Euan Ashley

Last updated

Euan Ashley
Euan Angus Ashley.jpg
Alma mater
Known for Genomics, Precision medicine, MyHeart Counts
AwardsFellow of the Royal College of Physicians, National Innovation Award, American Heart Association NIH Director's New Innovator Award, AHA Council on Genomic and Precision Medicine Medal of Honor, Guggenheim Fellowship Award
Scientific career
Institutions
Thesis Nitric oxide and cardiac function  (2002)
Doctoral advisor Barbara Casadei
Other academic advisors Hugh Watkins
Website ashleylab.stanford.edu

Euan Angus Ashley is a Scottish physician, scientist, author, and founder based at Stanford University in California where he is the Arthur L. Bloomfield Chair of the Department of Medicine. [1] He is known for helping establish the field of precision medicine.

Contents

Education and early life

Ashley was born and raised in the West of Scotland and attended Kelvinside Academy in Glasgow. As a teenager, he programmed computers and read popular science books on genetics. He studied Physiology and Medicine at the University of Glasgow graduating with 1st class Honors. He completed residency training at the Oxford Deanery [2] and received his Doctorate (DPhil) from the University of Oxford (Christ Church College). At Stanford University in California, he completed post-doctoral research and specialized training in cardiology, joining the faculty in 2006. He was appointed Associate Dean in 2020.

Leadership

Stanford Department of Medicine

Ashley is the Chair of the Department of Medicine at Stanford. [3] It is the University’s largest department with 15 divisions, over 800 faculty, 500 trainees, and 1200 academic and administrative staff.

Stanford Center for Inherited Cardiovascular Disease

Ashley founded the Center for Inherited Cardiovascular Disease in 2009. [4] [5] It grew out of a clinic established with Heidi Salisbury RN [6] in 2006. The Center is one of the largest in the world providing integrated care for patients with inherited cardiovascular diseases like cardiomyopathy, channelopathy, familial lipoprotein syndromes, aortopathies and neuromuscular disease. An annual fundraising run includes patients, faculty, staff and silicon valley celebrities like Mark Zuckerberg. [7] In 2023, Victoria Parikh [8] took over as director.

Research

Genomics

Ashley is best known for his study of the human genome. [9] [10] [11] [12] In 2009, he led the team that carried out the first medical interpretation of a human genome. [9] The work published in The Lancet laid out a general framework for the medical analysis of a complete human genome and applied this framework to the genome of his Stanford colleague, Stephen Quake. Quake had invented a technology to sequence his own genome, becoming the fifth individual in the world to be sequenced. The landmark medical analysis was reported in news media internationally and was later featured in the Smithsonian museum.

In 2010, Ashley's team carried out the first whole-genome molecular autopsy [13] generating data from the same Helicos sequencing technology of post-mortem cardiac tissue from a patient who died suddenly at a young age of presumed cardiac cause.

In 2011, his team developed a framework for family-based medical genome analysis. [14] The West family were the first family to have their genomes sequenced and were four of the ten individuals sequenced as part of Illumina’s personal genome sequencing project. Other individuals in this first group of ten included Illumina CEO Jay Flatley and the actress Glenn Close. The computational tools developed by Ashley's team included inheritance tools for mendelian diagnosis in trios and quartets, family based polygenic risk scores, whole genome phasing, HLA typing, and automated star-allele calling for pharmacogenomics.

Over the following years, Ashley's team helped establish genome sequencing as a fundamental tool for diagnosis in clinical medicine. In 2014, they reported in the Journal of the American Medical Association a study of genome sequencing in primary care, demonstrating early detection of pathogenic variations in the breast and ovarian cancer gene BRCA2 , and delivering tools for cardiometabolic polygenic risk scoring, and pharmacogenomics. This work also introduced quality-coverage metrics. Ashley was interviewed for NPR's Morning Edition .

In 2017, Ashley's team made the first medical diagnosis using long-read sequencing in a patient with Carney complex whose targeted Sanger sequencing and short read whole genome sequencing had been unrevealing. Developing a pipeline for clinical diagnosis based on aligning, variant calling and filtering Pacific Biosciences SMRT sequencing data, the team identified a previously unrecognized 2 kilobase deletion in PRKAR1A, the gene responsible for Carney complex.

In 2018, as the first co-chair of the steering committee of the Undiagnosed Diseases Network (UDN) [15] [16] Ashley led the network's analysis published in the New England Journal of Medicine that reported an overall diagnosis rate of 35%, estimated significant cost savings from early application, and defined 31 new medical syndromes. This was reported widely including on CBS This Morning , NPR's Morning Edition, and the New York Times where it featured in a segment titled This Week in Good News.

