20 September 1929 - 8 Aug 2013
b. Timmins, ON
Senior Emeritus Scientist at the Hospital for Sick Children
BA (physiology, biochemistry) UofT, MD (UofT), PhD in biochemistry (UofT)
A Tribute to Dr. Mario Moscarello (1929 – 2013)
1Research Institute, Hospital for Sick Children, PGCRL, Toronto, ON, M5G 0A4, Canada. E-mail:
2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto,
Ontario, M5S 1A8, Canada. E-mail: email@example.com.
3Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, N1G
2W1, Canada. E-mail: firstname.lastname@example.org.
Dr. Mario Antonio Moscarello (20 September 1929 – 8 August 2013)
Dr. Mario Moscarello passed away on August 8, 2013 at the age of 83 years with his family by
his side. Mario was a pioneer in myelin research and in the role of myelin instability in the cause
and severity of Multiple Sclerosis (MS).
Mario was born in Timmins, Ontario, in 1929. He obtained three degrees from the University of
Toronto – B.A. (Physiology and Biochemistry, 1951), Medicine (1955), and Ph.D. (Biochemistry,
under the supervision of Professor Charles Hanes, 1961). Mario received an MRC Fellowship to
carry out post-doctoral work under Professor Lou Siminovitch at the Ontario Cancer Institute
(1962-1964). In 1964, he joined the Biochemistry Department at the Research Institute of
the Hospital for Sick Children under the leadership of Dr. Sandy Jackson. He served as a staff
member at the hospital until his death.
In 2005, Mario lost Rebeka (Reva, nee Sheinin), his wife of many years. At his death, he left a
son (Raphael), a daughter (Carmen), and 4 grandchildren (Tia, Dominic, Matthew, and Nathan).
During the first 8 years of their marriage, both Reva and Mario were at various stages of their
medical training, and handled their various career and family roles interchangeably. Even in
those early years on a shoe-string budget, the famed Moscarello culinary brilliance was in full
force. Together, Reva and Mario produced countless delicious meals. In time, Reva received an
F.R.C.P. in Psychiatry, and Mario completed his Ph.D. and Post-Doctoral Fellowship.
Wine was, of course, one of Mario’s great delights, both as a producer and as an expert
consumer. For many years Mario bought Zinfandel grapes imported from California and, with
a wine press in his basement, converted them into a superb red wine in sufficient quantities to
last him for a year. Wine-making became a famous Moscarello “HOLY Annual Ritual”. Another
Mario love was ice hockey, and he was instrumental in creating the infamous Sick Children’s
Hospital hockey team. In fact, he was a superb athlete – tall and long-legged, a champion
runner in his youth, and a formidable competitor in squash during his long years at Sick Kids.
In 1971, Mario was appointed as an Assistant Professor in the Department of Biochemistry
at the University of Toronto. This was the first “town-gown” cross-appointment from the
Hospital to the University. He became a Full Professor at the University in 1980, and was
cross-appointed to the Department of Laboratory Medicine and Pathobiology in 1982. After
retirement in 1994 at the age of 65, Mario remained in the laboratory as a Professor Emeritus
at the University, and a Senior Scientist Emeritus at the Hospital. In his long Curriculum vitae,
Mario’s scientific rigour is illustrated by the successful post-doctoral fellows and graduate
students that he trained, 51 in total, as well as the 280 publications and 7 book chapters that he
Mario understood the give and take necessary to forge new paths in science; however, he
played to win. Never one to hold back his opinions, he gave it to you straight in agreement or
opposition. Mario promoted “extra-curricular” activities with his trainees as he believed that if
you played together well, then collaboration in the laboratory would readily follow. His intellect
was not only apparent in his science but also in his sense of humour and fondness for pranks.
His infamous office door was the site of friendly pictorial banter regarding any subject from
heritage to sport.
Mario exhibited tireless energy as a research scientist, giving time to journals and grant review
panels such as the MS Society of Canada. The latter funded his research throughout his career.
Mario also served the Hospital in several other capacities over the years. In 1965, Mario
initiated the “internal grant review” process, a first in any Canadian institution. This review
process is still mandatory for all scientists at the Hospital for Sick Children’s Research Institute.
For many years Mario was also a partner in a successful Medical Laboratory Services company.
As Chairman of the Hospital’s Equipment Committee (1977-1995), Mario’s business experience
ensured that the Hospital obtained the best value for its money from all its many suppliers of
materials and equipment.
Mario played a key role in the drive to bring strength in basic science to the pursuit of improved
child health at the Hospital. He believed a strong foundation in the basics would naturally lead
to understanding and treatments of childhood diseases. His critical insights and background
in both medical and basic science were essential to this success. Mario’s research program
focussed on demyelinating diseases, particularly MS, assimilating the underlying structural
biochemistry of the myelin sheath with mechanisms elucidated to participate in myelin
His early career involved active research in the biochemistry of amino acids in
encephalomyelitis and the encephalomyocarditis virus. This foundation, both in amino acid
analyses and myelin changes, prepared him for his subsequent transition to studies of a
newly-discovered encephalitogenic determinant isolated from myelin, which we now know
as myelin basic protein (MBP). In 1971, he discovered that MBP fractions contained a non- coded amino acid – citrulline. This study was coincident with G. E. Rogers’s isolation of citrulline
as a component of proteins from cells in hair fibre medullae and inner root sheaths of hair
follicles, and was arguably one of the early milestones in the field of deimination (citrullination)
Over the next several decades, the spine of Mario’s research program was MBP, which he
considered the “executive” molecule of the myelin sheath. Mario posited early on that “a
primary defect in myelin basic protein is responsible for the initial changes in myelin in MS, and
precedes the autoimmune response”. He recognized that the severity of MS correlates with the
degree of deimination of myelin basic protein, and noted that, paradoxically, adult MS myelin
resembles normal childhood myelin. Like rheumatoid arthritis, MS could be considered in part a
“post-translational disease”, as this modification of MBP could explain many aspects of disease
pathogenesis, including the release of immunodominant epitopes.
Mario’s group established that up-regulation of an isozyme of peptidylarginine deiminase
(PAD2) was responsible for hyper-deimination not only of MBP, but also other glial proteins,
and could represent an early molecular event preceding the formation of MS lesions. Mario
believed that targeting this enzyme offered potential new avenues for therapy for MS patients,
and was passionate in his pursuit of this concept, using novel animal models to evaluate
PAD inhibitors. He pursued this passion almost until forced by illness to withdraw from the
laboratory a few months before his death.
To this day, we do not know the initial events in myelin that lead to demyelinating foci and
eventually to MS. Mario’s ideas in the 1970s were already prescient of present “inside- out” models of disease pathogenesis and the role of epigenetic mechanisms. The study of
protein deimination in a plethora of disorders is now a burgeoning discipline, and Mario’s
ground-breaking contributions have been recognized in an accolade published this year in
a book entitled "Protein deimination in human health and disease" (A.P. Nicholas and S.K.
Bhattacharya, eds., Springer, New York, Heidelberg, 2014).
Mario lived all aspects of his life on his terms and to the fullest. He will be greatly missed
by his family, friends, and scientific colleagues. In ending, we wish also to acknowledge his
long-standing colleague and friend, Dr. D. Denise Wood. Denise was the engine of Mario’s
laboratory, performing experiments, training new lab members and collaborators and
publishing with Mario for over 40 years. With Denise’s blessing, Mario would tell new students
that Denise’s first name was Deciduous – it was a test to see how quickly one could process
information. Many of us remain indebted to them both.