Dr Gerta Hoxhaj – a PhD student in Carol MacKintosh’s lab in the MRC PPU from 2008-2013 – has won the prestigious 2024 Vilcek Prize for Creative Promise in Biomedical Science.
“I am very honored and humbled to receive the Vilcek Prize for Creative Promise in Biomedical Science. This award is very special for me, as it not only recognizes my scientific contributions but also highlights my unique journey as an immigrant scientist, the challenges, and perseverance in pursuing my scientific dream. This award also motivates me to continue pushing the boundaries of science and to mentor and support the next generation of scientists.”
Here, Gerta shares her journey as an immigrant scientist, discussing how her PhD at the MRC PPU was “truly formative” for her scientific career, and where her inspiration and motivation comes from.
Life as an immigrant scientist
Gerta was born in Fier, Albania and was naturally drawn towards maths and science from a young age. She left home when she was just fourteen years old to attend High School in Albania’s capital city, Tirana, where her passion for biology grew deeper.
At eighteen, Gerta had to make a tough decision between accepting a scholarship she’d been offered to study Medicine in Italy or a scholarship to study Molecular Biology in Turkey. As the granddaughter of a doctor, Gerta had always imagined she’d become a doctor and had even taken the Italian language exam to prepare to study in Italy, but her parents supported her to follow her love for science and molecular biology.
“Istanbul was a beautiful place with nice people. The courses were taught in English at Bosphorus University, and there was a community of other Albanian students, making the transition at a young age a bit easier.
It is challenging being an immigrant scientist, as you have to leave your family and friends behind, adapt to new environments and cultures, be competitive at every stage of the career, and deal with the added stress of visas. You have to create your own support system – and heavily rely on yourself.”
During her time at Bosphorus University in Istanbul, Gerta met a Master Student who spoke highly of their lab experience at the University of Dundee. Feeling inspired, Gerta secured a summer internship in Angus Lamond's lab in Dundee during the second year of her Bachelor’s degree. She loved being in the lab doing experiments and the “exceptionally welcoming and friendly” community, prompting her to apply to the MRC PPU for her PhD studies.
“Formative” years at the MRC PPU
“My time at the MRC PPU was truly formative for my scientific career.
People in the MRC PPU really care deeply about doing rigorous science, and the MRC PPU has an amazing reputation worldwide.
Attending and presenting our work at pharma meetings and scientific retreats was critical for my scientific training, as these events exposed me to a wide range of science and scientific approaches. Learning from talented students and postdocs and receiving constructive feedback from faculty were invaluable experiences.
My PhD mentor, Carol MacKintosh, is a wonderful mentor, and one of the kindest people I have met. She gave me the freedom to explore different directions, and I learned a lot. Carol’s lab was very friendly, and many of my closest friends today are from Carol's lab or other MRC-PPU alumni.
The most fond memories of my career are in Dundee. There’s a uniquely friendly and collaborative environment in the MRC PPU - I really loved the open plan lab layout and shared tissue culture facilities, as it was a place where you got to know all other PhD students and postdocs at the Unit.
There is still a strong sense of camaraderie among MRC PPU graduates, a testament to the strong foundation and lasting connections built during our time there.
The strong training I received at MRC PPU in biochemistry, kinase signaling, and protein research has laid a strong foundation for my career and the research approach in my own lab.”
Motivation and inspiration
Gerta, who calls herself a “science nomad”, has moved from one country to another for each stage of her career - starting in Albania, then moving to Istanbul, Dundee, Boston, and finally, Dallas. After undertaking her Postdoctoral research at Harvard University, she started her lab at UT Southwestern Medical Center, in Dallas, Texas, as “like Dundee, it has outstanding science and colleagues and a supportive environment.”
Her passion for science is infectious. She is motivated by an innate curiosity and a drive to find answers to big questions – an outlook she also encourages amongst the PhD students and Post-doctoral researchers in her lab.
Gerta’s research seeks to understand how cancer cells adjust their metabolism to help them grow and survive. By understanding these changes, she aims to find new ways to target and treat cancer.
