Carola Garcia de Vinuesa

Last updated

Professor
Carola Garcia de Vinuesa
FRS FAA FAHMS
Born1969 (age 54–55)
Spain
Alma mater Autonomous University of Madrid
University of Birmingham
Known for Immunogenetics
Scientific career
Fields Immunology
Institutions Francis Crick Institute

Australian Academy of Health and Medical Sciences

Australian Academy of Science

Carola Garcia de Vinuesa (born 1969) [1] is a Spanish doctor, scientist, and professor. She is Royal Society Wolfson Fellow and Senior Group Leader at the Francis Crick Institute in London, and at the John Curtin School of Medical Research in Canberra. She is a winner of the Australian Science Minister's Prize for Life Scientist of the Year and the Gottschalk Medal.

Contents

Education and career

Vinuesa obtained a Bachelor of Medicine at the Autonomous University of Madrid. [2]

While she was a student, she worked in a leprosy clinic in Kolkata on the shores of the Ganges, and helped train health workers in Ghana in rural areas. She said that Ghanan children were overwhelmingly admitted for unpreventable meningitis, leading her to believe that her time would be better spent learning the cause of the deadly disease, to develop preventative measures. She moved to the United Kingdom (UK) to do clinical training and doctoral research investigating the biological mechanisms of meningitis. [2] [3]

She was awarded a Doctor of Philosophy (PhD) in Immunology by the University of Birmingham in 2000. [2]

She received a Wellcome Trust International Travelling Fellowship in 2001 to undertake postdoctoral research at The John Curtin School for Medical Research at the Australian National University. [2]

In 2005, she discovered a genetic variant in mice that led to an auto-immune disease. [3] [4]

In 2014, Vinuesa was awarded a grant, [3] and that April, [5] opened The Centre for Personalised Immunology at ANU. She was one of the first people in Australia to use genomic sequencing to link diseases to genetic variation. [3]

In 2015, she was elected as a Fellow of the Australian Academy of Science. [6]

In October 2020, she became a Fellow of the Australian Academy of Health and Medical Sciences. [7]

In September 2021, the Lupus Research Alliance granted one of two of its $3 Million Global Team Science Awards to Vinuesa's team, led by Dr. Virginia Pascual, to examine why lupus differs from patient to patient. [8]

In 2022, Vinuesa relocated to the UK to take a new position at Francis Crick Institute. [3] [9]

CALM2 Variant and the Kathleen Folbigg Case (2018-present)

In August 2018, Vinuesa received a phone call from a former student who was concerned that Kathleen Folbigg may have been wrongfully convicted of infanticide. The student told her that the medical evidence presented at trial didn't "sit right" with several medical and legal experts, and thought Vinuesa's expertise in immunogenetics may help uncover an underlying disease that caused the Folbiggs' deaths. Vinuesa noted obvious signs of common causes for sudden infant death syndrome (SIDS), including floppy larynx and inflammation of the heart, that should have given reasonable doubt in the face of a lack of evidence of violence. Vinuesa agreed to consult on the case in an email to Folbigg's attorneys writing, "As a mother, I cannot think of a more worthy cause," and that she found it hard to believe someone could be imprisoned over it. [3]

In November 2018, Vinuesa and a colleague, geneticist Dr. Todor Arsov, sequenced Folbigg's DNA and analyzed it for genetic mutations that could be linked to diseases that could cause SIDS or Sudden Unexpected Death in Childhood (SUDC). [3] [10] They discovered a mutation on a gene named CALM2 (G114R), in a genetic family named Calmodulin (CALM) which had previously been associated with fatal cardiac arrhythmias such as long QT syndrome,and SUDC. A genetic simulation on CALM2 showed it was likely just as dangerous as the other variants. [3]

Hearings and testimony

The evidence presented in the reassessment of the New South Wales case was discounted as "speculation" by a team of scientists from Sydney commissioned by the Attorney General of Australia (AG). Dr. Michael Buckley, the Director of the Randwick Genomics Laboratory at the Prince of Wales Hospital, [11] argued that they should use the criteria set by the American College of Medical Genetics and Genomics for determining likelihood of pathogenicity, which requires 90% certainty to determine if disease is a likely cause. Vinuesa rejected this as she believed it was their role to determine whether or not there was reasonable doubt that Folbigg was guilty, not whether or not Folbigg, or her late infants, should have a definitive diagnosis. One of the researchers from the AG team, Dr. Matthew Cook, agreed with Vinuesa, splitting the experts into two groups to write two reports. [3]

During the reinvestigation, Vinuesa felt a lot of effort was placed to try and disqualify the experts on the side of the defence, rather than seeking the truth. Dr. Jonathan Skinner, who had gone over her medical files, testified that Folbigg had shown no signs of cardiac disease, and that it was not credible that Folbigg's children could have died from it. Arsov countered that Folbigg had recounted an incident of near-drowning when she was a teenager and had fainted while swimming in a pool, but a scientist on Buckley's team said her fainting may have been due to dehydration." [3] The Sydney team also argued that they were not aware of CALM mutations causing death while asleep in young children.

