Review
Biochemistry & Molecular Biology
Sarah S. Wang, Jihao Xu, Keely Y. Ji, Chang-Il Hwang
Summary: Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDA), is a significant cause of cancer-related deaths in the United States. While genetic mutations driving PDA initiation and progression have been identified, the mechanisms underlying PDA metastasis remain elusive. It is suggested that epigenetic fluctuations may play a critical role in driving PDA metastasis.
Review
Biochemistry & Molecular Biology
Eshaan Patnaik, Chikezie Madu, Yi Lu
Summary: Epigenetics plays a crucial role in gene regulation and tumor development. DNA methylation inhibitors and histone deacetylase inhibitors can restore normal gene expression and be effective against cancer. Understanding epigenetic modifications and utilizing inhibitors offer new possibilities for cancer research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Erolcan Sayar, Radhika A. Patel, Ilsa M. Coleman, Martine P. Roudier, Ailin Zhang, Pallabi Mustafi, Jin-Yih Low, Brian Hanratty, Lisa S. Ang, Vipul Bhatia, Mohamed Adil, Hasim Bakbak, David A. Quigley, Michael T. Schweizer, Jessica E. Hawley, Lori Kollath, Lawrence D. True, Felix Y. Feng, Neil H. Bander, Eva Corey, John K. Lee, Colm Morrissey, Roman Gulati, Peter S. Nelson, Michael C. Haffner
Summary: Prostate-specific membrane antigen (PSMA) expression is heterogeneous in metastatic castration-resistant prostate cancer (mCRPC), with some cases showing no detectable PSMA and others showing heterogeneous expression across metastases. Loss of PSMA is associated with epigenetic changes, including CpG methylation and loss of H3K27 acetylation at the FOLH1 locus. Treatment with HDAC inhibitors can reverse this repression and restore PSMA expression. These findings provide insights into PSMA expression patterns and regulation in mCRPC, and suggest a potential therapeutic strategy using epigenetic therapies to augment PSMA levels.
Article
Multidisciplinary Sciences
Daniel F. Clark, Rachael Schmelz, Nicole Rogers, Nuri E. Smith, Kimberly R. Shorter
Summary: The study found that excess folic acid can impact gene expression, epigenetic marks, and neuromorphology even when MTHFR is functioning normally. Folic acid treatment led to changes in gene expression of epigenetic modifying enzymes, alterations in global DNA methylation and hydroxymethylated DNA. Additionally, folic acid affected dendritic spine densities and histone modifications.
Article
Clinical Neurology
Qin Ma, Jorge R. Oksenberg, Alessandro Didonna
Summary: This study found that ATXN1 undergoes hypo-methylation at four distinct regions exclusively in B cells of multiple sclerosis patients, and these differentially methylated sites overlap with other regulatory epigenetic marks and MS risk variants. Luciferase assays showed that the loss of methylation leads to an increase in ATXN1 expression. The findings provide insights into ataxin-1 regulation in the immune system and the molecular mechanisms underlying MS risk.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Oncology
Samrat Roy Choudhury, Cody Ashby, Fenghuang Zhan, Frits van Rhee
Summary: Aberrant expression of telomere-related genes (TRGs) and telomere-shortening contribute to the development of different types of cancer, including high-risk multiple myeloma (MM) patients with critically shortened telomeres. The epigenetic network of aberrant gene expression in TRGs is shown to be regulated by DNA methylation in cooperation with chromatin marks and genomic sequences. DNA methylation at selective TRGs was found to correlate with gene expression, suggesting potential early detection biomarkers or therapeutic targets in MM patients.
