Neural crest progenitor cells were differentiated into smooth muscle cells (green; nucleus of cells stained in pink). Loss of factors underlying genome folding impairs neural crest differentiation into smooth muscle cells.
PHILADELPHIA New research is advancing understanding of certain cancers and complex congenital disorders by illuminating how BRD4, a protein that scientists have studied for years, directs the spatial organization of DNA within the nucleus of the cell, a function critical for stem cell differentiation into muscle cells. Because how DNA folds is central to gene regulation, this study not only has implications that extend to a range of genetic conditionsincluding heart defects, cleft palate, microcephaly and intellectual disabilitiesbut will also better guide development of drug targets for BRD4, some of which are in clinical trials as promising therapeutic interventions to treat cancer and heart disease. The findings are published today in Nature Genetics.
Inhibiting BRD4 and the class of proteins it belongs to has been seen as a very enticing area of cancer research. A similar strategy is being considered for heart disease patients, said senior author Rajan Jain, MD, assistant professor of Medicine and Cell & Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania. Our data highlight the importance of trying to use inhibitors which affect a specific function of BRD4. Its possible that negative results in clinical trials inhibiting BRD4 is because too many functions are being inhibited, so by understanding all the different functions we could be able to eventually have designer drugs which affect one versus another function of BRD4.
An attractive target, but a poorly understood one
BRD4 has been termed a cellular Swiss army knife because of its ability to regulate multiple facets of how a gene is turned on, and normally acts as a positive regulator of processes that allow some genes to be switched on. BRD4 regulates genes including those involved in cell growth and division, and if those genes are switched on abnormally they can drive certain cancers, including several forms of leukemia. Given its pro-growth function, inhibition of BRD4 has seemed a promising strategy for fighting those cancers. However, results from some clinical studies of BRD4 inhibitors have suggested that inhibiting BRD4 could prove to be a complicated affair.
Jains team showed that BRD4s function in genome-folding is distinct from its function in keeping genes switched on. However, in principle, drugs that bind to BRD4 in certain ways could inhibit either or both functions, which means that there is a need to consider medicine that targets one function or another of BRD4 and related proteins.
The inhibitors that block BRD4 are potentially also disrupting the proper folding of DNA in some cells, Jain said. So I think our work here reveals another layer of complexity to this protein, and should be relevant when researchers are trying to interpret their results with BRD4-affecting inhibitors.
Mutations in BRD4 also have been associated with cohesinopathies, a set of congenital syndromes, including Cornelia de Lange Syndrome and Roberts Syndrome, that often severely impair and shorten patients lives. Cohesinopathies occur when there is a dysfunction of cohesin, a multi-protein molecular machine that helps fold and coil DNA within cells. How BRD4 is involved in the workings of cohesin has been largely unknown, until now. In this study, researchers discovered that loss of BRD4 in the neural crest, a subset of highly specialized cells that become tissue in the face, heart, brain and other organs, resulted in embryos that share features similar to those observed in human cohensinopathies.
Jain and his fellow researchers hypothesize that BRD4 tells new cells how to fold their DNA so that the correct genes for that cell type are turned on, and hope to prove or disprove that in upcoming research.
The research was supported by the National Institutes of Health (R01HL139783, F31 HL147416, T32 HL007843, T32 GM008216, R35GM128903, F30HD104360, T32GM008216, F31HD102084, and R35HL140018), the Burroughs Wellcome Foundation, the Allen Foundation, the American Heart Association, the National Science Foundation, and the Sarnoff Foundation.
Penn Medicineis one of the worlds leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of theRaymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nations first medical school) and theUniversity of Pennsylvania Health System, which together form a $8.9 billion enterprise.
The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according toU.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $496 million awarded in the 2020 fiscal year.
The University of Pennsylvania Health Systems patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Centerwhich are recognized as one of the nations top Honor Roll hospitals byU.S. News & World ReportChester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nations first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is powered by a talented and dedicated workforce of more than 44,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2020, Penn Medicine provided more than $563 million to benefit our community.
