recombinant adenovirus that induces cell death only in lung cancer cells and injected the adenovirus into a mouse model of KRAS mutation-positive lung cancer intratracheally with and without surfactant. A therapeutic adenovirus that induces cell death only in lung cancer cells was constructed by combining a cancer-specific human telomerase reverse transcriptase (hTERT) promoter fused to CCAAT/enhancer-binding protein alpha (CEBPα) with a modified lung-specific Clara cell-specific 10-kDa protein (CC10) promoter fused to cytotoxic adenovirus type 5 early region 1A (E1A).

Inhibition of Myc effectively targets KRAS mutation-positive lung cancer expressing high levels of Myc.

Myc is an oncogenic transcription factor that promotes tumorigenesis. Recently, a dominant negative form of Myc (Omomyc) was shown to cause regression of lung tumors in a mouse model of lung cancer caused by KRAS mutation, suggesting that Myc might be a potential therapeutic target to treat the KRAS lung cancer. However, it is not yet known whether Omomyc can also inhibit the growth of human lung tumors that carry a similar KRAS mutation.

Adenovirus-mediated cancer gene therapy and virotherapy (Review).

Gene therapy and virotherapy are among the approaches currently used to treat malignant tumors. Gene therapy and virotherapy use a specific therapeutic gene that causes death in cancer cells. In early attempts at gene therapy, therapeutic genes were driven by ubiquitous promoters such as the CMV promoter, which induce non-specific toxicity to normal cells and tissues in addition to the cancer cells.

Drug-regulatable cancer cell death induced by BID under control of the tissue-specific, lung cancer-targeted TTS promoter system.

Gene therapy and virotherapy are among the approaches currently being used to treat lung cancer. The success of cancer gene therapy depends on treatments where different types of tumors can be selectively targeted and destroyed without affecting normal cells and tissue. Previously, we described a promoter system (TTS) that we designed that is specifically targeted to lung cancer cells but which does not affect other types of cells including stem cells.

Malignant pleural mesothelioma-targeted CREBBP/EP300 inhibitory protein 1 promoter system for gene therapy and virotherapy.

Gene therapy and virotherapy are one of the approaches used to treat malignant pleural mesothelioma. To improve the efficiency of targeting malignant mesothelioma cells, we designed a novel system using the promoter of the CREBBP/EP300 inhibitory protein 1 (CRI1), a gene specifically expressed in malignant pleural mesothelioma. Four tandem repeats of the CRI1 promoter (CRI1(-138 4x)) caused significantly high promoter activity in malignant pleural mesothelioma cells but little promoter activity in normal mesothelial cells and normal fibroblasts.

Pulmonary adenocarcinoma-targeted gene therapy by a cancer- and tissue-specific promoter system.

Gene therapy is one of the approaches used to treat lung cancer. The benefit of cancer gene therapy is that different types of tumors can be selectively targeted by tumor-specific expression of therapeutic genes that include an apoptosis gene to destroy the tumor. Previously, we described a promoter (TTS promoter) that we designed that is specifically targeted to lung cancer cells but not to other types of cancer or normal cells including stem cells.

Development of a novel beta-cell specific promoter system for the identification of insulin-producing cells in in vitro cell cultures.

Recently, it has been reported that islet transplantation into patients with Type 1 diabetes may achieve insulin independence for a year or longer [Shapiro et al., Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen, N Engl J Med. 343 (2000) 230-238].

Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4alpha (HNF4alpha) gene.

The liver is exposed to a wide variety of toxic agents, many of which damage DNA and result in increased levels of the tumour suppressor protein p53. We have previously shown that p53 inhibits the transactivation function of HNF (hepatocyte nuclear factor) 4alpha1, a nuclear receptor known to be critical for early development and liver differentiation. In the present study we demonstrate that p53 also down-regulates expression of the human HNF4alpha gene via the proximal P1 promoter.

Genes that determine flower color: the role of regulatory changes in the evolution of phenotypic adaptations.

A central goal of evolutionary genetics is to trace the causal pathway between mutations at particular genes and adaptation at the phenotypic level. The proximate objective is to identify adaptations through the analysis of molecular sequence data from specific candidate genes or their regulatory elements. In this paper, we consider the molecular evolution of floral color in the morning glory genus (Ipomoea) as a model for relating molecular and phenotypic evolution.

Tracing floral adaptations from ecology to molecules.

Flowers have long fascinated humans. The scientific study of floral biology unifies many diverse areas of research, ranging from systematics to ecology, and from genetics to molecular biology. Despite this unity, few plant species offer the experimental versatility to encompass all levels of biological investigation in a single system.