“One of my main research interests is to decipher the mechanisms that allow cancer cells to produce the cofactor NADPH - a major reducing currency required to protect cells from oxidative stress and promote anabolic processes that sustain proliferation. NADPH exists in separate compartments, in the cytosol and mitochondria. However, we have a limited understanding of the biological functions and regulation of NADPH pools across compartments. Mitochondrial NADPH has been thought to be primarily used to detoxify reactive oxygen species (ROS). In my lab, we made a surprising finding that depleting mitochondrial NADPH did not increase sensitivity to ROS, but instead made the cells incapable of synthesizing proline, thereby uncovering a novel metabolic liability that can be exploited to target cancer.
Cancer is a devastating disease. I hope that our research on cancer metabolism not only significantly enhances our understanding of this complex disease but also leads to a major breakthrough that makes a difference in people's lives.”
When taking time out from balancing the various responsibilities of a Principal Investigator, Gerta also finds inspiration in nature, “I find nature beautiful and miraculous, giving me a sense of peace and calmness.”
Final thoughts
“I feel incredibly fortunate to have been trained at the MRC PPU, an incredibly stimulating environment. MRC PPU is all about rigorous science and strong work ethic. At the same time, it is a wonderful community, and it is easy to connect with many people during Friday socials, events and parties hosted by students/postdocs, and, of course the famous Ceilidh dances.”
Gerta’s advice to those looking to start a PhD in the MRC PPU is “Perseverance is key, and remember that hard work always pays off. I’ve always felt privileged to have trained at the cradle of kinase signaling, so take advantage of the outstanding training, resources, environment at MRC PPU, and always stay curious.”
MRC PPU Director, Dario Alessi, commented "The Unit is very proud of Gerta’s achievements and wish her every success for the future."
Top publications
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Hoxhaj, G, I Ben-Sahra, S Evarts, RC Timson, V Byles, GT Henning, P Gao, LM Selfors, JM Asara, and BD Manning. 2019. Direct stimulation of NADP+ synthesis through Akt-mediated phosphorylation of NAD Kinase. Science 363:1088-1092. PMID 30846598.
The metabolite cofactor, NADPH, provides a reservoir of electrons for anabolic reactions, and defense against oxidative stress. The synthesis of NADPH is maintained by NAD kinases (NADK), metabolite kinases that phosphorylate NAD+ molecules to make NADP+, a limiting substrate for the generation of NADPH. During my postdoc, I found that the PI3K-Akt pathway stimulated the activity of NADK, thereby boosting NADP(H) production to support cancer cell growth. We also revealed an autoinhibitory function for the N-terminal regulatory domain of NADK, likely indicating that other signaling events could impinge on this domain to adjust NADP(H) pool available for cellular reducing power.
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Tran DH, Kesavan R, Rion H, Hoseini Soflaee M, Solmonson A, Bezwada D, Vu HS., Cai F, Solmonson A, Phillips JA III, DeBerardinis RJ, Hoxhaj G. Mitochondrial NADP+ is essential for proline biosynthesis during cell growth. Nat Metab, 2021, PMID: 33833463,
Cells maintain NADPH pools in separate compartments, including the cytosol and mitochondria. NADPH synthesis is sustained by cytosolic NADK and mitochondrial NADK2, which provide NADPH-reducing power in each location.
While cytosolic NADPH is thought to be used chiefly for biosynthetic processes, the long-standing paradigm suggests that mitochondrial NADPH is primarily used to detoxify ROS. Work from my laboratory demonstrated that NADK2’s major role in proliferating cells is to enable the synthesis of proline to support protein synthesis. This work increases our understanding of NADPH metabolism by revealing that location dictates the specific metabolic functions of this cofactor. It also opens up the possibility of targeting cancers with high proline requirements by inhibiting NADK2.
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Mary C, Soflaee MH, Kesavan R, Gelin M, Brown H, Zacharias G, Mathews TP, Lemoff A, Lionne C, Labesse G, Hoxhaj G. Crystal structure of human NADK2 reveals a dimeric organization and active site occlusion by lysine acetylation. Mol Cell 2022, PMID: 35868311.
Here, we reported the crystal structure of human NADK2, revealing important molecular insight into the structure and regulation of a vital enzyme in mitochondrial NADPH and proline metabolism.
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Interview date: April 2024
Written by: Sarah Patrick, Communications & Public Engagement & Involvement Consultant