Biochemistry, Biophysics, and Structural Biology Commons^™

The Role Of The Pleckstrin Homology Domain-Containing Protein Ckip-1 In Activation Of P21-Activated Kinase 1 (Pak1), Yong-Bae Kim, Yong Jae Shin, Adhiraj Roy, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Upon growth factor stimulation, PAK1 is recruited to the plasma membrane and activated by a mechanism that requires its phosphorylation at S223 by the protein kinase CK2. However, the upstream signaling molecules that regulate this phosphorylation event are not clearly defined. Here, we demonstrate a major role of the CK2α-interacting protein CKIP-1 in activation of PAK1. CK2α, CKIP-1 and PAK1 are translocated to membrane ruffles in response to the epidermal growth factor (EGF), where CKIP-1 mediates the interaction between CK2α, and PAK1 in a PI3K-dependent manner. Consistently, we observe that PAK1 mediates phosphorylation and modulation of the activity of p41-Arc, …

Topbp1 Governs Hematopoietic Stem/Progenitor Cells Survival In Zebrafish Definitive Hematopoiesis., Lei Gao, Dantong Li, Ke Ma, Wenjuan Zhang, Tao Xu, Wenge Zhu, +12 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

In vertebrate definitive hematopoiesis, nascent hematopoietic stem/progenitor cells (HSPCs) migrate to and reside in proliferative hematopoietic microenvironment for transitory expansion. In this process, well-established DNA damage response pathways are vital to resolve the replication stress, which is deleterious for genome stability and cell survival. However, the detailed mechanism on the response and repair of the replication stress-induced DNA damage during hematopoietic progenitor expansion remains elusive. Here we report that a novel zebrafish mutantcas003 with nonsense mutation in topbp1 gene encoding topoisomerase II β binding protein 1 (TopBP1) exhibits severe definitive hematopoiesis failure. Homozygous topbp1cas003 mutants manifest reduced number of HSPCs …

Generating A Focused View Of Disease Ontology Cancer Terms For Pan-Cancer Data Integration And Analysis., Tsung-Jung Wu, Lynn M. Schriml, Qing-Rong Chen, Maureen Colbert, Daniel J. Crichton, Raja Mazumder, Ying Hu, + 10 More

Biochemistry and Molecular Medicine Faculty Publications

Bio-ontologies provide terminologies for the scientific community to describe biomedical entities in a standardized manner. There are multiple initiatives that are developing biomedical terminologies for the purpose of providing better annotation, data integration and mining capabilities. Terminology resources devised for multiple purposes inherently diverge in content and structure. A major issue of biomedical data integration is the development of overlapping terms, ambiguous classifications and inconsistencies represented across databases and publications. The disease ontology (DO) was developed over the past decade to address data integration, standardization and annotation issues for human disease data. We have established a DO cancer project to …

Assessing Glucose Uptake Through The Yeast Hexose Transporter 1 (Hxt1), Adhiraj Roy, Angela D. Dement, Kyu Hong Cho, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

The transport of glucose across the plasma membrane is mediated by members of the glucose transporter family. In this study, we investigated glucose uptake through the yeast hexose transporter 1 (Hxt1) by measuring incorporation of 2-NBDG, a non-metabolizable, fluorescent glucose analog, into the yeast Saccharomyces cerevisiae. We find that 2-NBDG is not incorporated into the hxt null strain lacking all glucose transporter genes and that this defect is rescued by expression of wild type Hxt1, but not of Hxt1 with mutations at the putative glucose-binding residues, inferred from the alignment of yeast and human glucose transporter sequences. Similarly, the …

Cis-Encoded Non-Coding Antisense Rnas In Streptococci And Other Low Gc Gram (+) Bacterial Pathogens, Kyu Hong Cho, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Due to recent advances of bioinformatics and high throughput sequencing technology, discovery of regulatory non-coding RNAs in bacteria has been increased to a great extent. Based on this bandwagon, many studies searching for trans-acting small non-coding RNAs in streptococci have been performed intensively, especially in the important human pathogen, group A and B streptococci. However, studies for cis-encoded non-coding antisense RNAs in streptococci have been scarce. A recent study shows antisense RNAs are involved in virulence gene regulation in group B streptococcus, S. agalactiae. This suggests antisense RNAs could have important roles in the pathogenesis of streptococcal …

