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UTHSCSA
UNINTERRUPTED FUNDING
Dr. Casali’s groundbreaking work in human B cells and anti-
bodies in the 1980s and ‘90s was instrumental in the development
of the first human monoclonal antibodies that neutralize rabies
virus, as well as those that treat some autoimmune diseases. His
laboratory was one of the few in the world at the time that could
produce specifically targeted human monoclonal antibodies, and
contributed significantly to the creation of a human monoclonal
antibody to tumor necrosis factor alpha (TNF-α which was ap-
proved by the FDA as the drug adalimumab (brand name Hu-
mira®), an effective treatment which is now one of the most
popular drugs in the world. Adalimumab has been FDA ap-
proved for treatment of rheumatoid arthritis, psoriatic arthritis,
ankylosing spondylitis, Crohn’s disease, ulcerative colitis, moder-
ate to severe chronic psoriasis and juvenile idiopathic arthritis.
Dr. Casali’s research has been funded uninterruptedly by the
N.I.H. for almost three decades as well as by private founda-
tions. His work has been published in high-profile journals such
as Science, Nature Immunology, Immunity, Cell, Journal of Ex-
perimental Medicine and the Journal of Immunology. Since
2002, he has also served as editor-in-chief of Autoimmunity, an
international peer-reviewed journal that publishes clinical and
basic science articles on immunology, genetics and the molecular
biology of immunity and autoimmunity. Throughout his career
he has served as a member of many N.I.H. review panels and
study sections, and received many formal acknowledgements of
his scientific accomplishments.
His work on drugs termed epigenetic modulators is the basis
of a $600,000, three-year grant Dr. Casali received last year from
the Alliance for Lupus Research. Epigenetic modulators, often
used in the treatment of lymphomas, may turn out to be useful
therapies for lupus as well. Systemic lupus erythematosus (SLE)
is an autoimmune disease that debilitates approximately 1 million
people in the United States, mostly women in their fertile years.
Approximately 16,000 new cases are diagnosed each year.
In SLE patients, the immune responses typically attack the kid-
neys, lungs, heart, skin, brain and even the central nervous sys-
tem. It is a generalized attack that systematically destroys the inner
core of most cells of the body, including the DNA and other con-
stituents of the cellular nuclei. Dr. Casali has contributed to fun-
damental understandings about the immune system abnormalities
that occur in SLE. These findings provide a scientific rationale
for why epigenetic modulators might be effective in humans. In
addition, the Alliance for Lupus Research grant will identify novel
targets for new lupus therapeutics.
Dr. Casali’s strategy now is to dig even deeper, trying to under-
stand in precise detail more of how these processes work and how
they are modulated. This includes the identification of what are
DEAN’S MESSAGE
known as “HDAC” (histone deacetylase) inhibitors, such as the
naturally occurring butyrate, which is produced by gut flora and
modulates microRNAs, acting as an inhibitor to unwanted au-
toimmune response, suggesting that it is critical in the homeosta-
sis of the immune response.
FOCUS ON TWO ELEMENTS
Dr. Casali’s studies focus on two elements that are critical to
antibody production and differentiation in B cells. The first is
mediated by the enzyme activation-induced cytidine deaminase
(AID), which is critical for class-switch recombination and so-
matic hypermutation. The second is B lymphocyte-induced mat-
uration protein-1 (Blimp-1), which is required for B lymphocytes
to differentiate into antibody-secreting cells. AID and Blimp-1
are elevated in SLE. Reducing AID and Blimp-1 expression in a
mouse model of lupus decreases autoimmunity and improves
health. The hormone estrogen and epigenetic factors called mi-
croRNAs also play roles in AID and Blimp-1 expression.
With the Alliance for Lupus Research grant, his team will sys-
tematically test the ability of different epigenetic modulators to
blunt the lupus autoantibody response and the disease. This grant
complements and expands the scope of two additional and larger
National Institutes of Health research grants that Dr. Casali holds
to address the basic molecular and cellular mechanisms of the an-
tibody response in health and disease. His laboratory is part of
an integrated immunology research operation that also includes
two new junior faculty members who moved with Dr. Casali from
California to San Antonio: Hong Zan, Ph.D., associate professor,
and Zhenming Xu, Ph.D., an assistant professor, both in the De-
partment of Microbiology and Immunology, who focus on the
genetics of the autoimmune response.
We are grateful and excited to have Dr. Casali here continuing
his important work in autoimmune research. I have no doubt it
will have significant implications beyond any single disease. As
well, his partnership with other faculty and leadership for students
and other researchers has already resulted in the creation of a for-
midable team that is addressing the damage done to bodies from
an unregulated immune system.
Learn more about the Department of Microbiology and Im-
munology at http://uthscsa.edu/micro-immunology/index.asp.
Francisco González-Scarano, MD, is dean of
the School of Medicine, vice president for medical
affairs, professor of neurology, and the John P.
Howe III, MD, Distinguished Chair in Health
Policy at the University of Texas Health Science
Center at San Antonio. His email address is
scarano@uthscsa.edu.
visit us at www.bcms.org 33