Article
Medicine, General & Internal
Roberta Romano, Francesca Cillo, Cristina Moracas, Laura Pignata, Chiara Nannola, Elisabetta Toriello, Antonio De Rosa, Emilia Cirillo, Emma Coppola, Giuliana Giardino, Nicola Brunetti-Pierri, Andrea Riccio, Claudio Pignata
Summary: The epigenome plays a crucial role in fine-tuning gene transcription by bridging environmental factors and the genome. It involves various intricate changes, such as DNA methylation, chromatin remodeling, histone modifications, and RNA processing, which regulate physiological processes in development, maturation, and maintenance of cellular identity and function. Recent studies on genome-wide DNA methylation data have shed new light on the potential contribution of epigenetics in the pathophysiology of the immune system and host defense. Understanding environment-genome interactions through the study of patients with mutations in genes encoding for epigenetic machinery has provided insights and potential therapeutic options.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Oncology
Wesley N. Saintilnord, Yvonne Fondufe-Mittendorf
Summary: Arsenic, a ubiquitous metalloid, poses major health concerns worldwide due to its high toxicity, potentially driving oncogenic gene expression through mechanisms such as generation of reactive oxygen species or epigenetic dysregulation. Further research is needed to fully understand the role of arsenic in cancer development.
SEMINARS IN CANCER BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jorge Valencia-Ortega, Renata Saucedo, Martha A. Sanchez-Rodriguez, Jose G. Cruz-Duran, Edgar G. Ramos Martinez
Summary: Gestational diabetes mellitus is the most common metabolic complication in pregnancy, involving various factors in its pathophysiology. Studies have observed that alterations in DNA methylation patterns and certain microRNA levels are related to the disease characteristics, highlighting the need for further research in this area.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Melanie Blanc, Philipp Antczak, Xavier Cousin, Christoph Grunau, Nikolai Scherbak, Joelle Ruegg, Steffen H. Keiter
Summary: The study revealed transgenerational neurotoxic effects of permethrin in zebrafish, with possible underlying mechanisms related to stable dysregulation of glutamatergic signaling.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Biochemistry & Molecular Biology
Sadaf Harandi-Zadeh, Cayla Boycott, Megan Beetch, Tony Yang, Benjamin J. E. Martin, Kevin Ren, Anna Kwasniak, John H. Dupuis, Katarzyna Lubecka, Rickey Y. Yada, LeAnn J. Howe, Barbara Stefanska
Summary: Epigenetic aberrations are associated with sporadic breast cancer, and dietary polyphenols such as pterostilbene have been shown to regulate gene expression by altering epigenetic patterns. The study reveals an impact of pterostilbene on enhancer regions in breast cancer cells, affecting DNMT3B binding, H3K36me3 levels, enhancer hypermethylation, and gene expression downregulation. Additionally, the research highlights the involvement of oncogenic transcription factor OCT1 in mediating the effects of pterostilbene on enhancers and gene expression in breast cancer cells.
Article
Endocrinology & Metabolism
Fouzieh Salimi, Gholamreza Asadikaram, Mohammad Reza Ashrafi, Hamid Zeynali Nejad, Moslem Abolhassani, Mojtaba Abbasi-Jorjandi, Mojgan Sanjari
Summary: The purpose of this study was to investigate the impact of organochlorine pesticides (OCPs) on the promoter methylation of tumor-suppressor genes and histone modifications in thyroid nodules. The results showed that Papillary thyroid carcinoma (PTC) patients had higher TSHR methylation and lower P16 methylation compared to benign thyroid nodule (BTN) patients. OCPs increased the methylation of TSHR and P16, and decreased the acetylation of H3K9, H4K16, and H3K18 in PTC patients. Conclusion: OCPs contribute to PTC progression by promoting TSHR hypermethylation and decreasing H3K9 and H4K16 acetylation. Assessing TSHR methylation and H3K9, H4K16 acetylation could be predictive in PTC patients.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Review
Oncology
Liliana Montella, Mariella Cuomo, Nunzio Del Gaudio, Michela Buonaiuto, Davide Costabile, Roberta Visconti, Teodolinda Di Risi, Roberta Vinciguerra, Federica Trio, Sara Ferraro, Guglielmo Bove, Gaetano Facchini, Lucia Altucci, Lorenzo Chiariotti, Rosa Della Monica
Summary: This article reviews the druggable epigenetic features of glioblastomas and discusses the corresponding targeted therapies and their potential efficacy. It emphasizes the recent technological improvements that allow routine investigation of many glioblastoma epigenetic biomarkers in clinical practice.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Dentistry, Oral Surgery & Medicine
Andrea Gabusi, Davide B. Gissi, Sara Grillini, Martina Stefanini, Achille Tarsitano, Claudio Marchetti, Maria Pia Foschini, Lucio Montebugnoli, Luca Morandi
Summary: Preliminary data showed shared epigenetic alterations between PD and OSCC patients in two inflammatory genes (GP1BB and MIR193), indicating potential links between the two diseases. This study may provide insights for future research focused on the pathogenesis of PD and OSCC.
