Peter St George-Hyslop

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Peter Henry St George-Hyslop, OC, FRS, FRSC, FRCPC, (born July 10, 1953) is a British and Canadian medical scientist, neurologist and molecular geneticist who is known for his research into neurodegenerative diseases. St George-Hyslop is one of the most cited authors in the field of Alzheimer's disease research. [1] He has identified a number of key genes that are responsible for nerve cell degeneration and early-onset forms of Alzheimer's disease. These include the discovery of the presenilins (PSEN1 and PSEN2) [2] , Nicastrin [3] , TREM2 [4] , Apolipoprotein E [5] and SORL1 [6] genes. Presenilin mutations are the most common cause of familial Alzheimer's disease. [7] St George-Hyslop also co-led the discovery of the gene for the amyloid precursor protein. [8]

St George-Hyslop's father, Noel St George Hyslop was a renowned scientist who worked on Foot and Mouth Disease virus.

Since 2007 St George-Hyslop has headed an Alzheimer's disease research program as Professor of Experimental Neuroscience at the University of Cambridge. [9] [10]

Educated at Wellington School, Wellington, Somerset, UK, St George-Hyslop completed his medical training in Canada, graduating with the MD degree in 1976, and then pursuing post-doctoral research in internal medicine and neurology at the University of Toronto and Harvard Medical School. He served his first appointment at Harvard's Massachusetts General Hospital, where he taught molecular genetics and neurology from 1987 to 1991. He was appointed to the University of Toronto in 1991, and since 2003 has held the university's highest rank of University Professor. From 1995 to 2018, St George-Hyslop served as the director of the Tanz Centre for Research in Neurodegenerative Diseases at the University of Toronto Faculty of Medicine. [11] [12] In 2007 St George-Hyslop was appointed Professor of Experimental Neuroscience at the University of Cambridge.

He was awarded the Metlife Foundation Award for Medical Research in Alzheimer's Disease in 1987, [13] the Howard Hughes Medical Institute International Scholar Award in 1997 and 2002, the Gold Medal in Medicine from the Royal College of Physicians of Canada in 1994, the Michael Smith Award from the Canadian Institutes of Health Research in 1997 and the Dan David Prize in 2014. [14] He is a member of the American Society for Clinical Investigation, a fellow of the Royal Society of London and the Royal Society of Canada, and a Foreign Member to the Institute of Medicine of the United States National Academies. He was appointed Officer of the Order of Canada in 2018. [15]

Related Research Articles

<span class="mw-page-title-main">Neurodegenerative disease</span> Central nervous system disease

A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic.Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.

The Alzheimer Society of Ontario (ASO) is a care and research charity committed to helping people living with Alzheimer's disease and other dementias by:

<span class="mw-page-title-main">Gamma secretase</span> Type of protein

Gamma secretase is a multi-subunit protease complex, an integral membrane protein, that cleaves single-pass transmembrane proteins at residues within the transmembrane domain. Proteases of this type are known as intramembrane proteases. The most well-known substrate of gamma secretase is amyloid precursor protein, a large integral membrane protein that, when cleaved by both gamma and beta secretase, produces a short 37-43 amino acid peptide called amyloid beta whose abnormally folded fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. Gamma secretase is also critical in the related processing of several other type I integral membrane proteins, such as Notch, ErbB4, E-cadherin, N-cadherin, ephrin-B2, or CD44.

<span class="mw-page-title-main">Presenilin</span>

Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified in screens for mutations causing early onset forms of familial Alzheimer's disease by Peter St George-Hyslop. Vertebrates have two presenilin genes, called PSEN1 that codes for presenilin 1 (PS-1) and PSEN2 that codes for presenilin 2 (PS-2). Both genes show conservation between species, with little difference between rat and human presenilins. The nematode worm C. elegans has two genes that resemble the presenilins and appear to be functionally similar, sel-12 and hop-1.

Christine Van Broeckhoven is a Belgian molecular biologist and professor in Molecular genetics at the University of Antwerp. She is also leading the VIB Department of Molecular Genetics, University of Antwerp of the Flanders Institute for Biotechnology (VIB). Christine Van Broeckhoven does research on Alzheimer dementia, bipolar mental disorders and other neurological diseases. Since 1983 she has had her own laboratory for molecular genetics at the University of Antwerp, and since 2005 is focussing her research on neurodegenerative brain diseases. She is an associate editor of the scientific journal Genes, Brain and Behavior.

<span class="mw-page-title-main">SORL1</span> Protein-coding gene in the species Homo sapiens

Sortilin-related receptor, L(DLR class) A repeats containing is a protein that in humans is encoded by the SORL1 gene.

<span class="mw-page-title-main">Nicastrin</span>

Nicastrin, also known as NCSTN, is a protein that in humans is encoded by the NCSTN gene.

<span class="mw-page-title-main">Presenilin-1</span> Protein-coding gene in the species Homo sapiens

Presenilin-1(PS-1) is a presenilin protein that in humans is encoded by the PSEN1 gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta (Aβ) from amyloid-beta precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease.

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

Presenilin-2 is a protein that is encoded by the PSEN2 gene.

Early-onset Alzheimer's disease (EOAD), also called younger-onset Alzheimer's disease (YOAD), is Alzheimer's disease diagnosed before the age of 65. It is an uncommon form of Alzheimer's, accounting for only 5–10% of all Alzheimer's cases. About 60% have a positive family history of Alzheimer's and 13% of them are inherited in an autosomal dominant manner. Most cases of early-onset Alzheimer's share the same traits as the "late-onset" form and are not caused by known genetic mutations. Little is understood about how it starts.

