A Kinome-Wide Crispr Screen Identifies Ck1Α As A Target To Overcome Enzalutamide Resistance Of Prostate Cancer,
2023
University of Kentucky
A Kinome-Wide Crispr Screen Identifies Ck1Α As A Target To Overcome Enzalutamide Resistance Of Prostate Cancer, Jinghui Liu, Yue Zhao, Daheng He, Katelyn M. Jones, Shan Tang, Derek B. Allison, Yanquan Zhang, Jing Chen, Qiongsi Zhang, Xinyi Wang, Chaohao Li, Chi Wang, Lang Li, Xiaoqi Liu
Markey Cancer Center Faculty Publications
Enzalutamide (ENZA), a second-generation androgen receptor antagonist, has significantly increased progression-free and overall survival of patients with metastatic prostate cancer (PCa). However, resistance remains a prominent obstacle in treatment. Utilizing a kinome-wide CRISPR-Cas9 knockout screen, we identified casein kinase 1a (CK1a) as a therapeutic target to overcome ENZA resistance. Depletion or pharmacologic inhibition of CK1a enhanced ENZA efficacy in ENZA-resistant cells and patient-derived xenografts. Mechanistically, CK1a phosphorylates the serine residue S1270 and modulates the protein abundance of ataxia telangiectasia mutated (ATM), a primary initiator of DNA double-strand break (DSB)-response signaling, which is compromised in ENZA-resistant cells and patients. Inhibition of …
Identification Of A Nacc1-Regulated Gene Signature Implicated In The Features Of Triple-Negative Breast Cancer,
2023
University of Kentucky
Identification Of A Nacc1-Regulated Gene Signature Implicated In The Features Of Triple-Negative Breast Cancer, Chrispus Ngule, Hami Hemati, Xingcong Ren, Oluwafunminiyi Obaleye, Amos O. Akinyemi, Felix Oyelami, Xiaofang Xiong, Jianxun Song, Xia Liu, Jin-Ming Yang
Markey Cancer Center Faculty Publications
Triple-negative breast cancer (TNBC), characterized by a deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotypes such as tumor heterogeneity and therapy resistance, remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approaches, we found 55 up- and 9 downregulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration was positively correlated …
Leukocyte Tyrosine Kinase (Ltk) Is The Mendelian Determinant Of The Axolotl Melanoid Color Variant,
2023
University of Kentucky
Leukocyte Tyrosine Kinase (Ltk) Is The Mendelian Determinant Of The Axolotl Melanoid Color Variant, Mirindi Kabangu, Raissa Cecil, Lloyd Strohl Ii, Nataliya Y. Timoshevskaya, Jeramiah James Smith, Stephen Randal Voss
Markey Cancer Center Faculty Publications
The great diversity of color patterns observed among amphibians is largely explained by the differentiation of relatively few pigment cell types during development. Mexican axolotls present a variety of color phenotypes that span the continuum from leucistic to highly melanistic. The melanoid axolotl is a Mendelian variant characterized by large numbers of melanophores, proportionally fewer xanthophores, and no iridophores. Early studies of melanoid were influential in developing the single-origin hypothesis of pigment cell development, wherein it has been proposed that all three pigment cell types derive from a common progenitor cell, with pigment metabolites playing potential roles in directing the …
In Situ Microwave Fixation Provides An Instantaneous Snapshot Of The Brain Metabolome,
2023
University of Kentucky