In 2022 Ashley and his research team developed ultra-rapid nanopore genome sequencing for critically ill patients. [17] Published in the New England Journal of Medicine and Nature Biotechnology, the team showed that a genetic diagnosis from whole genome sequencing was possible in as little as 7 hours and 18 minutes. [18] [19] This achievement was recognized by the National Institute for Standards and Technology as well as by Guinness World Records who awarded the team a new record for “fastest DNA sequencing technique.” [20] Ashley appeared on NBC Evening News to discuss the findings.

Cardiovascular science

Ashley's group has also contributed to the foundational science underlying the development of heart transplant donation after cardiac death (DCD) much of that work performed in the same building at Stanford in which heart transplantation was first developed by Norman Shumway.

Awards and honors

Ashley is a recipient of the National Innovation Award from the American Heart Association (AHA) as well as the National Institutes of Health (NIH) Director's New Innovator Award. In 2017, he was recognized by the Obama White House for contributions to personalized and precision medicine. In 2019, he was awarded the American Heart Association Medal of Honor for Genomics and Precision Medicine. In 2021, he became the first holder of the Roger and Joelle Burnell Chair in Genomics and Precision Health at Stanford University. In April 2023, he was awarded the Guggenheim Fellowship, [21] [22] a prestigious honor recognizing mid-career scholars, artists, and scientists who have demonstrated a previous capacity for outstanding work and continue to show exceptional promise.

Scientific publications

Ashley has co-authored over 400 peer reviewed publications. [23]

Books

Cardiology Explained

In 2004, Ashley published the textbook Cardiology Explained [24] along with co-author Josef Niebauer (Remedica, London). According to the publisher's notes, the title “...explains the basic physiology and pathophysiologic mechanisms of cardiovascular disease in a straightforward and diagrammatic manner, gives guidelines as to when referral is appropriate, and, uniquely, explains what the specialist is likely to do.”

The Genome Odyssey

Ashley released the non-fiction title The Genome Odyssey: Medical Mysteries and the Incredible Quest to Solve Them [25] [26] on February 23, 2021, with Celadon Books, a division of Macmillan Publishers. The book features stories of patients and families from Ashley's medical practice and walks through the science underlying those diseases, shining a spotlight on some of the scientists. New York Times best-selling author Abraham Verghese remarked that The Genome Odyssey was “destined to be a landmark narrative in the canon of modern science.” The Pulitzer prize winning author Siddartha Muhkerjee wrote that “Dr Ashley, one of the pioneers of gene sequencing technologies, writes with authority, elegance and simplicity.” The Wall Street Journal described The Genome Odyssey as an “impassioned, firsthand account of the effort to bring genomic data into clinical practice.”

Media

Ashley has appeared on National Public Radio in the United States as well as the BBC radio, Japanese and Indian national television, and NBC Evening News. His work has been covered in print by The New York Times , The Wall Street Journal , The Guardian , The Times of London , The Economist , The Daily Telegraph , Technology Review , and others. His work with the Undiagnosed Diseases Network was covered by National Public Radio [27] and The New York Times . [28]

Startup companies

Ashley is co-founder of multiple companies.

Personalis

In 2012, Ashley co-founded Personalis, [29] a genome-scale diagnostics company with Stanford colleagues Russ Altman, Atul Butte, Mike Snyder and businessman John West. West was the former CEO of Solexa and managed the sale of its core business to Illumina, Inc. In a 2021 earnings call, CEO John West stated that Personalis has sequenced more genomes than any other private company in the US. The company focuses on cancer diagnostics.

Deepcell

Ashley co-founded Deepcell [30] along with Maddison Masaeli (a former post doc in his lab) and Mahyar Salek (a computer scientist). Deepcell develops imaging and microfluidics platforms that use artificial intelligence to identify and isolate viable cells based on morphological distinctions.

Svexa

Ashley is co-founder and chairman of the board at Silicon Valley Exercise Analytics (Svexa), [31] a sports intelligence company that combines physical, subjective and biological data to offer optimized training, performance and recovery recommendations for athletes and teams. He co-founded Svexa with Mikael Mattson, a Swedish physiologist who completed part of his PhD in Ashley's lab, Daryl Waggott who worked as a computational biologist in Ashley's lab, and Filip Larsen, a longtime collaborator of Mattson.