Is There Pandemic Vitamin D Deficiency In The Black Population? A Review Of Evidence, Ria S. Roberts, Fafa Huberta Koudoro, Mark S. Elliott, Zhiyong Han

Biochemistry and Molecular Medicine Faculty Publications

Although 1,25-dihydroxyvitamin D [1,25(OH)2D] is the biologically active form of vitamin D, measurement of the total serum 25-hydroxyvitamin D [25(OH)D] level is the gold standard used to define vitamin D status. Currently, it is widely accepted that serum 25 (OH) D levels below 20 ng/ml defines vitamin D deficiency. According to this definition, there appears to be pandemic vitamin D deficiency in the Black population. However, there is no evidence of higher-thannormal rates of common complications and symptomology of true vitamin D deficiency in the Black population. What is going on? We researched the MEDLINE databases to find studies, from …

The Global Cancer Genomics Consortium's Symposium: New Era Of Molecular Medicine And Epigenetic Cancer Medicine - Cross Section Of Genomics And Epigenetics, Masakazu Toi, M. Radhakrishna Pillai, Sudeep Gupta, Rajendra Badwe, Maria Carmo-Fonseca, Luis Costa, Loius W.C. Chow, Stefan Knapp, Rakesh Kumar

Biochemistry and Molecular Medicine Faculty Publications

The Global Cancer Genomics Consortium (GCGC) colleagues continue to function together as an interactive multidisciplinary team of cancer biologists and oncologists with interests in genomics and building a bidirectional bridge between cancer clinics and laboratories while taking advantage of shared resources among its member scientists. The GCGC includes member scientists from six institutions in Lisbon, United Kingdom, Japan, India and United States, and was formed in December 2010 for a period of five years. Driven by valuable lessons learned from the previous symposiums, the fourth GCGC Symposium focused on a cross section of genomic and epigenetic cancer medicine and it's …

Investigation Of Sex Differences In The Expression Of Rora And Its Transcriptional Targets In The Brain As A Potential Contributor To The Sex Bias In Autism, Valerie Wailin Hu, Tewarit Sarachana, Rachel M. Sherrard, Kristen M. Kocher

Biochemistry and Molecular Medicine Faculty Publications

Background

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by significant impairment in reciprocal social interactions and communication coupled with stereotyped, repetitive behaviors and restricted interests. Although genomic and functional studies are beginning to reveal some of the genetic complexity and underlying pathobiology of ASD, the consistently reported male bias of ASD remains an enigma. We have recently proposed that retinoic acid-related orphan receptor alpha (RORA), which is reduced in the brain and lymphoblastoid cell lines of multiple cohorts of individuals with ASD and oppositely regulated by male and female hormones, might contribute to the sex bias …

Anti-Inflammatory Effect Of 1,3,5,7-Tetrahydroxy-8-Isoprenylxanthone Isolated From Twigs Of Garcinia Esculenta On Stimulated Macrophage., Dan-Dan Zhang, Hong Zhang, Yuan-Zhi Lao, Rong Wu, Jin-Wen Xu, Ferid Murad, Ka Bian, Hong-Xi Xu

Biochemistry and Molecular Medicine Faculty Publications

Garcinia Linn. plants having rich natural xanthones and benzophenones with anti-inflammatory activity attracted a great deal of attention to discover and develop them as potential drug candidates. Through screening targeting nitric oxide accumulation in stimulated macrophage, we found that 1,3,5,7-tetrahydroxy-8-isoprenylxanthone (TIE) had potential anti-inflammatory effect. To understand how TIE elicits its anti-inflammatory activity, we uncovered that it significantly inhibits the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS/IFNγ-stimulated RAW264.7 cells. In further study, we showed that TIE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), two key molecules responsible for the production of …