In Situ Microwave Fixation Provides An Instantaneous Snapshot Of The Brain Metabolome, Jelena A. Juras, Madison B. Webb, Lyndsay E. A. Young, Kia H. Markussen, Tara R. Hawkinson, Michael D. Buoncristiani, Kayli E. Bolton, Peyton T. Coburn, Meredith I. Williams, Lisa P. Y. Sun, William C. Sanders, Ronald C. Bruntz, Lindsey R. Conroy, Chi Wang, Matthew S. Gentry, Bret N. Smith, Ramon C. Sun
Markey Cancer Center Faculty Publications
Brain glucose metabolism is highly heterogeneous among brain regions and continues postmortem. In particular, we demonstrate exhaustion of glycogen and glucose and an increase in lactate production during conventional rapid brain resection and preservation by liquid nitrogen. In contrast, we show that these post- mortem changes are not observed with simultaneous animal sacrifice and in situ fixation with focused, high- power microwave. We further employ microwave fixation to define brain glucose metabolism in the mouse model of streptozotocin-induced type 1 diabetes. Using both total pool and isotope tracing analyses, we identified global glucose hypometabolism in multiple brain regions, evidenced by …
Targeting Lncrna Ddit4-As1 Sensitizes Triple Negative Breast Cancer To Chemotherapy Via Suppressing Of Autophagy,
2023
Central South University; Hunan Provincial Engineering Research Centre of Translational Medicine and Innovative Drug
Targeting Lncrna Ddit4-As1 Sensitizes Triple Negative Breast Cancer To Chemotherapy Via Suppressing Of Autophagy, Ting Jiang, Jiaojiao Zhu, Shilong Jiang, Zonglin Chen, Ping Xu, Rong Gong, Changxin Zhong, Yueying Cheng, Xinyuan Sun, Wenjun Yi, Jinming Yang, Wenhu Zhou, Yan Cheng
Markey Cancer Center Faculty Publications
In this study, it is found that the lncRNA, DNA damage inducible transcript 4 antisense RNA1 (DDIT4-AS1), is highly expressed in triple-negative breast cancer (TNBC) cell lines and tissues due to H3K27 acetylation in the promoter region, and promotes the proliferation, migration, and invasion of TNBC cells via activating autophagy. Mechanistically, it is shown that DDIT4-AS1 induces autophagy by stabilizing DDIT4 mRNA via recruiting the RNA binding protein AUF1 and promoting the interaction between DDIT4 mRNA and AUF1, thereby inhibiting mTOR signaling pathway. Furthermore, silencing of DDIT4-AS1 enhances the sensitivity of TNBC cells to chemotherapeutic agents such as paclitaxel both …
Protocol To Identify The Core Gene Supported By An Essential Gene In E. Coli Bacteria Using A Genome-Wide Suppressor Screen,
2023
Thomas Jefferson University
Protocol To Identify The Core Gene Supported By An Essential Gene In E. Coli Bacteria Using A Genome-Wide Suppressor Screen, Isao Masuda, Ya-Ming Hou
Department of Biochemistry and Molecular Biology Faculty Papers
We describe here a genome-wide screening approach to identify the most critical core reaction among a network of many that are supported by an essential gene to establish cell viability. We describe steps for maintenance plasmid construction, knockout cell construction, and phenotype validation. We then detail isolation of suppressors, whole-genome sequencing analysis, and reconstruction of CRISPR mutants. We focus on E. coli trmD, which encodes an essential methyl transferase that synthesizes m1G37 on the 3'-side of the tRNA anticodon. For complete details on the use and execution of this protocol, please refer to Masuda et al. (2022).
