Research led by Muhammad Riaz, PhD, Jinkyu Park, PhD, and Lorenzo Sewanan, MD, PhD, from the Qyang and Campbell laboratories at Yale, provides a mechanism to identify abnormalities linked with a hereditary cardiac condition, hypertrophic cardiomyopathy (HCM), in which walls of the left ventricle become abnormally thick and often stiff. The findings appear in the journal Circulation.
Patients with familial HCM have an increased risk of sudden death, heart failure, and arrhythmias. HCM is the most common inherited cardiac disease, affecting one in 500 people. The disease is thought to be caused by mutations that regulate cardiac muscle contraction, compromising the hearts ability to pump blood. However, the mechanisms behind the disease are poorly understood.
For this multi-model study, the researchers used stem cell approaches to understand the mechanisms that drive inherited HCM. The technology, induced pluripotent stem cells (iPSCs), can accelerate insights into the genetic causes of disease and the development of new treatments using the patients own cells.
This is a humbling experience that a patients disease phenotypes teach researchers fundamental basic knowledge that sets the stage for innovative new therapies. Furthermore, our research has established a great model to assist many physicians at Yale School of Medicine and Yale New Haven Hospital to unravel mechanistic insights into disease progression using the patients own iPSCs and engineered tissues, said Yibing Qyang, PhD, associate professor of medicine (cardiology) and of pathology.
We wanted to understand the disease mechanism and find a new therapeutic strategy, Park said.
The concept originated with an 18-month-old patient who suffered from familial HCM. Through a collaboration with Daniel Jacoby, MD, adjunct associate professor of cardiovascular medicine and an expert on HCM, who provided medical care for this patient, Park and the team used stem cell technologies to address a fundamental question, the disease mechanisms behind HCM. They collected 10 cc of the patients blood and introduced stem cell factors into the blood cells to generate self-renewable iPSCs. By applying cardiac knowledge, they coaxed iPSCs into patients own cardiomyocytes (heart cells) for cardiac disease studies. We discovered a general mechanism which explains the disease progression, said Park.
Next, they engineered heart tissues that resembled the early-onset disease scenario of the young patient. The disease was a severe presentation at the age of 18 months, which suggested that the disease started at the fetal/neonatal stage.
The next phase of the study was to recreate a 3-D model that was used to mimic the progression of the disease, including mechanical properties such as contraction and force production of that muscle, to understand how much force is compromised if the mutation is present. This was performed in collaboration with Stuart Campbell, PhD, and Sewanan from Yales Department of Biomedical Engineering. Coupled with computational modeling for muscle contraction, the authors developed robust systems that allowed them to examine the biomechanical properties of the tissue at three-dimensional levels.
Finally, using advanced gene editing technologies, the research team modified these mutations. They discovered that after the mutations were corrected, the disease was reversed. These insights about sarcomeric protein mutations could lead to novel therapeutics for HCM and other diseases. The interaction between mutations could also suggest that the same biomechanical mechanism exists in other conditions such as ischemic heart disease.
We can apply these findings to cardiac conditions associated with hypertension, diabetes, or aging, said Riaz.
One of the fundamental challenges was that we needed to generate iPSCs from the patients family, Riaz added. Using this technology, Park was able to recreate primary cells from the cells of a patient with HCM, a process which takes over a month. Riaz and Park used stem cells to identify the vital role of pathological tissue remodeling, which is caused by sarcomeric hypertrophic cardiomyopathy mutations.
We are hopeful that our findings will be replicated in the scientific community, said Riaz. This is an example of bed to bench research, where scientists extract materials from clinics and conduct the experiment in the laboratory and then discover new methods to treat patients.
The authors also noted that RNA sequencing could be used as a guide to characterize the disease at a molecular level. Scientists may be able to identify more targeted drugs by examining the biomechanical properties of the tissue. We can now screen multiple drugs to see whether any of those drugs are able to rescue the phenotype, they said.
Riaz, now an associate research scientist in the Qyang lab, began as a cancer researcher. He earned a PhD from the Erasmus University Medical Center, based in Rotterdam, Netherlands. He later studied genetic disorders in skeletal muscle disease before joining the lab in 2017.
Park, also from the Qyang lab, graduated from Seoul National University, South Korea in 2013. He completed postdoctoral research at the University of Missouri where he focused on vascular biology and emerging areas in stem cell technology.
Yales Lorenzo R. Sewanan, MD, PhD, Yongming Ren, PhD, Jonas Schwan, PhD, Subhash K. Das, PhD, Pawel T. Pomianowski, MD, Yan Huang, PhD, Matthew W. Ellis, BS, Jiesi Luo, PhD, Caihong Qiu, PhD, George Tellides, MD, PhD, John Hwa, MD, PhD, Lawrence H. Young, MD, Daniel L. Jacoby, MD, and Yibing Qyang contributed to this study. Additional coauthors are Indiana Universitys Juli Liu, PhD and Lei Yang, PhD; Columbia Universitys Loujin Song, PhD, Masayuki Yazawa, PhD, and I-Ping Chen, DDS, PhD.