Conclusion and verdict

In 2019, following the conclusion of the hearings, Furness determined that nothing presented by Vinuesa's team had "clearly explained" the deaths of the infants. Vinuesa was disturbed by the prosecution's unwillingness to have doubt cast on the previous verdict and the lack of calmodulin experts at the hearings, and set out to find the opinions of the best recognised international experts. One of them, Prof. Peter Schwartz of Istituto Auxologico Italiano  [ it ], had just co-published a paper, Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry, [12] which contained information about a family with a nearly identical CALM variant (G114W) in which two children suffered a sudden cardiac arrest while the mother, who had been the carrier of the gene's mutation, was seemingly healthy. He concluded he had "significant doubts" about Folbigg's conviction, and that the accusation of infanticide may have been premature. [3]

Despite the CALM2 variant now qualifying as "likely pathogenic," Buckley's team and the prosecution seemed unwilling to accept the new evidence. Vinuesa dug into Schwartz's Registry and found that up to 20% of sudden cardiac deaths occur in sleep, and that there were nine reported cases of these types of deaths in infants and toddlers and wrote up a brief for the inquiry. [3] [12] [13]

In July 2019, the presiding judicial officer, Reginald Blanch, delivered his verdict that Folbigg would remain in prison, citing that he "preferred" the expertise and evidence of Buckley and Skinner, and excerpts from a diary which showed evidence of postpartum depression, which Vinuesa felt showed a woman "grappling with the occasional despair of motherhood." Vinuesa reflected on society's pressure on mothers and her own experience." [3]

Appeal

Vinuesa believed that the verdict was "deeply unjust," and continued her research into CALM2. She persuaded Danish biochemist, Michael Toft Overgard, to run tests on the mutation in a synthetic cell, resulting in unambiguous results that the CALM2 variant in Folbigg's DNA was not only arrythmogenic (i.e. “pathogenic” and therefore potentially lethal), but mirrored the results of other CALM variants known to cause death in young children while asleep. [3] [14] In 2020, Vinuesa, Arsov, Schwartz, and 24 other scientists co-authored a paper called, Infanticide vs. inherited cardiac arrhythmias, which was published that November by EP Europace. [15] Folbigg's legal team used the paper as evidence in an appeal to the Supreme Court of New South Wales, but the judges upheld Blanch's decision. [3]

Advocacy

In March 2021, Vinuesa, alongside more than 100 other scientists including two Nobel prize winners, signed a petition to grant Folbigg royal prerogative of mercy based on Vinuesa's research. The petition states that to keep Folbigg imprisoned sets a dangerous precedent that "cogent medical and scientific evidence can simply be ignored in preference to subjective interpretations and circumstantial evidence." [3] Vinuesa since visited Folbigg in prison.

Also in March 2021, Vinuesa wrote an essay for The Conversation casting doubt on the verdict and sharing evidence her and her team had presented during the appeal. She also criticized the judicial process itself, saying that her experience discouraged her from engaging in cases in the future. She warned that if her experience is common of scientific experts, the law is risking engagement from the scientific community in legal matters. She said that scientists should be chosen who base their reasoning on "peer-reviewed scientific evidence," with specific expertise on the fields in question, and needed to be "treated as equals" to and by their legal peers during the process. She said that she hopes in the coming years that legal settings will welcome and appreciate the scientific method. [16]

On June 5, 2023, as a result of the interventions of the scientific community, Kathleen Folbigg was granted an unconditional pardon and set free, pending the quashing of the 2003 verdict.

Awards and recognition

She was the 2008 winner of the Australian Science Minister's Prize for Life Scientist of the Year [17] and the 2009 winner of the Australian Academy of Science's Gottschalk Medal for her research uncovering the origins of autoimmune diseases. [18] In 2022 Vinuesa was elected a Fellow of the Royal Society. [19]

Personal life

Vinuesa was born and raised in Cadiz, Spain. [1] [2] She has two daughters. Vinuesa says her career decisions echoed her father's, who was a community-servant lawyer. He worked in the second democratic government in Spain as a treasury inspector. [3]

As of August 2021, Vinuesa lives in the UK. [3]

https://www.crick.ac.uk/research/labs/carola-vinuesa

Related Research Articles

<span class="mw-page-title-main">Brugada syndrome</span> Heart conduction disease

Brugada syndrome (BrS) is a genetic disorder in which the electrical activity of the heart is abnormal due to channelopathy. It increases the risk of abnormal heart rhythms and sudden cardiac death. Those affected may have episodes of syncope. The abnormal heart rhythms seen in those with Brugada syndrome often occur at rest. They may be triggered by a fever.

