Annette Herscovics

Early Life

Annette Herscovics (née Nejman) was the daughter of Gersz Nejman (1906–1942) and Fradja Ruchla Lewi (1910–1959). She and her family were living in Paris when the Second World War broke out in the fall of 1939. By 1942, her father was sent first to the French Drancy transit camp and then to Auschwitz. Being the child of Polish immigrants of Jewish descent, she became one of the hidden children who survived Nazi-occupied Vichy France.

For years, Fradja and Annette escaped the grips of the Nazis by constantly moving. They narrowly escaped the rounding up of Jews in the infamous “La rafle du Vel' d'Hiv” by Parisian police in 1942. Their last safe haven was in the forests of Marcilhac-sur-Célé in southwestern France, a known resistance stronghold. During that time, mother and daughter were known as Andrée and Annette Bourdias. After the war, they returned to Paris in hopes of finding the family patriarch. They did not.

Annette’s mother remarried in 1951 to Leon Gelbert. Around that time, Annette, her mother and stepfather immigrated to Montreal, Canada.

Education and Early Career

Having begun her education in Paris, Annette Herscovics entered Outremont’s Strathcona Academy, where she obtained top-level marks. She was the top female student in the Quebec matriculation exam of her graduating year. It was also during this time she developed her love and talent for playing the violin. This talent was to carry her through her life.

Annette Herscovics then entered McGill University to continue her studies. At McGill she began her journey in the field of biochemistry and subsequently earned a Bachelor of Science in 1959. In 1960, she was awarded a $1,500 a-year fellowship by Union Carbide Canada Limited, which allowed her to continue pursuing her passion for fundamental basic research of cancer cell metabolism. She successfully obtained her PhD in biochemistry in 1963 under the supervision of Rose Johnstone at the McGill–Montreal General Hospital Research Institute. This was followed by being appointed as a lecturer (1967–1969) then assistant professor (1969–1971) in the world-renowned Department of Anatomy under the direction of Charles P. Leblond.

In 1971, Annette Herscovics moved to the Department of Biological Chemistry and Medicine at the Harvard Medical School in Boston. There, she became a research associate in the laboratory of Roger W. Jeanloz and was also appointed assistant professor.

In 1981, she returned to McGill University where she became an associate professor in the McGill Cancer Centre. By 1987, she was appointed full professor in the McGill Cancer Centre and the Department of Biochemistry and in 1992 in the Department of Oncology.

Key Discoveries

Did you know?
Sugars added to proteins are the most abundant protein modification in all cells of our body. These modifications are essential to life.

In 1969, Annette Herscovics published a paper on her discovery that sugar addition onto proteins occurred by molecular machines in two different compartments (organelles) in our cells, namely the endoplasmic reticulum and Golgi apparatus.

Annette Herscovics was able to follow the intricate path of formation of a model glycoprotein — thyroglobulin — using radioactive tracer molecules. Her breakthrough studies showed where in the cell the major protein of the thyroid gland gains its sugar modifications.

At the time, the endoplasmic reticulum was known as the site of synthesis of thyroglobulin. However, that the Golgi was an additional site of addition of sugars onto proteins was astonishing. Her discovery was followed by direct visualization studies showing at the light and electron microscopic levels the sites of sugar addition onto thyroglobulin first in the endoplasmic reticulum, then the Golgi apparatus. Her work demonstrated that glycosylation was a function of the Golgi as well as that of the endoplasmic reticulum.

Her next discovery at Harvard focused on her finding of sugar addition to newly synthesized proteins in the endoplasmic reticulum. She unravelled how sugars were first linked to an enormous fatty molecule known as a dolicholipid prior to flipping from the cell cytoplasm into the endoplasmic reticulum. It is this dolichol intermediate that then enables the sugar to be added to a newly synthesized protein inside the endoplasmic reticulum.

Returning to McGill University, Herscovics discovered the key enzymes in the endoplasmic reticulum and Golgi that then remove and add sugars to sculpt the glycoprotein for its maturation and function to be realized.

Herscovics also co-discovered a novel enzyme called “EDEM,” which can recognize newly synthesized sugar modified proteins that are aberrant and could cause disease. EDEM is involved in the selection and delivery of misfolded proteins in the endoplasmic reticulum for their elimination by degradation.

Did you know?
Glycoproteins are key proteins essential to many biological processes of life. Alterations of glycoproteins can be indicative of the presence of cancer.

Herscovics’s breakthrough studies led to our understanding of how glycoproteins are processed in all cells. Her pioneering legacy established the importance of the new field of glycobiology dedicated to the study of the array of sugars on proteins that cover enveloped viruses, bacteria, and all taxa in biology from yeast to plants to humans.

Legacy

Much like her former supervisor, Rose Johnstone, Annette was a trailblazer for women in science and academia. Both attended the Breaking the Barriers — A Women’s Action Conference at McGill University in 1990. This conference outlined solutions to navigate the hurdles women face at all levels in the university setting.

Annette Herscovics made significant contributions in the administration and direction of scientific research both in Canada and internationally throughout her career. She contributed to various research committees, including the U.S. Public Health Service at the NIH and National Cancer Institute of Canada. Her activities as Chair of the Graduate Advisory Committee at McGill University as well as the Fellowship Awards Committee attested to her commitment and interest in the future of Canadian science.

During her career, Annette Herscovics published over 110 peer-reviewed articles. She was made a Fellow of the Royal Society of Canada in 1998.

As a violinist, she was a member of McGill University’s I Medici di McGill Orchestra. The musicians of medical backgrounds perform public and benefit concerts as well as play for patients.

Annette Herscovics died of cancer in 2008. A memorial concert with music played by I Medici di McGill Quartet was held on 17 October 2008 in her honour.

Honours and Awards

• Continual funding with undergraduate scholarships and graduate fellowships, McGill University (1955–1962)
• Damon Runyon Memorial Fund (1962–1963)
• Fraser Monat Associateship, McGill University (1982–1988)
• Member of Pathobiochemistry Study Section, NIH (1985–1989)
• Member of the Editorial Board of the Journal of Biological Chemistry (1984–1989)
• Member of the Editorial Board of the journal Glycobiology (1990)
• Member of the Society for Glycobiology
• Member of the Board of Directors of the Canadian Biochemical Society (1989–1992)
• Bourse de perfectionnement pour recherche autonome, FRSQ (1990–1991)
• Member of the Council for the Society for Complex Carbohydrates (1993–1995)
• Member, Sous-commission BBC – La Commission des universités sur les Programme, Canada (1998–1999).
• Fellow, Royal Society of Canada (1998)
• Chair of Gordon Research Conference – Glycobiology (1999)

Key Terms

Organelles: Organelles are membrane-bound structures in all our cells. Each organelle has a specific function in the production of proteins, carbohydrates and lipids.

Endoplasmic reticulum: An organelle that is responsible for the synthesis and maturation of nascent proteins and lipids and storage of calcium. Here, chaperone proteins in the endoplasmic reticulum monitor their correct folding pattern, thereby ensuring the function of the new molecules.

Golgi apparatus: An organelle that is responsible for the transport, modification and packaging of molecules synthesized in the endoplasmic reticulum.

Glycoprotein: A glycoprotein is a protein with a covalently attached carbohydrate called a glycan. The addition of the glycan, known as “glycosylation,” occurs during post-translational modification of the nascent polypeptide in the endoplasmic reticulum and Golgi apparatus.