Funding for the research came, in part, from the National Institutes of Health, Department of Defense, and the American Heart Association.
Read more:
Uncovering New Approaches to a Common Inherited Heart Disorder - Yale School of Medicine
- Vascular Cell and Molecular Biology | Center for Vascular Biology | Weill Cornell ... [Last Updated On: April 13th, 2018] [Originally Added On: April 13th, 2018]
- APVBO-Asia Pacific Vascular Biology Organization Conference [Last Updated On: April 18th, 2018] [Originally Added On: April 18th, 2018]
- Vascular Biology Conferences | Vascular Surgery ... [Last Updated On: May 5th, 2018] [Originally Added On: May 5th, 2018]
- Vascular Discovery: From Genes to Medicine [Last Updated On: May 7th, 2018] [Originally Added On: May 7th, 2018]
- 2019 Vascular Cell Biology Conference GRC [Last Updated On: May 26th, 2018] [Originally Added On: May 26th, 2018]
- Biology 211: Taxonomy of Flowering Plants [Last Updated On: June 7th, 2018] [Originally Added On: June 7th, 2018]
- esm-evbo2019.org - Menu [Last Updated On: July 27th, 2018] [Originally Added On: July 27th, 2018]
- Vascular Biology | Pulmonary, Allergy, Sleep & Critical ... [Last Updated On: November 16th, 2018] [Originally Added On: November 16th, 2018]
- Lower vascular plant | biology | Britannica.com [Last Updated On: November 18th, 2018] [Originally Added On: November 18th, 2018]
- Vascular Biology - NAVBO [Last Updated On: November 20th, 2018] [Originally Added On: November 20th, 2018]
- 2019 Cerebral Vascular Biology Conference - cvent.com [Last Updated On: November 21st, 2018] [Originally Added On: November 21st, 2018]
- PPARs and Their Emerging Role in Vascular Biology ... [Last Updated On: November 26th, 2018] [Originally Added On: November 26th, 2018]
- Vascular Biology Chicago Medicine [Last Updated On: November 30th, 2018] [Originally Added On: November 30th, 2018]
- Vascular Biology | Society for Vascular Surgery [Last Updated On: November 30th, 2018] [Originally Added On: November 30th, 2018]
- Vascular Biology 2018 - NAVBO [Last Updated On: December 19th, 2018] [Originally Added On: December 19th, 2018]
- Vascular Biology 2019 - NAVBO [Last Updated On: December 20th, 2018] [Originally Added On: December 20th, 2018]
- Vascular Biology [Last Updated On: January 22nd, 2019] [Originally Added On: January 22nd, 2019]
- pvb2019.org Plant Vascular Biology Conference 2019 [Last Updated On: January 31st, 2019] [Originally Added On: January 31st, 2019]
- Plant Physiology | Basic Biology [Last Updated On: March 12th, 2019] [Originally Added On: March 12th, 2019]
- Awards - esm-evbo2019.org [Last Updated On: April 23rd, 2019] [Originally Added On: April 23rd, 2019]
- Medication and Exercise to Prevent Muscle Loss - Next Avenue [Last Updated On: September 24th, 2019] [Originally Added On: September 24th, 2019]
- A Snail as Fast as a Bullet, and Other Darwin-Defying Marvels - Discovery Institute [Last Updated On: September 24th, 2019] [Originally Added On: September 24th, 2019]
- Nature up close: Life in the Humboldt Penguin National Reserve - CBS News [Last Updated On: September 24th, 2019] [Originally Added On: September 24th, 2019]
- Oklahoma new hires and promotions announced - Oklahoman.com [Last Updated On: September 24th, 2019] [Originally Added On: September 24th, 2019]
- Quinn Capers IV, MD - TCTMD [Last Updated On: September 24th, 2019] [Originally Added On: September 24th, 2019]
- Cardiovascular Repair And Reconstruction Devices Market Global Industry Insights by Top Vendors, Growth, Revenue and Forecast Outlook 2019-2025 -... [Last Updated On: September 26th, 2019] [Originally Added On: September 26th, 2019]
- Four health projects at Boston Childrens Hospital that could help adults - The Boston Globe [Last Updated On: September 30th, 2019] [Originally Added On: September 30th, 2019]
- Research Officer/ Postdoctoral Researcher - The Conversation AU [Last Updated On: October 16th, 2019] [Originally Added On: October 16th, 2019]
- UNSW skin cancer researcher Levon Khachigian hit with string of retractions - ABC News [Last Updated On: October 16th, 2019] [Originally Added On: October 16th, 2019]
- Michal Wszola: We Expect to Transplant the Bioprinted Bionic Pancreas in Three to Five Years - 3DPrint.com [Last Updated On: October 24th, 2019] [Originally Added On: October 24th, 2019]