<span class="mw-page-title-main">Long QT syndrome</span> Medical condition

Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting, drowning, seizures, or sudden death. These episodes can be triggered by exercise or stress. Some rare forms of LQTS are associated with other symptoms and signs including deafness and periods of muscle weakness.

<span class="mw-page-title-main">Arrhythmogenic cardiomyopathy</span> Medical condition

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease.

<span class="mw-page-title-main">Dilated cardiomyopathy</span> Condition involving an enlarged, ineffective heart

Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Complications can include heart failure, heart valve disease, or an irregular heartbeat.

<span class="mw-page-title-main">Short QT syndrome</span> Medical condition

Short QT syndrome (SQT) is a very rare genetic disease of the electrical system of the heart, and is associated with an increased risk of abnormal heart rhythms and sudden cardiac death. The syndrome gets its name from a characteristic feature seen on an electrocardiogram (ECG) – a shortening of the QT interval. It is caused by mutations in genes encoding ion channels that shorten the cardiac action potential, and appears to be inherited in an autosomal dominant pattern. The condition is diagnosed using a 12-lead ECG. Short QT syndrome can be treated using an implantable cardioverter-defibrillator or medications including quinidine. Short QT syndrome was first described in 2000, and the first genetic mutation associated with the condition was identified in 2004.

<span class="mw-page-title-main">Jervell and Lange-Nielsen syndrome</span> Medical condition

Jervell and Lange-Nielsen syndrome (JLNS) is a rare type of long QT syndrome associated with severe, bilateral sensorineural hearing loss. Those with JLNS are at risk of abnormal heart rhythms called arrhythmias, which can lead to fainting, seizures, or sudden death. JLNS, like other forms of long QT syndrome, causes the cardiac muscle to take longer than usual to recharge between beats. It is caused by genetic variants responsible for producing ion channels that carry transport potassium out of cells. The condition is usually diagnosed using an electrocardiogram, but genetic testing can also be used. Treatment includes lifestyle measures, beta blockers, and implantation of a defibrillator in some cases. It was first described by Anton Jervell and Fred Lange-Nielsen in 1957.

<span class="mw-page-title-main">Romano–Ward syndrome</span> Medical condition

Romano–Ward syndrome is the most common form of congenital Long QT syndrome (LQTS), a genetic heart condition that affects the electrical properties of heart muscle cells. Those affected are at risk of abnormal heart rhythms which can lead to fainting, seizures, or sudden death. Romano–Ward syndrome can be distinguished clinically from other forms of inherited LQTS as it affects only the electrical properties of the heart, while other forms of LQTS can also affect other parts of the body.

<span class="mw-page-title-main">Andersen–Tawil syndrome</span> Rare autosomal dominant genetic disorder

Andersen–Tawil syndrome, also called Andersen syndrome and long QT syndrome 7, is a rare genetic disorder affecting several parts of the body. The three predominant features of Andersen–Tawil syndrome include disturbances of the electrical function of the heart characterised by an abnormality seen on an electrocardiogram and a tendency to abnormal heart rhythms, physical characteristics including low-set ears and a small lower jaw, and intermittent periods of muscle weakness known as hypokalaemic periodic paralysis.

SCN5A Protein-coding gene in the species Homo sapiens

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Kathleen Megan Folbigg is an Australian woman who was wrongfully convicted in 2003 of murdering her four infant children. She was pardoned in 2023 after 20 years in jail following a long campaign for justice by her supporters, and had her convictions overturned on appeal a few months later.

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<span class="mw-page-title-main">Calmodulin 1</span> Protein found in humans

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<span class="mw-page-title-main">CALM2</span> Protein-coding gene in humans

Calmodulin 2 is a protein that in humans is encoded by the CALM2 gene. A member of the calmodulin family of signaling molecules, it is an intermediary between calcium ions, which act as a second messenger, and many intracellular processes, such as the contraction of cardiac muscle.

<span class="mw-page-title-main">Ankyrin-2</span> Protein-coding gene in the species Homo sapiens

Ankyrin-2, also known as Ankyrin-B, and Brain ankyrin, is a protein which in humans is encoded by the ANK2 gene. Ankyrin-2 is ubiquitously expressed, but shows high expression in cardiac muscle. Ankyrin-2 plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in cardiomyocytes, as well as in costamere structures. Mutations in ANK2 cause a dominantly-inherited, cardiac arrhythmia syndrome known as long QT syndrome 4 as well as sick sinus syndrome; mutations have also been associated to a lesser degree with hypertrophic cardiomyopathy. Alterations in ankyrin-2 expression levels are observed in human heart failure.