Review
Infectious Diseases
Jibran Sualeh Muhammad, Naveed Ahmed Khan, Sutherland K. Maciver, Ahmad M. Alharbi, Hasan Alfahemi, Ruqaiyyah Siddiqui
Summary: Since the discovery of antibiotics, humans have benefited from decreased morbidity and mortality associated with bacterial infections. However, the misuse of antibiotics has led to the emergence of multi-drug resistant bacterial infections, which is a major health concern. Bacteria exposed to inappropriate levels of antibiotics undergo genetic changes that enable them to survive in the host and become more resistant.
Article
Hematology
Jacob Stauber, John M. Greally, Ulrich Steidl
Summary: This review discusses the role of clonal evolution in hematological malignancies and emphasizes the contribution of the hematopoietic stem cell population in disease progression and relapse. Recent advances and unanswered questions in this field are highlighted.
Article
Medicine, Research & Experimental
Jacqueline A. Odgis, Katie M. Gallagher, Sabrina A. Suckiel, Katherine E. Donohue, Michelle A. Ramos, Nicole R. Kelly, Gabrielle Bertier, Christina Blackburn, Kaitlyn Brown, Lena Fielding, Jessenia Lopez, Karla Lopez Aguiniga, Estefany Maria, Jessica E. Rodriguez, Monisha Sebastin, Nehama Teitelman, Dana Watnick, Nicole M. Yelton, Avinash Abhyankar, Noura S. Abul-Husn, Aaron Baum, Laurie J. Bauman, Jules C. Beal, Toby Bloom, Charlotte Cunningham-Rundles, George A. Diaz, Siobhan Dolan, Bart S. Ferket, Vaidehi Jobanputra, Patricia Kovatch, Thomas V. McDonald, Patricia E. McGoldrick, Rosamond Rhodes, Michael L. Rinke, Mimsie Robinson, Arye Rubinstein, Lisa H. Shulman, Christian Stolte, Steven M. Wolf, Elissa Yozawitz, Randi E. Zinberg, John M. Greally, Bruce D. Gelb, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny
Summary: The NYCKidSeq project aims to contribute innovations and best practices in communicating genomic test results to diverse populations, providing information for implementing genomic medicine in health systems serving diverse populations using methods that are clinically useful, technologically savvy, culturally sensitive, and ethically sound.
Article
Genetics & Heredity
Sabrina A. Suckiel, Jaqueline A. Odgis, Katie M. Gallagher, Jessica E. Rodriguez, Dana Watnick, Gabrielle Bertier, Monisha Sebastin, Nicole Yelton, Estefany Maria, Jessenia Lopez, Michelle Ramos, Nicole Kelly, Nehama Teitelman, Faygel Beren, Tom Kaszemacher, Kojo Davis, Irma Laguerre, Lynne D. Richardson, George A. Diaz, Nathaniel M. Pearson, Stephen B. Ellis, Christian Stolte, Mimsie Robinson, Patricia Kovatch, Carol R. Horowitz, Bruce D. Gelb, John M. Greally, Laurie J. Bauman, Randi E. Zinberg, Noura S. Abul-Husn, Melissa P. Wasserstein, Eimear E. Kenny
Summary: Genomic sequencing is increasingly used to meet the needs of a growing patient population, and GUiA, a web-based application, was developed to effectively deliver genomic results and clinical information. Feedback from NYCKidSeq participants showed positive responses to GUiA, suggesting its utility in communicating complex genomic information effectively among diverse populations.
