Moscarello, Mario

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20 September 1929 - 8 Aug 2013

b. Timmins, ON

Biochemistry / Laboratory Medicine and Pathobiology

Professor Emeritus

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)

Harry Schachter1

JoAnne McLaurin2

George Harauz3

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:

3Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, N1G

2W1, Canada. E-mail:


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.