- 'The Blob': This mysterious 'smart' slime can solve puzzles and make decisions - CNBC [Last Updated On: October 24th, 2019] [Originally Added On: October 24th, 2019]
- University of Maryland and DOD collaborate to study Tick-borne Infections using 3-D models of human blood vessels - Outbreak News Today [Last Updated On: November 19th, 2019] [Originally Added On: November 19th, 2019]
- Submerged Vegetation Mirrors Coast's Health - Coastal Review Online [Last Updated On: November 19th, 2019] [Originally Added On: November 19th, 2019]
- Another health warning for e-cigarette users that has nothing to do with lung disease - MarketWatch [Last Updated On: November 19th, 2019] [Originally Added On: November 19th, 2019]
- E-Cigarettes Take a Dangerous Toll on Heart Health - DocWire News [Last Updated On: November 19th, 2019] [Originally Added On: November 19th, 2019]
- Vascular biology Department of Surgery College of ... [Last Updated On: November 19th, 2019] [Originally Added On: November 19th, 2019]
- US Nobel laureates tell us what they think about cancer research, moonshots, the dark side, funding, meritocracy, herd mentality, Trump, and joy - The... [Last Updated On: November 21st, 2019] [Originally Added On: November 21st, 2019]
- Growing Organs in the Lab: One Step Closer to Reality - BioSpace [Last Updated On: November 21st, 2019] [Originally Added On: November 21st, 2019]
- Inotrem Announces Enrollment of First Patient in its Phase IIb ASTONISH Trial for Nangibotide in the Treatment of Septic Shock - Business Wire [Last Updated On: November 21st, 2019] [Originally Added On: November 21st, 2019]
- Another Study Suggests E-cigarettes Hurt Heart Health More Than Regular Cigarettes - Science Times [Last Updated On: November 21st, 2019] [Originally Added On: November 21st, 2019]
- Cleveland Clinic awarded $12 million by NIH to study the link between gut microbes and heart disease - Crain's Cleveland Business [Last Updated On: November 21st, 2019] [Originally Added On: November 21st, 2019]
- JanOne Acquires Worldwide, Exclusive License for Promising Treatment of Peripheral Arterial Disease (PAD) - Yahoo Finance [Last Updated On: November 27th, 2019] [Originally Added On: November 27th, 2019]
- Germ-free lungs of newborn mice are partially protected against hyperoxia - The Mix [Last Updated On: November 27th, 2019] [Originally Added On: November 27th, 2019]
- Bethesda Health Physician Group Welcomes Fellowship-Trained Endocrine Surgeon Jessica L. Buicko, MD, to Its Team - The Boca Raton Tribune [Last Updated On: November 27th, 2019] [Originally Added On: November 27th, 2019]
- 9 Harvard researchers named AAAS Fellows Harvard - Harvard Gazette [Last Updated On: November 27th, 2019] [Originally Added On: November 27th, 2019]
- Top Technical Advances of 2019 - The Scientist [Last Updated On: December 29th, 2019] [Originally Added On: December 29th, 2019]
- Growing up Tyrannosaurus rex: Osteohistology refutes the pygmy Nanotyrannus and supports ontogenetic niche partitioning in juvenile Tyrannosaurus -... [Last Updated On: January 2nd, 2020] [Originally Added On: January 2nd, 2020]
- UCC currently taking applicants for 21 jobs with some incredible pay - Cork Beo [Last Updated On: January 2nd, 2020] [Originally Added On: January 2nd, 2020]
- Vascular Biology | Surgery Research | Michigan Medicine ... [Last Updated On: January 2nd, 2020] [Originally Added On: January 2nd, 2020]
- Sandy Bottom wetlands to receive protection for 'national ecological significance' - Citizen Times [Last Updated On: January 14th, 2020] [Originally Added On: January 14th, 2020]
- Why biotech is a boon for patients and investors - Spear's WMS [Last Updated On: January 14th, 2020] [Originally Added On: January 14th, 2020]
- Exonate Announces Collaboration With Janssen to Develop a New Eye Drop for the Treatment of Retinal Vascular Diseases Including Wet Age-related... [Last Updated On: January 14th, 2020] [Originally Added On: January 14th, 2020]
- G-protein Coupled Receptor Market Competitive Research And Precise Outlook 2019 To 2025 Dagoretti News - Dagoretti News [Last Updated On: January 18th, 2020] [Originally Added On: January 18th, 2020]
- Scientists revealed the oldest known scorpion on Earth - Tech Explorist [Last Updated On: January 18th, 2020] [Originally Added On: January 18th, 2020]
