Looking back on my career in research, I felt that I’ve often lived in the moment and could say I have almost stumbled through science.

Being raised in a predominantly farming community, the idea of doing science as a career was almost unheard of. Throughout my schooling career I had never had much of an interest in biology, with sport garnering much of my attention. Athletics, AFL, football and cricket were my subjects of interest. Growing up with older siblings, we often copy their actions and interests. In addition to our shared love of cooking and baking, I had also picked up my sister’s interest in science! By the end of it all, our proud parents had two children who had completed a PhD. From here, our career paths diverged with her research focus towards microbiology, whereas mine remained in cancer. Today, she spends her time on her true passion, baking, something that I will never be as good at as her.

Looking back on my career in research, I felt that I’ve often lived in the moment and could say I have almost stumbled through science. Even as early as Honours, my field of interest became acute myeloid leukemia (AML), an aggressive and often fatal blood cancer for which I had heard little about prior to starting. Much of my Honours and PhD experience felt like learning on the go as someone who had little biology and lab experience. With this learning came failure which is something of a common theme in research and is not easy to deal with even to this day. At the end of my PhD looking back, it was hard to believe how far I had come. Fortunately, my efforts during my time eventuated in my first publication as a first author (1) with my second one being published later that same week from my current lab (2). I often joke this will be the pinnacle of my research career.

 After completing my PhD in 2019 and coming to Peter Mac for a Post-Doc, this trend of stumbling my way through science continued with my current research focusing on heme metabolism. I remember the day when I went to pitch the idea of working on heme metabolism to my boss, A/Prof Lev Kats. “Heme?!?, isn’t that just important for red blood cells?”. Luckily, the Victorian Cancer Agency thought that studying heme metabolism in AML was important enough to award me an Early Career Research Fellowship in 2022.

Cancer metabolism is a growing area of research interest for drug development to treat AML. To support their metabolic requirements to indefinitely grow, cancer cells leverage specific metabolic pathways allowing those cells to be selectively targeted.  Contrary to what most of us think (including my boss at one point in time), heme is more than just the essential molecule that gives you oxygen to breathe. Heme has several critical biological processes including metabolism, gene expression and detoxification. Furthermore, whole genome knockout studies have shown that leukemia cells are highly reliant on heme to survive.  Despite this critical requirement, why leukemia cells need heme remained unknown. Thus, for once in my science career, I didn’t follow anybody else’s ambitions or interests but instead focused on my own.

In my time examining the heme metabolism, the thing I’ve enjoyed the most is the feeling of pure discovery. In one of my recent experiments examining what genes are important for leukemia cells under different heme conditions, I had found several observations that had no biological explanation. What was most exciting to me from this data was the potential to rewrite the textbook description of how the heme metabolism pathway works. It is times like this that are the reason why I love doing science.

Figure legend: Heme metabolism is altered in AML cells yet is required for several essential biological processes. My research seeks to understand
why heme is required for AML cells to try and develop new treatment strategies.

Dr Alexander Lewis is a postdoctoral researcher in the Kats at the Peter MacCallum Cancer Centre. His work focuses on targeting metabolism in leukemia cells as a therapeutic strategy for the treatment for acute myeloid leukemia and has been published in prestigious cancer journals including Blood and EMBO Molecular Medicine. Alexander receives his support from an Early Career Research Fellowship from the Victorian Cancer Agency.

Email: [email protected]

  1. Lewis AC et al. (2022) “Ceramide- induced integrated stress response overcomes Bcl-2 inhibitor resistance in acute myeloid leukemia” Blood. 139 (26): 3737–3751.
  2. So J*, Lewis AC* et al. (2022) “Inhibition of pyrimidine biosynthesis targets protein translation in AML” EMBO Molecular Medicine

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