GENETICS IN MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Devin Rocks, Ivana Jaric, Lydia Tesfa, John M. Greally, Masako Suzuki, Marija Kundakovic
Summary: ATAC-seq is a popular method in neuroscience research, offering advantages of requiring minimal material and capturing a variety of gene regulatory elements. Different freezing methods can impact the results but overall, ATAC-seq coupled with FANS generates consistent and robust data for studying neuronal chromatin accessibility.
Article
Mathematical & Computational Biology
Melissa J. Fazzari, Mimi Y. Kim
Summary: This study examined approaches and guidelines for subgroup analysis to assess heterogeneity of treatment effect in clinical trials, with a focus on non-inferiority (NI) trials. It found that standard statistical tests and machine learning methods have different applications and performances in subgroup analysis, helping to understand the underlying reasons for trial outcomes.
STATISTICS IN MEDICINE
(2021)
Article
Oncology
Parvathi A. Myer, Jessica K. Lee, Russell W. Madison, Kith Pradhan, Justin Y. Newberg, Carmen R. Isasi, Samuel J. Klempner, Garrett M. Frampton, Jeffery S. Ross, Jeffrey M. Venstrom, Alexa B. Schrock, Sudipto Das, Leonard Augenlicht, Amit Verma, John M. Greally, Srilakshmi M. Raj, Sanjay Goel, Siraj M. Ali
Summary: Black people have a higher incidence and worse survival rates for colorectal cancer compared to white people. African descent patients have more frequent genetic alterations, particularly in KRAS, APC, and PIK3CA genes. In young-onset colorectal cancer, there are significant differences in APC mutations between African descent and European descent patients.
Article
Endocrinology & Metabolism
Kassidy Lundy, John F. Greally, Grace Essilfie-Bondzie, Josephine B. Olivier, Reanna Dona-Termine, John M. M. Greally, Masako Suzuki
Summary: Vitamin D plays a critical role in calcium homeostasis, the immune system, and normal development. Many global epidemiological studies have found high prevalence rates of vitamin D deficiency and insufficiency, particularly in reproductive age and pregnant women. This study using a mouse model found that prenatal vitamin D deficiency increases the occurrence of liver histopathological changes and alters gene expression profiles, potentially contributing to offspring health risks.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Genetics & Heredity
Jamie M. Ellingford, Joo Wook Ahn, Richard D. Bagnall, Diana Baralle, Stephanie Barton, Chris Campbell, Kate Downes, Sian Ellard, Celia Duff-Farrier, David R. FitzPatrick, John M. Greally, Jodie Ingles, Neesha Krishnan, Jenny Lord, Hilary C. Martin, William G. Newman, Anne O'Donnell-Luria, Simon C. Ramsden, Heidi L. Rehm, Ebony Richardson, Moriel Singer-Berk, Jenny C. Taylor, Maggie Williams, Jordan C. Wood, Caroline F. Wright, Steven M. Harrison, Nicola Whiffin
Summary: This article discusses genetic variants in non-coding regions and proposes guidelines for defining and interpreting these variants. The aim of these guidelines is to increase the number and range of non-coding region variants that can be clinically interpreted, leading to new diagnoses and the discovery of novel disease mechanisms.
Review
Hematology
Patricia A. Shi, Larry L. Luchsinger, John M. Greally, Colleen S. Delaney
Summary: This review discusses the decline in the use of umbilical cord blood (UCB) as a source of donor hematopoietic stem cells (HSC) for transplantation and emphasizes the potential of UCB and related birthing tissues for a wide range of therapies. When best practices are followed, UCB transplant can provide better survival and decreased risks compared to other donor sources. The review suggests that the potential of UCB for transplant and other cell-based therapies is undervalued and underutilized.