Company boards

AstraZeneca

Ashley was appointed as a Non-Executive Director of the pharmaceutical company AstraZeneca in October 2020. [32] In July 2021, the company acquired Boston-based rare disease company Alexion in a $40 billion deal. During the pandemic, the company licensed a COVID vaccine from the University of Oxford and distributed more than 3 billion doses of the vaccine globally mostly to low- and moderate-income countries. According to company statements, close to 2 billion doses were distributed at cost.

Svexa

Ashley is Chairman of the Board of the sports intelligence company Svexa.

Music

Ashley learned jazz saxophone as a teenager and joined Scotland's regional youth jazz orchestra including tours to the Montreux Jazz Festival, Poland and the USA. Forming a jazz saxophone quartet with members of its saxophone section, The Hung Drawn Quartet featured Ashley, Raymond MacDonald, Graeme Wilson and Allon Beauvoisin and performed a mix of original compositions and arrangements of jazz standards. They released two albums (Cookin' with the HDQ and A Train in the Distance) appeared multiple times on BBC Radio and contributed an arrangement of Charlie Mingus’ Haitian Fight Song to the David Byrne-produced soundtrack for the movie Young Adam featuring Ewan McGregor, Tilda Swinton, and Emily Mortimer. They toured in the US (Philadelphia, New York) and Ontario, Canada in 1994. Ashley also performed in duo and quartet format at the Glasgow International Jazz Festival with Malcolm Finlay, Stuart Brown and others as part of the group Universal.

While at Oxford University, Ashley directed the Oxford University Jazz Orchestra a period of tenure that included band tours to the Glasgow International Jazz Festival, honors at the BBC big band competition, and the release of the live album Know Where you Are with bebop legend Peter King.

During this time, Ashley also acted as soloist for a performance of the Glazounov Saxophone Concerto by the Radcliffe Orchestra in Oxford. [33]

In California, Ashley has performed with jazz group The Jazz Factory and with an Oakland-based Afro-Peruvian jazz collective.

Personal life

Ashley lives in Stanford, California with his wife, Fiona, and their three children. According to his Stanford biography, he is also a private pilot.

Related Research Articles

<span class="mw-page-title-main">Coronary artery disease</span> Reduction of blood flow to the heart

Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of heart disease involving the reduction of blood flow to the cardiac muscle due to a build-up of atheromatous plaque in the arteries of the heart. It is the most common of the cardiovascular diseases. CAD can cause stable angina, unstable angina, myocardial ischemia, and myocardial infarction.

<span class="mw-page-title-main">Human genome</span> Complete set of nucleic acid sequences for humans

The human genome is a complete set of nucleic acid sequences for humans, encoded as the DNA within each of the 24 distinct chromosomes in the cell nucleus. A small DNA molecule is found within individual mitochondria. These are usually treated separately as the nuclear genome and the mitochondrial genome. Human genomes include both protein-coding DNA sequences and various types of DNA that does not encode proteins. The latter is a diverse category that includes DNA coding for non-translated RNA, such as that for ribosomal RNA, transfer RNA, ribozymes, small nuclear RNAs, and several types of regulatory RNAs. It also includes promoters and their associated gene-regulatory elements, DNA playing structural and replicatory roles, such as scaffolding regions, telomeres, centromeres, and origins of replication, plus large numbers of transposable elements, inserted viral DNA, non-functional pseudogenes and simple, highly repetitive sequences. Introns make up a large percentage of non-coding DNA. Some of this non-coding DNA is non-functional junk DNA, such as pseudogenes, but there is no firm consensus on the total amount of junk DNA.

<span class="mw-page-title-main">Genomics</span> Discipline in genetics

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<span class="mw-page-title-main">Personalized medicine</span> Medical model that tailors medical practices to the individual patient

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<span class="mw-page-title-main">Whole genome sequencing</span> Determining nearly the entirety of the DNA sequence of an organisms genome at a single time

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<span class="mw-page-title-main">Exome sequencing</span> Sequencing of all the exons of a genome

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<span class="mw-page-title-main">$1,000 genome</span> Era of predictive and personalized medicine

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<span class="mw-page-title-main">Genomics England</span> UK government-owned company

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The 100,000 Genomes Project is a now-completed UK Government project managed by Genomics England that is sequencing whole genomes from National Health Service patients. The project is focusing on rare diseases, some common types of cancer, and infectious diseases. Participants give consent for their genome data to be linked to information about their medical condition and health records. The medical and genomic data is shared with researchers to improve knowledge of the causes, treatment, and care of diseases. The project has received over £300 million from public and private investment.