- How biology creates networks that are cheap, robust, and efficient - Penn: Office of University Communications [Last Updated On: January 18th, 2020] [Originally Added On: January 18th, 2020]
- Genome editing heralds new era of disease research, therapy - The Augusta Chronicle [Last Updated On: January 18th, 2020] [Originally Added On: January 18th, 2020]
- Research Fellow in Vascular Stem Cell Biology job with QUEENS UNIVERSITY BELFAST | 195527 - Times Higher Education (THE) [Last Updated On: February 10th, 2020] [Originally Added On: February 10th, 2020]
- More than skin deep: the latest innovation in 3D printing - Med-Tech Innovation [Last Updated On: February 10th, 2020] [Originally Added On: February 10th, 2020]
- Examining the link between menopause and heart disease risk - Medical News Bulletin [Last Updated On: February 10th, 2020] [Originally Added On: February 10th, 2020]
- Women Face an Increased Risk of Heart Disease With AgeRunning Can Help - runnersworld.com [Last Updated On: February 12th, 2020] [Originally Added On: February 12th, 2020]
- G-protein Coupled Receptor Market Competitive Research And Precise Outlook 2019 To 2025 - Galus Australis [Last Updated On: February 15th, 2020] [Originally Added On: February 15th, 2020]
- Valentine's Day Matters of the Heart, Biopharma-Style - BioSpace [Last Updated On: February 15th, 2020] [Originally Added On: February 15th, 2020]
- The Addicted Gardener: Environmental tidbits from around the world - Wicked Local Sharon [Last Updated On: February 22nd, 2020] [Originally Added On: February 22nd, 2020]
- UI at 150 & Beyond: 'The Quad was the best no matter what the weather' - Champaign/Urbana News-Gazette [Last Updated On: February 22nd, 2020] [Originally Added On: February 22nd, 2020]
- The Addicted Gardener: Environmental tidbits from around the world - Wicked Local Dedham [Last Updated On: February 23rd, 2020] [Originally Added On: February 23rd, 2020]
- THE ADDICTED GARDENER: Environmental tidbits from around the world - Wicked Local Wareham [Last Updated On: March 22nd, 2020] [Originally Added On: March 22nd, 2020]
- 'Little Foot' skull reveals how this more than 3 million year old human ancestor lived - HeritageDaily [Last Updated On: March 22nd, 2020] [Originally Added On: March 22nd, 2020]
- It's Not Only About Neurons - The Good Men Project [Last Updated On: March 22nd, 2020] [Originally Added On: March 22nd, 2020]
- Who is Sir Patrick Vallance and what is his role in government during coronavirus outbreak? - The Scottish Sun [Last Updated On: March 22nd, 2020] [Originally Added On: March 22nd, 2020]
- University of Washington Pathology Professor Dies of COVID-19 - The Scientist [Last Updated On: March 22nd, 2020] [Originally Added On: March 22nd, 2020]
- THE ADDICTED GARDENER: Environmental tidbits from around the world - Wicked Local Rochester [Last Updated On: March 23rd, 2020] [Originally Added On: March 23rd, 2020]
- Ancient human ancestor 'Little Foot' probably lived in trees, new research finds - WBAP News/Talk [Last Updated On: March 23rd, 2020] [Originally Added On: March 23rd, 2020]
- Study shows similarity in anti-VEGF injection intervals for wet AMD - Ophthalmology Times [Last Updated On: March 25th, 2020] [Originally Added On: March 25th, 2020]
- aTyr Pharma and its Hong Kong Subsidiary, Pangu BioPharma, Announce Government Grant to Fund Bispecific Antibody Development Platform - BioSpace [Last Updated On: March 25th, 2020] [Originally Added On: March 25th, 2020]
- Health researchers find solution to life-threatening side effect - Mirage News [Last Updated On: March 25th, 2020] [Originally Added On: March 25th, 2020]
- European Vascular Biology Organisation | Advancing human ... [Last Updated On: March 25th, 2020] [Originally Added On: March 25th, 2020]
- Vascular Biology Program | Boston Children's Hospital [Last Updated On: March 25th, 2020] [Originally Added On: March 25th, 2020]
- Vascular Biology Research Program | Johns Hopkins ... [Last Updated On: March 25th, 2020] [Originally Added On: March 25th, 2020]
- Anatomy of a heatwave: how Antarctica recorded a 20.75C day last month - The Conversation AU [Last Updated On: April 1st, 2020] [Originally Added On: April 1st, 2020]
- Who is Sir Patrick Vallance and is he speaking at todays government coronavirus press briefing? - The Sun [Last Updated On: April 1st, 2020] [Originally Added On: April 1st, 2020]