A Flexible Mind to Solve Stiff Joints: Dr. Amanda Ali’s Journey in Osteoarthritis Research

Article by Archita Srinath, Shahrzad Firouzian & Natalie Osborne

Graphic design by Ava Schroedl

Establishing your own research lab in academia sometimes feels like a near-impossible feat achieved only by those with a singular focus and the best laid plans. But dedication, curiosity, flexibility, and the courage to do things “differently” can be just as important to success. These are the qualities exemplified by IMS alumni Dr. Amanda Ali, who shared her unique journey from grad student to Assistant Scientist at Henry Ford Health System in Detroit, Michigan.

Dr. S Amanda Ali, Assistant Scientist, Henry Ford

Photo credit: Tim Fraser (UHN)

Starting university, Dr. Ali did not know what she wanted as a future career, so she kept her options open. By the time she decided to take on a research project in her 4th year, most lab positions had already been filled up. So, she had a decision to make; either forgo research altogether or self-advocate until a position was created for her.  She managed to secure a position in a plant biology lab, seizing the opportunity to build her research skills and even publish a paper. Even though she describes her time at this lab as “a challenging change of pace”, she still enjoyed what she learned and decided to continue her research career through graduate studies with the IMS.  

“When the time came to decide on a supervisor, I had two research areas I was interested in; osteoarthritis (OA) and diabetes, because I had two grandmas suffering with each disease.  I thought this would give me personal motivation to spend the next however many years toiling away learning about these conditions,” explains Dr. Ali.

She ultimately chose to work with Dr. Benjamin Alman, an orthopeadic surgeon with the Hospital for Sick Children with access to clinical samples. Dr. Alman’s lab was large and had a great breadth of knowledge on various musculoskeletal disorders, which Dr. Ali felt would inform her own project. And so began her (now illustrious) research career in OA, a disease that involves the wearing down of the protective cartilage on the ends of bones, and which currently has no cure.

Dr. Ali quickly transferred from an MSc to a PhD, with an ambitious project on the hedgehog signalling pathway, which is important for the development of the musculoskeletal system. This pathway, which normally should be inactive in adults, becomes active during OA, and is thought to drive some of the pathologies seen in patients. Dr. Ali’s aim was to determine how this occurred, and she made a critical discovery – that hedgehog signalling was regulating cholesterol stores within individual cells in the cartilage, and exacerbating OA. While cholesterol’s role in OA had previously been explored, Dr. Ali was the first to demonstrate intracellular [disbalances] in cholesterol homeostasis.

“I was very fortunate to have built an amazing network of people, but this only started towards the end of my PhD. In the beginning I was sort of a fish out of water – I had very little research experience in molecular biology, so it took me a long time to get my bearings and learn some of the basic techniques that my peers already had mastered,” explains Dr. Ali. “At a critical point I met my (then and now) best friend Natalie Vanier – the founding editor of IMS Magazine. She was one of those really instrumental people in my life who helped me become more involved.”

Dr. Ali’s involvement with the magazine allowed her to develop and flex her “writing muscles” and learn that writing was an outlet for her.  She became an exceptionally skilled science communicator whose articles remain some of the most read IMS pieces to this day. Dr. Ali credits her IMS Magazine experience with shaping her career and improving her experience of science; “Not only was I engaged in science, I also saw myself as someone who was commenting on science. I had the opportunity to formulate and express my opinion on relevant hot topics and ongoing issues,” she explains. Dr. Ali still applies these writing skills daily, from popular press articles to scientific manuscripts and grants, and finds writing in a personal journal to be a therapeutic way to express herself.

But at the end of her PhD, Dr. Ali came to a crossroads; “I was convinced I would never do a postdoc. I was really burned out, I didn’t want to continue in the lab, I didn’t want to see another mouse, I didn’t want to run another PCR. So I started to explore every possible avenue for what I could use my PhD for and how I could build my career beyond the IMS.” A career in science writing was a reassuring backup plan, but she systematically ruled out the common alternatives, industry, pharma, and government. “I realized that I really did love research, I loved the pursuit of knowledge; I was just tired.”

It was then Dr. Ali decided to make a strategic move in her career – instead of pursuing a postdoc in the molecular biology of OA, she would study the same disease but from a vastly different perspective. She won a fellowship for a postdoc position in applied research at Western University that used qualitative methods to study how OA is managed in community settings. While information on helpful OA management strategies is available, patients are not always aware that these resources exist. Under the supervision of Drs. Joy MacDermid and Marita Kloseck, Dr. Ali explored programs to allow seniors in the community to take OA pain management into their own hands.

“My basic science colleagues couldn’t understand why I wanted to switch to a “softer” type of research, as they viewed it. Similarly, the applied researchers viewed me at first as someone with no experience, no appreciation, and no understanding of their methods. So initially I was criticized on both sides,” explains Dr. Ali. “At the same time, I was motivated to bridge those two research silos. I realized that learning both “languages” would help me be a better communicator, do more translational research, and overcome some of the systemic barriers that exist when trying to translate basic research findings to clinical practice.”

Now equipped with a PhD in basic science and a postdoc in applied research, Dr. Ali felt she was missing the middle piece – an understanding of the clinical research that bridges the lab and the community. For her second postdoc, she joined the Arthritis Program at the University Health Network (UHN) under the supervisions of Drs. Mohit Kapoor and Rajiv Gandhi. Here, Dr. Ali delved into translation research investigating biomarkers for early OA detection, which would make interventions at the community level more effective. She was able to optimize a technique used for next generation sequencing of patient blood samples from a large biobank. Interestingly, Dr. Ali had first encountered gene sequencing during her PhD and found it puzzling and extremely sophisticated. As a postdoc, she mastered this technology to study patients’ unique phenotypes at an individual level, and then explored how these results could be categorized at a systematic level to understand what was occurring at different stages of the disease.

In this manner Dr. Ali created a unique niche for herself. She was recruited as an Assistant Scientist to the Bone and Joint Centre at Henry Ford Hospital for her expertise in genomic technologies as well as her translational background in OA. Her research goals now include a move towards precision medicine in OA: using genetics to individualize patient care. She hopes to dispel common misconceptions about OA; that it is an “inevitable” part of ageing, or that there’s “nothing” you can do about it. She says that although there is no cure, there are good clinical guidelines for OA prevention and management.

“It’s a bit counter-intuitive, but exercise is the best thing you can do to delay progression of the disease; both targeted exercises to strengthen specific muscles, and general aerobic activity,” explains Dr. Ali. “Tailoring exercise prescriptions to patients is one of the many areas that needs to be developed, so that when my work is applied to diagnose the disease at earlier stages, we know how to make sure they’re taking the best care to delay its progression.”

The COVID-19 pandemic started three months into running her own lab, and Dr. Ali found it difficult to hire new research staff, begin wet lab work and participate in networking events with her colleagues. However, she is overwhelmed with gratitude for being able to do a job that she loves. When asked what advice she could give to students considering the academic route, Dr. Ali says that flexibility in terms of research program and geography are key to finding opportunities.

“I think the early establishment of a unique set of skills that distinguishes you from your peers, either within or beyond academia (i.e., learning diverse research methods or science communication) is of vital importance,” Dr. Ali advises.

So, what can we learn from Dr. Ali’s career path? We can worry a little less about defining and diligently sticking to a plan for our careers knowing that the journey to success may take us to places that we could never have imagined!