Surveillance And Stewardship: Where Infection Prevention And Antimicrobial Stewardship Intersect,
2023
Cepheid
Surveillance And Stewardship: Where Infection Prevention And Antimicrobial Stewardship Intersect, Fred C. Tenover, Debra A. Goff
Biology Faculty Publications
Colonization with multidrug-resistant organisms (MDROs) is a risk factor for subsequent infection. Surveillance for MDROs, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Enterobacterales, and carbapenemase-producing organisms, is commonly conducted in hospitals to prevent spread of MDROs, in part to reduce the potential for additional infections. Although colonization is a risk factor for infection, data on colonization with various MDROs are often not considered when selecting anti-infective therapy. There are conflicting data on the strength of the positive and negative predictive values of the colonization test results to guide therapeutic strategies. Defining therapeutic strategies for patients with complicated or …
Rare Variant Enrichment Analysis Supports Greb1l As A Contributory Driver Gene In The Etiology Of Mayer-Rokitansky-Küster-Hauser Syndrome,
2023
The Texas Medical Center Library
Rare Variant Enrichment Analysis Supports Greb1l As A Contributory Driver Gene In The Etiology Of Mayer-Rokitansky-Küster-Hauser Syndrome, Angad Jolly, Haowei Du, Christelle Borel, Na Chen, Sen Zhao, Christopher M Grochowski, Ruizhi Duan, Jawid M Fatih, Moez Dawood, Sejal Salvi, Shalini N Jhangiani, Donna M Muzny, André Koch, Konstantinos Rouskas, Stavros Glentis, Efthymios Deligeoroglou, Flora Bacopoulou, Carol A Wise, Jennifer E Dietrich, Ignatia B Van Den Veyver, Antigone S Dimas, Sara Brucker, V Reid Sutton, Richard A Gibbs, Stylianos E Antonarakis, Nan Wu, Zeynep H Coban-Akdemir, Lan Zhu, Jennifer E Posey, James R Lupski
Faculty, Staff and Student Publications
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only WNT4 (MIM: 603490) variants have been definitively associated with a subtype of MRKH with hyperandrogenism (MIM: 158330). DNA from 148 clinically diagnosed MRKH probands across 144 unrelated families and available family members from North America, Europe, and South America were exome sequenced (ES) and by family-based genomics analyzed for rare likely deleterious variants. A replication cohort consisting of 442 Han Chinese individuals with MRKH was …
Margalefidinium Polykrikoides Cyst Resuspension In The Lafayette River, A Sub-Tributary Of The Chesapeake Bay,
2023
Old Dominion University
Margalefidinium Polykrikoides Cyst Resuspension In The Lafayette River, A Sub-Tributary Of The Chesapeake Bay, Gabrielle Greaney, Eduardo Perez Vega, Katherine Crider, Dreux Chappell, Kimberly Powell, Richard Hale, Peter Bernhardt, Margaret Mulholland
Undergraduate Research Symposium
Harmful Algal Blooms are a collection of algae in a body of water that can cause serious environmental issues and health problems in both people and aquatic organisms. Dinoflagellates are microscopic, unicellular, and eukaryotic organisms that are well known for forming harmful algal blooms because of eutrophication. Coastal Virginia suffers from HABs in the Chesapeake Bay and its tributaries. A common species of dinoflagellate, known as Margalefidinium polykrikoides exists in the Chesapeake Bay. The purpose of this study is to determine if sediment resuspension produced by wind generated surface gravity waves cause cysts (dinoflagellate resting stages) to be suspended into …
Functional Analysis Provides Insight Into Missing Heritability,
2023
WSU SOM Class of 2024
Functional Analysis Provides Insight Into Missing Heritability, Scott L. Baughan, Michael A. Tainsky, Fatima Darwiche
Medical Student Research Symposium
Accurate ascertainment of genetic risk can be potentially lifesaving for patients who inherit cancer promoting mutations. However, even with the most extensive panel testing clinically available, a large number of patients will test negative despite family history of cancer or test positive for a variant of unknown significance (VUS). For these patients, clinical management is complicated; patients want to know their risk, and may fear disease they are not at great risk for (benign VUS) or they may not be given access to potentially lifesaving early screening procedures (pathogenic VUS). ATM has proven a challenge to clinicians due to its …
Identifying Barriers And Facilitators To Family Communication Regarding Genetic Testing For Hereditary Cancer,
2023
University of South Florida
Identifying Barriers And Facilitators To Family Communication Regarding Genetic Testing For Hereditary Cancer, Andrea K. Shields
USF Tampa Graduate Theses and Dissertations