CURRENT OPINION IN HEMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Stacey R. McGee, Shivakumar Rajamanickam, Sandeep Adhikari, Oluwatosin C. Falayi, Theresa A. Wilson, Brian J. Shayota, Jessica A. Cooley Coleman, Cindy Skinner, Raymond C. Caylor, Roger E. Stevenson, Caio Robledo D' Angioli Costa Quaio, Berenice Cunha Wilke, Jennifer M. Bain, Kwame Anyane-Yeboa, Kaitlyn Brown, John M. Greally, Emilia K. Bijlsma, Claudia A. L. Ruivenkamp, Keren Politi, Lydia A. Arbogast, Michael W. Collard, Jodi Huggenvik, Sarah H. Elsea, Philip J. Jensik
Summary: De novo deleterious and heritable biallelic mutations in the DNA binding domain of DEAF1 result in a phenotypic spectrum of neurodevelopmental disorders, affecting genes involved in neuronal function and dendritic spine maintenance. This study expands the clinical spectrum of individuals with DEAF1-associated neurodevelopmental disorders, enhances our understanding of DEAF1's potential roles in neuronal function, and demonstrates the dominant negative activity of de novo variants.
HUMAN MOLECULAR GENETICS
(2023)
Article
Multidisciplinary Sciences
Netha Ulahannan, Ronald Cutler, Reanna Dona-Termine, Claudia A. Simoes-Pires, N. Ari Wijetunga, Matthew McKnight Croken, Andrew D. Johnston, Yu Kong, Shahina B. Maqbool, Masako Suzuki, John M. Greally
Summary: By studying the gene expression and chromatin states of human fibroblasts infected with Toxoplasma gondii, we gained insights into the molecular interactions between the intracellular pathogen and its host cell. We found that host cell genes were activated to regulate cellular processes, some of which were protective of the host cell while others were advantageous to the pathogen. Analysis of the host and parasite genomic information allowed us to annotate the T. gondii genome more accurately and discover new genes and cis-regulatory elements. By inferring the involved transcription factors and cell signaling responses in the host cell, we could understand how T. gondii perturbs host cell physiology.
Article
Rheumatology
Melissa J. Fazzari, Marta M. Guerra, Jane Salmon, Mimi Y. Kim
Summary: This study aimed to improve the prediction of adverse pregnancy outcomes (APO) in patients with systemic lupus erythematosus (SLE) using machine learning approaches and identify other risk factors. By comparing different algorithms, it was found that some machine learning methods and LASSO performed better in predicting APO. However, further research is needed to discover new biomarkers and risk factors for better prediction.
LUPUS SCIENCE & MEDICINE
(2022)
Meeting Abstract
Hematology
Caner Saygin, Jacob Stauber, Ibrahim Aldoss, Adam S. Sperling, Lachelle D. Weeks, Marlise R. Luskin, Todd C. Knepper, Pankhuri Wanjari, Peng Wang, Angela Lager, Jeremy Segal, Benjamin Kaumeyer, Sandeep Gurbuxani, Girish Venkataraman, Jason Xiaojun Cheng, Bartholomew Eisfelder, Oliver Bohorquez, Anand Ashwin Patel, Olatoyosi Odenike, Richard A. Larson, Lucy A. Godley, Daniel A. Arber, Benjamin L. Ebert, John M. Greally, Ulrich G. Steidl, Bijal D. Shah, Wendy Stock
Article
Genetics & Heredity
Kevin M. Bowling, Michelle L. Thompson, Melissa A. Kelly, Sarah Scollon, Anne M. Slavotinek, Bradford C. Powell, Brian M. Kirmse, Laura G. Hendon, Kyle B. Brothers, Bruce R. Korf, Gregory M. Cooper, John M. Greally, Anna C. E. Hurst
Summary: The uptake of exome/genome sequencing has introduced challenges related to unexpected testing results, especially for pediatric patients, sparking debate on whether incidental findings should be returned. Identification and return of non-ACMG-recommended incidental findings in pediatric patients can be complex and difficult. While returning incidental genetic findings can benefit patients and providers, challenges and risks are also present.
Review
Genetics & Heredity
Julia J. Wattacheril, Srilakshmi Raj, David A. Knowles, John M. Greally
Summary: It is believed that environmental influences can affect gene expression by altering epigenetic regulators of transcription. These epigenetic changes can be maintained long term and through cell division, resulting in a prolonged effect of the exposure. The evidence supporting this model comes from the observation of changes in molecular regulators of transcription following exposures. However, this model may be oversimplistic, and further research is needed to fully understand the complex associations between environmental exposures and phenotypes.
