On becoming a cancer biologist

I am not a cancer biologist but I am becoming one. Becoming is a process, a transformation. Taking what was and using it as the foundation for what is or what will be

MicroRNAs, Cellular Behavior, and Endometrial Cancer

Endometrial cancer is the most common gynecological cancer and the fourth most common cancer in women worldwide. In spite of its’ relative importance to overall morbidity among women, molecular research in endometrial cancers lags far behind other cancers such as breast and colorectal. Nowhere is this more true than in research in the newly emergent field of post-transcriptional gene regulation by small, regulatory RNAs, primarily microRNAs (miRNAs). Here, structure, biogenesis, and mode of action of miRNAs is presented along with a brief overview of the role of miRNAs in carcinogenesis and a review of the few miRNA studies in endometrial cancer carried out to date

The Oncoplacental Gene Placenta-Specific Protein 1 Is Highly Expressed in Endometrial Tumors and Cell Lines

Placenta-specific protein 1 (PLAC1) is a small secreted protein expressed exclusively in trophoblast cells in the mammalian placenta. PLAC1 is expressed early in gestation and is maintained throughout. It is thought to function in trophoblast invasion of the uterine epithelium and, subsequently, to anchor the placenta to the epithelium. In recent years, evidence has accumulated that PLAC1 is also expressed in a variety of human solid tumors, notably in breast cancers. We demonstrate for the first time that PLAC1 is ubiquitously expressed in tumors originating in uterine epithelium. Further, we find that PLAC1 expression is significantly higher in the more advanced, more aggressive endometrial serous adenocarcinomas and carcinosarcomas relative to endometrioid adenocarcinomas by more than 6-fold and 16-fold, respectively. We also show that PLAC1 is simultaneously transcribed from two promoters but that, in all cases, the more distal P1 promoter dominates the more proximal P2 promoter. While the function of the two PLAC1 promoters and their regulation are as yet unknown, overall expression data suggest that PLAC1 may serve as a biomarker for endometrial cancer as well as a potential prognostic indicator

Division of Reproductive Science Research

The Division of Reproductive Science Research at the University of Iowa has a long tradition and was formally organized in 2009. Since then, the division has enjoyed extensive growth and development in many areas of reproductive research. Sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the NIH Office of Research on Women’s Health, a Women’s Reproductive Health Research Career Development Center, was established to train future physician-scientists. Further, to enhance our capability to perform translational research, the Women’s Health Tissue Repository was established. This robust bio-repository includes the Maternal Fetal Tissue Bank, the Paternal Contributions to Children’s Health Biobank, the Well Woman Bank, the Reproductive Endocrinology and Infertility Biobank, and the Gynecologic Malignancies Biobank. Together, these biobanks collect samples from all stages of women’s lives and have deep clinical annotations

Toward a microRNA signature of endometrial cancer

A simple meta-analysis of eight microRNA (miRNA) expression surveys of endometrial cancers reveals a panel of sixteen miRNAs that are significantly over-expressed (n = 15) or under-expressed (n = 1) in at least three surveys. Examination of these miRNAs indicates that they target mRNAs involved in a number of basic cellular processes including the crucial epithelial to mesenchymal transition (EMT) and hypoxia response. The central role played by these miRNAs is reinforced by the demonstration that they are all among the most ancient of all animal miRNAs. This suggests that they are members of a core set of miRNAs dysregulated as part of the carcinogenic cellular reprogramming process

Neuromuscular Performance in a Kansas Mennonite Community: Age and Sex Effects in Performance

This is the published version. Copyright 1985 Wayne State University Press.The effects of age and sex on six neuromuscular performance traits are studied in a cross-sectional sample of 559 members of the Goessel, Kansas Mennonite community. Age and sex effects are assessed by stepwise polynomial regression which includes non-linear age terms up to the fourth power. Of the six traits studied only one, Hand Steadiness, fails to show a significant sex difference and only one, Trunk Flexibility, fails to show a significant non-linear trend with age. A general pattern, seen in these traits of accelerating performance decline after age 45 of up to 60%, is found to be consistent with that reported in other studies of the same traits. The consistency of this non-linear aging pattern suggests the presence of a general neuromuscular aging process. Moreover, this process appears likely to be related to a two-stage mechanism inferred from both animal and human studies involving a decline in protein synthesis and a loss of cell mass in nerve and muscle tissue

Preeclampsia and MicroRNAs

Preeclampsia is a critical gestational condition that threatens the life of both mother and child. One of the most serious aspects of preeclampsia hampering both clinical management and scientific understanding is that there are, as yet, no early warning signs or risk markers. The discovery of microRNAs (miRNAs), tiny post-transcriptional regulators of gene expression, offers potentially fertile ground for developing such markers. The current state of knowledge about miRNAs in preeclampsia is presented along with information regarding miRNA detection in peripheral fluids that could lead to minimally invasive risk assessment

MiR-888: A newly identified miRNA significantly over-expressed in endometrial cancers

Endometrial cancer is the most common gynecological malignancy and the fourth most common cancer in women. With accumulating evidence, microRNAs have emerged as significant players in the development and progression of cancers. The data points to miR-888 playing an important functional role in the development of aggressive endometrial tumors. Future research will focus on identifying and validating the targets of miR-888 to elucidate its mechanism of action and support this hypothesi

Methodologies for In Vitro Cloning of Small RNAs and Application for Plant Genome(s)

The “RNA revolution” that started at the end of the 20th century with the discovery of post-transcriptional gene silencing and its mechanism via RNA interference (RNAi) placed tiny 21-24 nucleotide long noncoding RNAs (ncRNAs) in the forefront of biology as one of the most important regulatory elements in a host of physiologic processes. The discovery of new classes of ncRNAs including endogenous small interfering RNAs, microRNAs, and PIWI-interacting RNAs is a hallmark in the understanding of RNA-dependent gene regulation. New generation high-throughput sequencing technologies further accelerated the studies of this “tiny world” and provided their global characterization and validation in many biological systems with sequenced genomes. Nevertheless, for the many “yet-unsequenced” plant genomes, the discovery of small RNA world requires in vitro cloning from purified cellular RNAs. Thus, reproducible methods for in vitro small RNA cloning are of paramount importance and will remain so into the foreseeable future. In this paper, we present a description of existing small RNA cloning methods as well as next-generation sequencing methods that have accelerated this research along with a description of the application of one in vitro cloning method in an initial small RNA survey in the “still unsequenced” allotetraploid cotton genome