Cascade testing, whereby at-risk family members are tested for known pathogenic or likely pathogenic (P/LP) variants in high risk cancer genes, provides the opportunity for changes in medical management (e.g., increased surveillance to detect cancer early or preventative surgery to reduce cancer risk). However, the rates of cascade testing are low which suggests that one-time communication may be insufficient to prompt action among family, and an increase in understanding of how to promote ongoing communication about genetic testing within families is needed. We surveyed individuals with P/LP variants in inherited cancer genes and conducted multiple linear regression with forward analysis …
Needs Assessment For A Web-Based Support Resource For Patients With A Pathogenic Variant In Lmna,
2023
University of South Florida
Needs Assessment For A Web-Based Support Resource For Patients With A Pathogenic Variant In Lmna, Dylan M. Allen
USF Tampa Graduate Theses and Dissertations
Pathogenic variants (PV) in the gene LMNA cause autosomal dominant inherited “laminopathies” that can affect multiple different organs, most specifically the heart. Current resources for LMNA patients are sparse and disjointed, leaving a need for a comprehensive resource catering to the wants and needs of the patients. A needs assessment of LMNA support resources was completed through reviewing published literature and existing support resources and conducting 11 semi-structured interviews with individuals who have a PV in LMNA. The Social Support Theoretical Model and thematic analysis of interview transcripts were used to identify discrepancies between the support that affected individuals receive …
Using The Genetic Counseling Skills Checklist To Characterize Prenatal Genetic Counseling,
2023
University of South Florida
Using The Genetic Counseling Skills Checklist To Characterize Prenatal Genetic Counseling, David A. Cline
USF Tampa Graduate Theses and Dissertations
Genetic Counseling relies on communication skills to help patients understand and adapt to a genetic disease or risk. However, little is known about which skills are most commonly used or the extent to which genetic counseling sessions vary. A novel process measure titled the "Genetic Counseling Skills Checklist" (GCSC) was developed in a prior pilot study and includes 8 broad categories each consisting of 5-8 skills. This study is the first to apply the final GCSC to characterize 20 mock prenatal sessions conducted by 5 genetic counselors (GCs) for 2 prenatal indications using 3 trained actors as patients. Two experienced …
Healthcare Decision Makers' Perspectives On Barriers And Facilitators To Hiring Genetic Counselors In Huntington Disease (Hd) Clinic Settings,
2023
University of South Florida
Healthcare Decision Makers' Perspectives On Barriers And Facilitators To Hiring Genetic Counselors In Huntington Disease (Hd) Clinic Settings, Bailey Hummel
USF Tampa Graduate Theses and Dissertations
Huntington disease (HD) is a hereditary, neurodegenerative autosomal dominant disorder for which there are currently no effective options to prevent the onset of symptoms. Although meeting with a genetic counselor (GC) is recommended as part of national guidelines for predictive HD genetic testing and a GC is required for Centers of Excellence, not all HD centers have hired a GC. To explore drivers for, valued outcomes of, and barriers to the creation of GC positions in clinics that treat patients with HD, we conducted semi-structured interviews with 11 individuals involved with HD clinics and/or hiring decisions at 8 clinics across …
Piloting A Spanish-Language Web-Based Tool For Hereditary Cancer Genetic Testing,
2023
University of South Florida
Piloting A Spanish-Language Web-Based Tool For Hereditary Cancer Genetic Testing, Gretter Manso
USF Tampa Graduate Theses and Dissertations
Cancer genetic services (including genetic counseling and testing) help identify patients and families at increased risk of developing cancer so that steps can be taken to reduce risks or find cancers early. Receipt of genetic services in the Hispanic/Latinx population is low due, in part, to a shortage of Spanish-speaking genetic counselors. To address this concern, a 12-minute online tool designed to inform individuals about cancer genetic services was translated into Spanish. The objectives of this pilot study were to determine if the educational tool improves knowledge and informed decision making and to assess usability and appropriateness of the tool …
Evaluation Of A Story-Telling Approach To Educate Minority Populations About Inherited Cancer,
2023
University of South Florida
Evaluation Of A Story-Telling Approach To Educate Minority Populations About Inherited Cancer, Celestyn B. Angot
USF Tampa Graduate Theses and Dissertations