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References

  1. 1 2 Australia's Nobel laureates : adventures in innovation. John Keeney (2nd ed.). Roseville, N.S.W.: ETN Communications. 2011. p. 146. ISBN   978-0-9775866-7-7. OCLC   792987113.{{cite book}}: CS1 maint: others (link)
  2. 1 2 3 4 5 Director (Research Services Division). "Professor Carola Garcia de Vinuesa". researchers.anu.edu.au. Retrieved 25 July 2019.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Schwartz, Oscar (9 December 2021). "4 Dead Infants, a Convicted Mother, and a Genetic Mystery". Wired . Retrieved 23 January 2022.
  4. ↑ Vinuesa, Carola G.; Cook, Matthew C.; Angelucci, Constanza; Athanasopoulos, Vicki; Rui, Lixin; Hill, Kim M.; Yu, Di; Domaschenz, Heather; Whittle, Belinda; Lambe, Teresa; Roberts, Ian S. (26 May 2005). "A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity". Nature. 435 (7041): 452–458. Bibcode:2005Natur.435..452V. doi:10.1038/nature03555. ISSN   1476-4687. PMID   15917799. S2CID   4413889.
  5. ↑ "The Centre for Personalised Immunology". Australian National University . Retrieved 23 January 2022.
  6. ↑ "Carola Vinuesa". www.science.org.au. Retrieved 25 July 2019.
  7. ↑ "Academy elects 28 new Fellows". AAHMS - Australian Academy of Health and Medical Sciences. 14 October 2020. Retrieved 7 December 2020.
  8. ↑ Alliance, Lupus Research. "Lupus Research Alliance Grants $6 Million in First Global Team Science Awards". www.prnewswire.com. Retrieved 23 January 2022.
  9. ↑ McKie, Robin (9 January 2022). "Global spread of autoimmune disease blamed on western diet". The Guardian . Retrieved 10 February 2022.
  10. ↑ "Scientists call for Kathleen Folbigg's release, saying children likely died of natural causes". The Guardian . 4 March 2021. Retrieved 23 January 2022.
  11. ↑ "Randwick Genomics Laboratory, Prince of Wales Hospital - Labs - GTR - NCBI". www.ncbi.nlm.nih.gov. Retrieved 23 January 2022.
  12. 1 2 Crotti, Lia; Spazzolini, Carla; Tester, David J.; Ghidoni, Alice; Baruteau, Alban-Elouen; Beckmann, Britt-Maria; Behr, Elijah R.; Bennett, Jeffrey S.; Bezzina, Connie R.; Bhuiyan, Zahurul A.; Celiker, Alpay (14 September 2019). "Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry". European Heart Journal. 40 (35): 2964–2975. doi:10.1093/eurheartj/ehz311. ISSN   1522-9645. PMC   6748747 . PMID   31170290.
  13. ↑ Vinuesa, Carola G; Cook, Matthew (29 March 2019). "Initial Report into the Genetic Sequencing of the Folbigg Family" (PDF). Inquiry into the convictions of Kathleen Megan Folbigg.
  14. ↑ Whinnett, Ellen (6 March 2021). "How killer mum Folbigg's saliva swab led to genetic twist". Broome Advertiser. Australia . Retrieved 23 January 2022.
  15. ↑ Brohus, Malene; Arsov, Todor; Wallace, David A; Jensen, Helene Halkjær; Nyegaard, Mette; Crotti, Lia; Adamski, Marcin; Zhang, Yafei; Field, Matt A; Athanasopoulos, Vicki; Baró, Isabelle (1 March 2021). "Infanticide vs. inherited cardiac arrhythmias". EP Europace. 23 (3): 441–450. doi:10.1093/europace/euaa272. ISSN   1099-5129. PMC   7947592 . PMID   33200177.
  16. ↑ Vinuesa, Carola Garcia de. "Kathleen Folbigg's children likely died of natural causes, not murder. Here's the evidence my team found". The Conversation . Retrieved 23 January 2022.
  17. ↑ "Professor Carola Garcia de Vinuesa". Australian National University . Retrieved 13 August 2014.
  18. ↑ 2009 awardees, Australian Academy of Science, retrieved 23 March 2016.
  19. ↑ "Outstanding Academy Fellows elected to Royal Society". Australian Academy of Science. Retrieved 10 May 2022.
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