<span class="mw-page-title-main">Rudolph E. Tanzi</span> American geneticist

Rudolph Emile 'Rudy' Tanzi a professor of Neurology at Harvard University, vice-chair of neurology, director of the Genetics and Aging Research Unit, and co-director of the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital (MGH).

<span class="mw-page-title-main">Krembil Research Institute</span> Academic medical research institute in Toronto

The Krembil Research Institute, formerly known as the Toronto Western Research Institute, is an academic medical research institute in Toronto. It is one of the largest research institutes in Canada focusing on human neurological disease.

Alison Mary Goate is the Jean C. and James W. Crystal Professor and Chair of the Department of Genetics and Genomic Sciences and Director of the Loeb Center for Alzheimer's Disease at Icahn School of Medicine at Mount Sinai, New York City. She was previously professor of genetics in psychiatry, professor of genetics, and professor of neurology at Washington University School of Medicine.

Rosa Rademakers is a Dutch neurogeneticist and professor within the Department of Neuroscience at the Mayo Clinic. Her research centers on the genetic basis of neurodegenerative diseases, such as identifying causal genes and their function, exploring familial risk factors, and the mechanism of the degeneration. Her neurodegenerative diseases of focus include "Alzheimer's disease (AD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS)." She received a Bachelor of Arts in Biology, a Master of Arts in Biochemistry, and a Ph.D. in Science, all from the University of Antwerp. Originally from the Netherlands, she came to the Mayo Clinic in 2005 for a post-doctoral fellowship, and in 2007 she was given a lab director position.

Carlos Cruchaga is a human genomicist with expertise in multi-omics, informatics, and neurodegeneration, with a focus on Alzheimer's and Parkinson's Disease. He is a Professor of Psychiatry, Neurology and Genetics and Washington University School of Medicine. He is founding director of the Neurogenomics and Informatic (NGI) center at Washington University School of Medicine.

<span class="mw-page-title-main">Martin Rossor</span>

Martin Neil Rossor, is a British clinical neurologist with a specialty interest in degenerative dementias and familial disease.

Dennis J. Selkoe is an American physician (neurologist) known for his research into the molecular basis of Alzheimer's disease. In 1985 he became Co-Director of the Center for Neurological Diseases and from 1990, Vincent and Stella Coates Professor of Neurological Diseases at Harvard Medical School. He is also a Fellow of the AAAS and a member of the National Academy of Medicine.

Gerard David Schellenberg is an academic neuropathologist who specializes in the research of Alzheimer's disease. He is the director of Penn Neurodegeneration Genomics Center as well as a professor of Pathology and Laboratory Medicine at the University of Pennsylvania. He is a leading contributor to Alzheimer's disease research.

James Affram Adjaye is a Ghanaian British Stem cell scientist. He is the Director of the Institute for Stem Cell Research and Regenerative Medicine at the Heinrich Heine University's faculty of medicine. He also led the Molecular Embryology and Aging Group of the Max Planck Institute for Molecular Genetics situated in Berlin, Germany.

Alzheimer's disease (AD) in the Hispanic/Latino population is becoming a topic of interest in AD research as Hispanics and Latinos are disproportionately affected by Alzheimer's Disease and underrepresented in clinical research. AD is a neurodegenerative disease, characterized by the presence of amyloid-beta plaques and neurofibrillary tangles, that causes memory loss and cognitive decline in its patients. However, pathology and symptoms have been shown to manifest differently in Hispanic/Latinos, as different neuroinflammatory markers are expressed and cognitive decline is more pronounced. Additionally, there is a large genetic component of AD, with mutations in the amyloid precursor protein (APP), Apolipoprotein E APOE), presenilin 1 (PSEN1), bridging Integrator 1 (BIN1), SORL1, and Clusterin (CLU) genes increasing one's risk to develop the condition. However, research has shown these high-risk genes have a different effect on Hispanics and Latinos then they do in other racial and ethnic groups. Additionally, this population experiences higher rates of comorbidities, that increase their risk of developing AD. Hispanics and Latinos also face socioeconomic and cultural factors, such as low income and a language barrier, that affect their ability to engage in clinical trials and receive proper care.

References

  1. "Science.ca : Peter Henry St. George-Hyslop".
  2. "Cloning of a novel gene bearing missense mutations in early onset familial Alzheimer Disease". Nature.
  3. "Nicastrin modulates presenilin-mediated Notch/Gip1 signal transduction and bAPP processing". Nature.
  4. "TREM2 variants in Alzheimer's disease". New England Journal of Medicine. PMC   3631573 .
  5. "Association of Apoliprotein E allele e4 with the late-onset familial and sporadic Alzheimer Disease". Neurology.
  6. "The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer's Disease". Nature Genetics. PMC   2657343 .
  7. "Presenilin mutations and their impact on neuronal differentiation in Alzheimer's disease". Neural Regeneration Research. PMID   34100423.
  8. "A Hundred Years of Alzheimer's Disease Research". Neuron. PMID   17015223.
  9. "Horizons magazine". 19 February 2013.
  10. "Prof Peter St George-Hyslop". www.cimr.cam.ac.uk. Archived from the original on 2007-11-09.
  11. "About the Centre | Tanz Centre for Research in Neurodegenerative Diseases".
  12. "Director's Message | Tanz Centre for Research in Neurodegenerative Diseases". tanz.med.utoronto.ca.
  13. "MetLife Foundation Awards for Medical Research in Alzheimer's Disease" (PDF). Archived from the original (PDF) on 13 October 2018.
  14. "Dan David Foundation announces winners of prize". The Jerusalem Post | JPost.com. 11 February 2014. Retrieved 2020-11-02.
  15. "Order of Canada Appointments". 29 June 2018. Archived from the original on 29 September 2020. Retrieved 18 February 2019.

Further reading