BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

Tumours are known as wounds that do not heal - this implies that cells that are involved in angiogenesis and the response to injury, such as endothelial cells and fibroblasts, have a prominent role in the progression, growth and spread of cancers. Fibroblasts are associated with cancer cells at all stages of cancer progression, and their structural and functional contributions to this process are beginning to emerge. Their production of growth factors, chemokines and extracellular matrix facilitates the angiogenic recruitment of endothelial cells and pericytes. Fibroblasts are therefore a key determinant in the malignant progression of cancer and represent an important target for cancer therapies.

Fibroblasts in cancer

Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs

Purpose To improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression–based “intrinsic” subtypes luminal A, luminal B, HER2-enriched, and basal-like. Methods A 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and 133 patients were evaluated for prediction of pathologic complete response (pCR) to a taxane and anthracycline regimen. Results The intrinsic subtypes as discrete entities showed prognostic significance (P = 2.26E-12) and remained significant in multivariable analyses that incorporated standard parameters (estrogen receptor status, histologic grade, tumor size, and node status). A prognostic model for node-negative breast cancer was built using intrinsic subtype and clinical information. The C-index estimate for t...

/pdf/supervised-risk-predictor-of-breast-cancer-based-on-32oqdfzz8t.pdf

Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes

Cancer Metastasis: Building a Framework

The KEAP1/NRF2 pathway is a master regulator of the redox stress response and is dysregulated in numerous human tumors. We discovered that NRF2 signaling is controlled by the site-specific glycosylation of KEAP1, revealing a potentially broad link among nutrient sensing, proteostasis and stress resistance in both normal and cancer cells.

KEAP1 has a sweet spot: A new connection between intracellular glycosylation and redox stress signaling in cancer cells.

Purpose of Review
Human erythrocytes are responsible for oxygen delivery in the body. Erythrocytes are a product of terminal differentiated erythroid cells that accumulate hemoglobin and exclude nuclei. The long-held conventional wisdom has been that mature erythrocytes lack any genetic materials. Contrary to this view, accumulating evidence from multiple groups indicates that erythrocytes contain abundant and diverse RNA species. These newly discovered genetic materials suddenly open up opportunities to re-examine many diseases affecting erythrocytes.

Discovery, Genomic Analysis, and Functional Role of the Erythrocyte RNAs

Methods to determine the susceptibility of a subject to erythrocyte diseases are provided The methods comprise determining the miRNA compositions of erythrocytes from the subject The present invention has discovered that erythrocytes comprise microRNA (miRNA) populations and the populations can be profiled or analyzed and used to determine the susceptibility for disease The miRNA compositions can also be used to determine the severity of erythrocyte disease, and the features and clinical phenotypes of the erythrocyte disorders Also provided are pharmaceutical compositions comprising erythrocyte miRNAs and methods for the treatment of a subject with an erythrocyte disease In other embodiments of the invention, the miRNAs can be used to increase the life-span of erythrocytes through the introduction of an erythrocyte miRNA

Methods and compositions for the treatment of erythrocyte diseases

Nutrient deprivation triggers stringent response in bacteria, allowing rapid reallocation of resources from proliferation toward stress survival. Critical to this process is the accumulation/degradation of (p)ppGpp regulated by the RelA/SpoT homologues. While mammalian genomes encode MESH1, a homologue of the bacterial (p)ppGpp hydrolase SpoT, neither (p)ppGpp nor its synthetase has been identified in mammalian cells. Therefore, the function of MESH1 remains a mystery. Here, we report that human MESH1 is an efficient cytosolic NADPH phosphatase, an unexpected enzymatic activity that is captured by the crystal structure of the MESH1-NADPH complex. MESH1 depletion promotes cell survival under ferroptosis-inducing conditions by sustaining the level of NADPH, an effect that is reversed by the simultaneous depletion of the cytosolic NAD(H) kinase, NADK, but not its mitochondrial counterpart NADK2. Importantly, MESH1 depletion also triggers extensive transcriptional changes that are distinct from the canonical integrated stress response but resemble the bacterial stringent response, implicating MESH1 in a previously uncharacterized stress response in mammalian cells.

https://www.biorxiv.org/content/biorxiv/early/2018/05/17/325266.full.pdf

Mammalian stringent-like response mediated by the cytosolic NADPH phosphatase MESH1

Human red blood cells (RBCs), or erythrocytes, are the most abundant blood cells responsible for gas exchange. RBC diseases affect hundreds of millions of people and impose enormous financial and personal burdens. One well-recognized, but poorly understood feature of RBC populations within the same individual are their phenotypic heterogeneity. The granular characterization of phenotypic RBC variation in normative and disease states may allow us to identify the genetic determinants of red cell diseases and reveal novel therapeutic approaches for their treatment. Previously, we discovered diverse RNA transcripts in RBCs that has allowed us to dissect the phenotypic heterogeneity and malaria resistance of sickle red cells. However, these analyses failed to capture the heterogeneity found in RBC sub-populations. To overcome this limitation, we have performed single cell RNA-Seq to analyze the transcriptional heterogeneity of RBCs from three adult healthy donors which have been stored in the blood bank conditions and assayed at day 1 and day 15. The expression pattern clearly separated RBCs into seven distinct clusters that include one RBC cluster that expresses HBG2 and a small population of RBCs that express fetal hemoglobin (HbF) that we annotated as F cells. Almost all HBG2-expessing cells also express HBB, suggesting bi-allelic expression in single RBC from the HBG2/HBB loci, and we annotated another cluster as reticulocytes based on canonical gene expression. Additional RBC clusters were also annotated based on the enriched expression of NIX, ACVR2B and HEMGN, previously shown to be involved in erythropoiesis. Finally, we found the storage of RBC was associated with an increase in the ACVR2B and F-cell clusters. Collectively, these data indicate the power of single RBC RNA-Seq to capture and discover known and unexpected heterogeneity of RBC population.

/pdf/single-cell-rna-seq-analysis-of-human-red-cells-3jy2tsr5.pdf

Jen-Tsan Chi

Papers

KEAP1 has a sweet spot: A new connection between intracellular glycosylation and redox stress signaling in cancer cells.

Discovery, Genomic Analysis, and Functional Role of the Erythrocyte RNAs

Methods and compositions for the treatment of erythrocyte diseases

Mammalian stringent-like response mediated by the cytosolic NADPH phosphatase MESH1

Single Cell RNA-Seq Analysis of Human Red Cells