See the rest here:
- 100 plus years of stem cell research20 years of ISSCR - PMC - March 26th, 2024
- Stem Cell Science and Human Research Studies Ahead of Cargo Arrival - NASA Blogs - February 18th, 2024
- Stem cell research project to launch into space - Fox Weather - January 24th, 2024
- Breakthrough in cancer research opening up stem cell therapy to more people. How you can get involved - 69News WFMZ-TV - January 20th, 2024
- Stem Cell Research Heading to the ISS on Axiom Mission 3 - ISS National Lab - January 18th, 2024
- No, Rep. Steve Scalise Didn't Vote Against Stem Cell Research From Which He Is Now Benefiting - The Dispatch - January 12th, 2024
- Applications are open for the Maryland Stem Cell Research Fund - Technical.ly - January 4th, 2024
- Global Stem Cell Therapy Market to Reach USD 928.6 Million by 2031: Says Allied Market Research - Yahoo Finance - November 19th, 2023
- Current state of stem cell-based therapies: an overview - PMC - November 3rd, 2023
- Dynamic Stem Cell Therapy Uncovers Research in Advance Regenrative Medicine - Yahoo Finance - November 3rd, 2023
- Research Fellow (Aging and Cancer Stem Cell Laboratory ... - Times Higher Education - October 15th, 2023
- Qkine Collaborates with the Cambridge Stem Cell Institute to Facilitate Same-Day Access to Key Research Products for Researchers at the Cambridge... - September 27th, 2023
- Stem cells: a comprehensive review of origins and emerging clinical ... - September 25th, 2023
- Stem Cell Research and Communicating Science | GBH - GBH News - September 20th, 2023
- Stem cell research reveals the earliest stages of a human life - SBS News - September 10th, 2023
- Stem Cell Therapy Market Size 2023 | Innovative Research Methodologies with Emerging Trends and Opportuni - Benzinga - September 10th, 2023
- Autologous Stem Cell and Non-Stem Cell Based Therapies Market Research, Current Trends, Key Industry Play - Benzinga - September 8th, 2023
- Stem Cell Therapy Market 2023 Business Statistics and Research ... - The Knox Student - August 28th, 2023
- Autologous Stem Cell Based Therapies Market Analysis, Research ... - Chatfield News-Record - July 19th, 2023
- Global Stem Cell Market Projected to Reach $14 Bn by 2028: Ken Research - Yahoo Finance - July 11th, 2023
- Theradaptive Awarded Manufacturing Assistance Grant by the Maryland Stem Cell Research Fund - Benzinga - July 10th, 2023
- Bionano Announces Presentation of OGM Utility Across Stem Cell Therapy Applications at the International Society for Stem Cell Research (ISSCR) Annual... - June 19th, 2023
- Sana Biotechnology Highlights Preclinical Data from Hypoimmune and Fusogen Platforms at the International Society for Stem Cell Research (ISSCR) 2023... - June 17th, 2023
- Induced Pluripotent Stem Cell (iPSC) Global Market Report 2023: Effective Research Programs Hold Key in Roll Out of Advanced iPSC Treatments - Yahoo... - June 17th, 2023
- Lung and heart stem cell research paves way for new COVID-19 treatments - Medical Xpress - June 14th, 2023
- Toxicology PhD student cultivating giant leaps in stem cell research ... - June 4th, 2023
- Harvard Stem Cell Institute (HSCI) - May 26th, 2023
- Findings may lead to improved insulin-secreting cells derived from stem ... - May 26th, 2023
- Cell Press: Stem Cell Reports - May 26th, 2023
- Stem cell research could enable blood to be made in other parts of the body - Medical Xpress - May 26th, 2023
- Construction of myocardial patch with mesenchymal stem cells and poly ... - May 22nd, 2023
- Cedars-Sinai to Send Stem Cells to the Space Station to Aid in the ... - May 22nd, 2023
- researchers expand human blood stem cells | Institute for Stem Cell ... - May 22nd, 2023
- A Look Inside Stem Cells Helps Create Personalized Regenerative ... - May 17th, 2023
- Exclusive Research Report on Msenchymal Stem Cell and Exosome Diagnostics and Therapies Market to Witness Comp - openPR - May 17th, 2023
- The Future of Stem Cell Research: Master of Science in ... - The Daily | Case Western Reserve University - May 10th, 2023
- Exclusive Research Report on Stem Cell Therapy for Diabetes and ... - Digital Journal - May 9th, 2023
