Spring Martlet 2017

INVESTIGATING
AGING PROCESSES
ASSOCIATED WITH
OSTEOARTHRITIS
Pradeep Sacitharan (2012, Medicine
– DPhil Musculoskeletal Sciences) a
final year DPhil graduate focusing on
ageing biology, is currently based in the
Kennedy Institute of Rheumatology
and the Arthritis Research UK Centre
for Osteoarthritis Pathogenesis at the
Nuffield Department of Orthopaedics,
Rheumatology and Musculoskeletal
Sciences, at the University of Oxford.
The Martlet caught up with him in the
lab to discuss his project to develop a
new drug that might have a significant
impact on treating Osteoarthritis in
the future.
After finishing my Master’s degree I wanted
to focus on hard problems in the field
of medicine that will be a huge societal
burden in the future. The average lifespan
of individuals across the globe is increasing
which will result in a dramatic increase in agerelated
diseases such as Parkinson’s disease,
Alzheimer’s disease and osteoarthritis. The
increased incidence of these diseases will
subsequently increase healthcare costs.
Hence, I set out to address one of these key
aged-related diseases during my DPhil.
Osteoarthritis is the most common form of
arthritis worldwide and patients suffer from
severe pain, distress and restricted movement.
Osteoarthritis occurs when cartilage tissue
located on the top of articular joints which
provide protection and lubrication for
movement is degraded away over time.
There are no effective treatment options for
osteoarthritis. Age is the primary risk factor
for the disease, however, little is known on
why the prevalence of osteoarthritis increases
with age. My DPhil research is centred on
investigating ageing processes in cartilage
associated with osteoarthritis.
For the last twenty years, an enzyme called
SIRT1 has been extensively shown to
control various age-related cellular pathways.
My project aimed to explore the role of
SIRT1 in osteoarthritis and to investigate
its therapeutic potential to treat the
disease. At first I showed SIRT1 declines in
human cartilage over time. Thereafter, using
new ways to manipulate genes in mice I
discovered how SIRT1 controls the ageing
process in cartilage. I unravelled that SIRT1
controls autophagy, a process that recycles
unwanted and defective proteins in cartilage.
After observing the link between SIRT1 and
autophagy I developed a drug to activate
this critical link and showed a reduction in
osteoarthritis in mice. This treatment option
can now be taken to early clinical trials to
see if it is effective in managing osteoarthritis
in humans. I am honoured that my DPhil
discoveries have resulted in several awards:
• American Society for Bone and Mineral
Research New Investigator Award
• European Calcified Tissue Society New
Investigator Award
• British Bone Research Society New
Investigator Award
• British Bone Research Society best oral
communication award
• Nature Reviews Rheumatology
international best talk award
• University of Oxford Medical Sciences
Divisional 3 minute thesis champion
I have thoroughly enjoyed my DPhil over the
last four years. Univ has been an amazing
place to conduct my doctoral studies. I
chose Univ due to its historical age, notable
alumni, and the opportunity to meet fellow
students from a breadth of specialities
and the upside of great food especially at
brunch on the weekends. Moreover, my
College tutor, colleagues and the Dean
of Graduate Studies have been very
supportive throughout my DPhil journey. I
thank everyone at the College for their kind
support over the years.
I believe my experience at the University
of Oxford and Univ will put me in a strong
position to achieve my short-term goal of
starting my own research lab concentrating
on targeting pathways to treat chronic
inflammatory diseases associated with ageing.
My long term dream is to be a director of
an institute concentrating on treating and
curing these diseases by applying cutting
edge technology, recruiting the brightest
researchers and providing educational
opportunities to the best young talent from
all around the world.
18 THE MARTLET | SPRING 2017