Utilization of hereditary cancer genetic counseling and testing services is substantially lower among minority populations compared to white populations due, in part, to lower levels of awareness and knowledge. To help improve awareness, we designed a 7-minute video that uses storytelling to translate knowledge of genetic testing and hereditary cancer to individuals who have a personal history or family history of cancer. Consented participants were asked baseline questions about hereditary cancer and genetic testing, reviewed the video, and provided feedback on its content, understandability, and visual appeal during semi-structured interviews. Data were coded and analyzed to identify themes and determine …
Theoretical Framework For The Study Of Genetic Diseases Caused By Dominant Alleles,
2023
Linfield University
Theoretical Framework For The Study Of Genetic Diseases Caused By Dominant Alleles, Michael Roberts, Stephen Bricher
Articles, Essays, & Creative Writing
We propose a theoretical basis for analyzing several features of genetic diseases caused by dominant alleles, including: disease prevalence, genotype penetrance, and the relationship between causal genotype frequency and disease frequency. In addition, we provide a theoretical framework for accurate diagnosis and clinical approaches for disease study, including two examples in which inaccurate and incomplete diagnoses affect the estimates of disease prevalence: First, the disease iceberg effect shows that disease prevalence is often underestimated due to errors introduced by inaccurate diagnosis; second, because lifetime risk of disease is cumulative, and therefore an increasing function of age, measurements of prevalence are …
Identifying Non-Traditional Slippery Sequences Associated With Translational Frameshifts,
2023
Purdue University
Identifying Non-Traditional Slippery Sequences Associated With Translational Frameshifts, Aaron J. Gin, Kari Lynn Clase
Graduate Industrial Research Symposium
Genetic frameshifts are a mutation in which
a nucleotide skip leads to a shift in the
reading frame. In viruses, these frameshifts
can be programmed using a slippery
sequence to bypass the stop codon
associated with the initial protein. This
allows for variable control of protein
expression. In bacteriophages, translational
frameshifts have been identified but only a
few have been proven experimentally. Using
experimental data and comparative
genomics, non-traditional slippery
sequences can be identified as assisting in
controlling the protein coding throughout
viruses. Novel slippery sequences can aid in
the understanding of protein expression in
biological environments and further the …
A Single-Cell Gene Expression Atlas Of Human Follicular Aspirates: Identification Of Leukocyte Subpopulations And Their Paracrine Factors,
2023
University of Kentucky
A Single-Cell Gene Expression Atlas Of Human Follicular Aspirates: Identification Of Leukocyte Subpopulations And Their Paracrine Factors, Yohan Choi, Hayce Jeon, Mats Brännström, James W. Akin, Thomas E. Curry, Misung Jo
UK CARES Faculty Publications
Leukocytes are in situ regulators critical for ovarian function. However, little is known about leukocyte subpopulations and their interaction with follicular cells in ovulatory follicles, especially in humans. Single-cell RNA sequencing (scRNA- seq) was performed using follicular aspirates obtained from four IVF patients and identified 13 cell groups: one granulosa cell group, one thecal cell group, 10 subsets of leukocytes, and one group of RBC/platelet. RNA velocity analyses on five granulosa cell populations predicted developmental dynamics denoting two projections of differentiation states. The cell type-specific transcriptomic profiling analyses revealed the presence of a diverse array of leukocyte-derived factors that can …
Impact Of The Dimethyl Sulfoxide Reductase Superfamily On The Evolution Of Biogeochemical Cycles,
2023
Colorado State University - Fort Collins
Impact Of The Dimethyl Sulfoxide Reductase Superfamily On The Evolution Of Biogeochemical Cycles, Michael Wells, Minjae Kim, Denise M. Akob, Partha Basu, John F. Stolz
UK CARES Faculty Publications
The dimethyl sulfoxide reductase (or MopB) family is a diverse assemblage of enzymes found throughout Bacteria and Archaea. Many of these enzymes are believed to have been present in the last universal common ancestor (LUCA) of all cellular lineages. However, gaps in knowledge remain about how MopB enzymes evolved and how this diversification of functions impacted global biogeochemical cycles through geologic time. In this study, we perform maximum likelihood phylogenetic analyses on manually curated comparative genomic and metagenomic data sets containing over 47,000 distinct MopB homologs. We demonstrate that these enzymes constitute a catalytically and mechanistically diverse superfamily defined not …