- Aging melanocyte stem cells and gray hair | National Institutes of ... - May 5th, 2023
- Mouse hair turns gray when certain stem cells get stuck - May 5th, 2023
- Science-First Skincare Company Michal Morrison Secures Exclusive World-Wide License of Proprietary STEM6 Molecule, Supported by Over 25 Years of... - May 5th, 2023
- BioCentriq and panCELLa execute research agreement to study stem cell-derived Natural Killer cell expansi - Benzinga - May 3rd, 2023
- Hair turning gray? Study finds a stem cell 'glitch' may be the cause - May 1st, 2023
- Elevai Labs Announces Research Grant Award and Partnership to Better Characterize the 'Payload' of ELEVAI's Stem Cell-derived Exosomes - Yahoo Finance - April 27th, 2023
- Why does hair turn gray? A new study says 'stuck' stem cells may ... - NPR - April 27th, 2023
- Study advances understanding of how melanocyte stem cells work to color ... - April 21st, 2023
- Stem cell research and therapy legislation to be replaced, says ... - Bahamas Tribune - April 21st, 2023
- Stem Cell Research (journal) - Wikipedia - April 21st, 2023
- Scientists Are About to Try to Create Stem Cells in Space - April 21st, 2023
- Stem Cell Research & Therapy | Articles - BioMed Central - April 16th, 2023
- Stem Cell Junk Yards Reveal a New Clue About Aging | WIRED - April 16th, 2023
- Global Stem Cells Market Research Report 2023: Implications - April 16th, 2023
- Stem cell research can help people with hard- | EurekAlert! - April 16th, 2023
- University Of Edinburgh's stem cell research gets funding boost - India Education Diary - April 14th, 2023
- Two major stem cell research projects supported with more than ... - University of California, Santa Cruz - April 8th, 2023
- Cancer detection predicts tumors before they form: discovery - March 29th, 2023
- Stem cell therapy: a potential cure for hearing loss? - March 29th, 2023
- Turkey's Only Stem Cell Production Application and Research Center - Expat Guide Turkey - March 24th, 2023
- Stem Cell Research Article, Embryonic Cells Information, Cell Therapy ... - March 24th, 2023
- Scientists create mice with cells from 2 males for 1st time - March 19th, 2023
- QBRI concludes stem cells symposium - Gulf Times - March 17th, 2023
- 2020 California Proposition 14 - Wikipedia - March 17th, 2023
- Stem Cell Reports | Journal | ScienceDirect.com by Elsevier - March 17th, 2023
- Stem cell therapy MSC-NP found to ease inflammatory activity of brain ... - March 12th, 2023
- Stem Cell Research | Office of Research Compliance | SIU - March 12th, 2023
- Heart disease study shows hope for stem cell treatment - March 4th, 2023
- Stem cells drive antler regeneration | Science - March 4th, 2023
- Stem Cell Research: Argumentative Essay - Free Essay Example - Edubirdie - March 4th, 2023
- Stem Cell Research | Thermo Fisher Scientific - US - March 4th, 2023
- Stem cell controversy - Wikipedia - February 28th, 2023
- National Institutes of Health grant funds interdisciplinary ... - February 27th, 2023
- Research Associate in Cancer Stem Cell Research job with ... - Times Higher Education - February 25th, 2023
- Pioneering Stem Cell Research Conference at The Aga Khan ... - The Aga Khan University - February 25th, 2023
- Scientists grapple with ethics of stem cell research - STAT - February 17th, 2023
- Research Associate in Stem Cell Neurobiology job with KINGS ... - Times Higher Education - January 30th, 2023
- Stem cells: past, present, and future | Stem Cell Research & Therapy ... - January 12th, 2023
- Edu Thesis & Essay: Stem cell research outline top writers online! - January 12th, 2023
- Stem Cell Biology Research Program | Johns Hopkins Institute for Cell ... - January 5th, 2023
- Stem cell population identified is vital for bone regeneration: Research - ThePrint - January 5th, 2023
- Leading scientist 'blown away' by UAE advances in stem cell research - The National - December 15th, 2022
- The Stem Cell Assay Market Is Set To Grow At A 20% Annual Rate, Due To The High Prevalence Of Chronic Diseases As Per The Business Research Company's... - December 13th, 2022
Recent Comments