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Elective genetic and genomic testing are DNA tests performed for an individual who does not have an indication for testing. An elective genetic test analyzes selected sites in the human genome while an elective genomic test analyzes the entire human genome. Some elective genetic and genomic tests require a physician to order the test to ensure that individuals understand the risks and benefits of testing as well as the results. Other DNA-based tests, such as a genealogical DNA test do not require a physician's order. Elective testing is generally not paid for by health insurance companies. With the advent of personalized medicine, also called precision medicine, an increasing number of individuals are undertaking elective genetic and genomic testing.

Clinical metagenomic next-generation sequencing (mNGS) is the comprehensive analysis of microbial and host genetic material in clinical samples from patients by next-generation sequencing. It uses the techniques of metagenomics to identify and characterize the genome of bacteria, fungi, parasites, and viruses without the need for a prior knowledge of a specific pathogen directly from clinical specimens. The capacity to detect all the potential pathogens in a sample makes metagenomic next generation sequencing a potent tool in the diagnosis of infectious disease especially when other more directed assays, such as PCR, fail. Its limitations include clinical utility, laboratory validity, sense and sensitivity, cost and regulatory considerations.

Personalized genomics is the human genetics-derived study of analyzing and interpreting individualized genetic information by genome sequencing to identify genetic variations compared to the library of known sequences. International genetics communities have spared no effort from the past and have gradually cooperated to prosecute research projects to determine DNA sequences of the human genome using DNA sequencing techniques. The methods that are the most commonly used are whole exome sequencing and whole genome sequencing. Both approaches are used to identify genetic variations. Genome sequencing became more cost-effective over time, and made it applicable in the medical field, allowing scientists to understand which genes are attributed to specific diseases.

Precision diagnostics is a branch of precision medicine that involves managing a patient's healthcare model and diagnosing specific diseases based on omics data analytics.