Bioxpress: An Integrated Rna-Seq-Derived Gene Expression Database For Pan-Cancer Analysis., Quan Wan, Hayley Dingerdissen, Yu Fan, Naila Gulzar, Yang Pan, Tsung-Jung Wu, Cheng Yan, Haichen Zhang, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

BioXpress is a gene expression and cancer association database in which the expression levels are mapped to genes using RNA-seq data obtained from The Cancer Genome Atlas, International Cancer Genome Consortium, Expression Atlas and publications. The BioXpress database includes expression data from 64 cancer types, 6361 patients and 17 469 genes with 9513 of the genes displaying differential expression between tumor and normal samples. In addition to data directly retrieved from RNA-seq data repositories, manual biocuration of publications supplements the available cancer association annotations in the database. All cancer types are mapped to Disease Ontology terms to facilitate a uniform …

Targeting Metastatic Breast Cancer: Problems And Potential [Version 1; Referees: 5 Approved], Sarah Deasy, Karol Szczepanek, Kent Hunter

Biochemistry and Molecular Medicine Faculty Publications

Breast cancer is one of the leading causes of cancer-related mortality of women in the United States. Since the majority of cancer deaths are due to metastases rather than the primary tumor, a better understanding of the biological mechanisms that lead to metastatic disease is critical to reduce breast cancer associated mortality. Current adjuvant therapies use the same broadly cytotoxic and targeted strategies against metastases as are used against the primary tumor. However, resistance to chemotherapy due to the cellular dormancy, high genotypic and phenotypic heterogeneity between primary tumor and metastases as well as among individual metastases, and the limitations …

Advantages Of Distributed And Parallel Algorithms That Leverage Cloud Computing Platforms For Large-Scale Genome Assembly, Phil Kumari, Raja Mazumder, Vahan Simonyan, Konstantinos Krampis

Biochemistry and Molecular Medicine Faculty Publications

Background: The transition to Next Generation sequencing (NGS) sequencing technologies has had numerous applications in Plant, Microbial and Human genomics during the past decade. However, NGS sequencing trades high read throughput for shorter read length, increasing the difficulty for genome assembly. This research presents a comparison of traditional versus Cloud computing-based genome assembly software, using as examples the Velvet and Contrail assemblers and reads from the genome sequence of the zebrafish (Danio rerio) model organism.

Results: The first phase of the analysis involved a subset of the zebrafish data set (2X coverage) and best results were obtained using …

Hcv Infection-Associated Hepatocellular Carcinoma In Humanized Mice., Zhao Wang, Ningbin Wu, Abeba Tesfaye, Stephen Feinstone, Ajit Kumar

Biochemistry and Molecular Medicine Faculty Publications

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is a major risk factor for chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Our aim is to explore molecular changes that underlie HCV infection-associated HCC in a humanized mouse model, in order to identify markers of HCC progression.

METHODS: Liver proteins from human hepatocyte-engrafted and HCV-infected MUP-uPA/SCID/Bg mice were compared with either uninfected controls or HCV-infected but HCC-negative mice by Western blotting. MicroRNA markers of HCC positive or uninfected mouse liver were analyzed by RT-PCR.

RESULTS: We describe the depletion of tumor suppressor proteins and induction of oncoproteins and oncogenic microRNAs (oncomiRs) …

The Genus Cerion (Gastropoda: Cerionidae) In The Florida Keys., Yesha Shrestha, Herman H. Wirshing, M. G. Harasewych

Biochemistry and Molecular Medicine Faculty Publications

The systematic relationships and phylogeography of Cerion incanum, the only species of Cerion native to the Florida Keys, are reviewed based on partial sequences of the mitochondrial COI and 16S genes derived from 18 populations spanning the range of this species and including the type localities of all four described subspecies. Our samples included specimens of Cerion casablancae, a species introduced to Indian Key in 1912, and a population of C. incanum x C. casablancae hybrids descended from a population of C. casablancae introduced onto Bahia Honda Key in the same year. Molecular data did not support the partition of …