References

  1. ↑ "Department of Medicine - Stanford Medicine".
  2. ↑ "Oxford Education Deanery".
  3. ↑ "Leadership | Department of Medicine | Stanford Medicine". Stanford Medicine.
  4. ↑ "Family Heart Center | Stanford Center for Inherited Cardiovascular Disease | Stanford Medicine". Stanford Medicine.
  5. ↑ "Stanford Center for Inherited Cardiovascular Disease | Stanford Health Care". Stanford Health Care.
  6. ↑ "Heidi Salisbury". Preventive Cardiovascular Nurses Association.
  7. ↑ "Mark Zuckerberg Just Ran a Surprisingly Fast 5K". Runner's World. May 2023.
  8. ↑ "Victoria Parikh". Stanford Medicine.
  9. 1 2 Ashley, Euan A; Butte, Atul J; Wheeler, Matthew T; Chen, Rong; Klein, Teri E; Dewey, Frederick E; Dudley, Joel T; Ormond, Kelly E; Pavlovic, Aleksandra (1 January 2010). "Clinical assessment incorporating a personal genome". The Lancet. 375 (9725): 1525–1535. doi:10.1016/s0140-6736(10)60452-7. PMC   2937184 . PMID   20435227.
  10. ↑ Dewey, Frederick E.; Chen, Rong; Cordero, Sergio P.; Ormond, Kelly E.; Caleshu, Colleen; Karczewski, Konrad J.; Whirl-Carrillo, Michelle; Wheeler, Matthew T.; Dudley, Joel T. (15 September 2011). "Phased Whole-Genome Genetic Risk in a Family Quartet Using a Major Allele Reference Sequence". PLOS Genet. 7 (9): e1002280. doi: 10.1371/journal.pgen.1002280 . PMC   3174201 . PMID   21935354.
  11. ↑ Dewey, FE; Grove, ME; Pan, C; Goldstein, BA; Bernstein, JA; Chaib, H; Merker, JD; Goldfeder, RL; Enns, GM; David, SP; Pakdaman, N; Ormond, KE; Caleshu, C; Kingham, K; Klein, TE; Whirl-Carrillo, M; Sakamoto, K; Wheeler, MT; Butte, AJ; Ford, JM; Boxer, L; Ioannidis, JP; Yeung, AC; Altman, RB; Assimes, TL; Snyder, M; Ashley, EA; Quertermous, T (12 March 2014). "Clinical interpretation and implications of whole-genome sequencing". JAMA. 311 (10): 1035–1045. doi:10.1001/jama.2014.1717. ISSN   0098-7484. PMC   4119063 . PMID   24618965.
  12. ↑ Ashley EA (2016). "Towards precision medicine". Nat Rev Genet. 17 (9): 507–22. doi:10.1038/nrg.2016.86. PMID   27528417. S2CID   2609065.
  13. ↑ Dewey, Frederick E.; Wheeler, Matthew T.; Cordero, Sergio; Perez, Marco V.; Pavlovic, Aleks; Pushkarev, Dmitry; Freeman, James V.; Quake, Steve R.; Ashley, Euan A. (5 April 2011). "Molecular Autopsy for Sudden Cardiac Death Using Whole Genome Sequencing". Journal of the American College of Cardiology. 57 (14, Supplement): E1159. doi:10.1016/S0735-1097(11)61159-5.
  14. ↑ Dewey, Frederick E.; Chen, Rong; Cordero, Sergio P.; Ormond, Kelly E.; Caleshu, Colleen; Karczewski, Konrad J.; Whirl-Carrillo, Michelle; Wheeler, Matthew T.; Dudley, Joel T.; Byrnes, Jake K.; Cornejo, Omar E.; Knowles, Joshua W.; Woon, Mark; Sangkuhl, Katrin; Gong, Li; Thorn, Caroline F.; Hebert, Joan M.; Capriotti, Emidio; David, Sean P.; Pavlovic, Aleksandra; West, Anne; Thakuria, Joseph V.; Ball, Madeleine P.; Zaranek, Alexander W.; Rehm, Heidi L.; Church, George M.; West, John S.; Bustamante, Carlos D.; Snyder, Michael; Altman, Russ B.; Klein, Teri E.; Butte, Atul J.; Ashley, Euan A. (15 September 2011). "Phased Whole-Genome Genetic Risk in a Family Quartet Using a Major Allele Reference Sequence". PLOS Genetics. 7 (9): e1002280. doi: 10.1371/journal.pgen.1002280 . PMC   3174201 . PMID   21935354.
  15. ↑ Gahl, William A.; Wise, Anastasia L.; Ashley, Euan A. (2015). "The Undiagnosed Diseases Network of the National Institutes of Health". JAMA. 314 (17): 1797–8. doi:10.1001/jama.2015.12249. ISSN   0098-7484. PMID   26375289.
  16. ↑ Splinter K, Adams DR, Bacino CA, Bellen HJ, Bernstein JA, Cheatle-Jarvela AM, et al. (2018). "Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease". N Engl J Med. 379 (22): 2131–2139. doi:10.1056/NEJMoa1714458. PMC   6481166 . PMID   30304647.
  17. ↑ Gorzynski, John E. et al. 2022. “Ultrarapid Nanopore Genome Sequencing in a Critical Care Setting.” The New England Journal of Medicine, January. https://doi.org/10.1056/NEJMc2112090.
  18. ↑ "Fastest DNA sequencing technique helps undiagnosed patients find answers in mere hours". 11 February 2021.
  19. ↑ "Fastest Genome Sequencing with Dr. Euan Ashley".
  20. ↑ ""A new frontier": Fastest ever DNA sequencing technique achieved".
  21. ↑ "Three Stanford scholars awarded Guggenheim Fellowships". Stanford Report. Retrieved 7 April 2023.
  22. ↑ "Euan Angus Ashley - John Simon Guggenheim Memorial Foundation..." John Simon Guggenheim Memorial Foundation.
  23. ↑ "CAP Profile - Euan A. Ashley".
  24. ↑ Ashley, Euan A.; Ashley, Euan; Niebauer, Josef (3 December 2023). Cardiology Explained. Remedica. ISBN   978-1901346220.
  25. ↑ "The Genome Odyssey by Dr. Euan Angus Ashley". 14 October 2020.
  26. ↑ "EUAN ANGUS ASHLEY". euanangusashley.com.
  27. ↑ McClurg, Lesley. "Medical Detectives: The Last Hope For Families Coping With Rare Diseases", NPR , San Francisco, 17 December 2018. Retrieved on 28 January 2019.
  28. ↑ Kolata, Gina. "When the Illness Is a Mystery, Patients Turn to These Detectives", The New York Times , New York, 7 January 2019. Retrieved on 28 January 2019.
  29. ↑ "Company - Personalis".
  30. ↑ "Deepcell".
  31. ↑ "Silicon Valley Exercise Analytics (SVEXA)".
  32. ↑ "Leadership - Our Company - AstraZeneca". www.astrazeneca.com. Retrieved 17 May 2022.
  33. ↑ "Radcliffe Orchestra".
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