Gerta Hoxhaj Lab

Research Focus

Altered metabolism is a hallmark of many diseases, including cancer. Our lab is interested in understanding the molecular fundamentals of how cells rewire their metabolism to fuel the growth and survival of cancer cells. We harness the power of classical biochemistry, metabolomics, cell biology, and mouse models to decode altered metabolism in disease.

Research in our lab is guided by three fundamental questions:

    1. How do cells integrate oncogenic signals to finely regulate their metabolic activities?
    2. How is metabolism linked to tissue function?
    3. How do cells sense metabolite abundance to maintain cellular homeostasis and function?

We believe that advancing our fundamental knowledge of metabolic regulation is the key to unlocking innovative strategies for treating various diseases.

Gerta Hoxhaj received her bachelor’s degree from Bogazici University, Istanbul, Turkey, with a double major in molecular biology and genetics and chemistry….
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Research Projects

Select Publications

Tran, D.H.,* Kim, D.,* Kesavan, R.,* Brown, H., Dey, T., Soflaee, M.H., Vu, H.S., Tasdogan, A., Guo, J., Bezwada, D., Al Saad, H., Cai, F., Solmonson, A., Rion, H., Chabatya, R., Merchant, S., Manales, N.J., Tcheuyap, V.T., Mulkey, M., Mathews, T.P., Brugarolas, J., Morrison, S.J., Zhu, H., DeBerardinis, R.J. and G. Hoxhaj. (2024). De novo and salvage purine synthesis pathways across tissues and tumors. Cell, Epub ahead of print. (PubMed)

Mary, C.,* Soflaee, M.H.,* Kesavan, R., Gelin, M., Brown, H., Zacharias, L.G., Mathews, T.P., Lemoff, A., Leonne, C., Labesse, G.,# G. Hoxhaj.# (2022). Crystal structure of human NADK2 reveals a dimeric organization and active site occlusion by lysine acetylation. Molecular Cell 82, 3299-3311. (PubMed)

Soflaee, M.H.,* Kesavan, R.,* Sahu, U.,* Tasdogan, A., Villa, E., Djabari, Z., Cai, F., Tran, D.H., Vu, H.S., Ali, E.S., Rion, H., O’Hara, B.P., Kelekar, S., Hallett, J.H., Martin, M., Mathews, T.P., Gao, P., Asara, J.M., Manning, B.D.#, Ben-Sahra, I.,# and G. Hoxhaj.# (2022). Purine nucleotide depletion prompts cell migration by stimulating the serine synthesis pathway. Nature Communications 13, 2698. (PubMed)

Tran, D.H.,* Kesavan, R.,* Rion, H., Soflaee, M.H., Solmonson, A., Bezwada, D., Vu, H.S., Cai, F., Phillips, J.A.3rd, DeBerardinis, R.J., and G. Hoxhaj. (2021). Mitochondrial NADP+ is essential for proline biosynthesis during cell growth. Nature Metabolism 3, 571-585. (PubMed)

Hoxhaj, G.,# and B.D. Manning.# (2020). The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism. Nature Reviews Cancer 116, 2539-2544. (PubMed)

Hoxhaj, G., Ben-Sahra, I., Lockwood, S.E., Timson, R.C., Byles, V., Henning, G.T., Gao, P., Selfors, L.M., Asara, J.M., and B.D. Manning. (2019). Direct stimulation of NADP+ synthesis through Akt-mediated phosphorylation of NAD kinase. Science 363, 1088-1092. (PubMed)

Hoxhaj, G., Hallett, J.H., Timson, R., Ilagan, E., Asara, J.M., Ben-Sahra, I., and B.D. Manning. (2017). The mTORC1 signaling network senses changes in cellular purine nucleotide levels. Cell Reports 21, 1331-1346. (PubMed)

Ben-Sahra, I.,* Hoxhaj, G.,* Ricoult, S.J., Asara, J.M., and B.D. Manning. (2016). mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle. Science 351, 728-33. (PubMed)

Hoxhaj, G.,# Caddye, E., Najafov, A., Houde, V.P., Johnson, C., Dissanayake, K., Toth, R., Campbell, D.G., Prescott, A.R., and C. MacKintosh.# (2016). The E3 ubiquitin ligase ZNRF2 is a substrate of mTORC1 and regulates its activation by amino acids. eLife pii: e12278. (PubMed)

Hoxhaj, G.,# Najafov, A., Toth, R., Campbell, D.G., Prescott, A.R., and C. MacKintosh.# (2012). ZNRF2 is released from membranes by growth factors and, together with ZNRF1, regulates the Na+/K+ATPase. Journal of Cell Science 125, 4662-75. (PubMed)

*Contributed equally

#Co-corresponding author

Lab Members

Mona Hoseini Soflaee, Ph.D.

Scientist, AstraZeneca
Postdoctoral Fellow (2020-2023)

Harrison Brown, B.S.

Graduate Student, UT Southwestern
Research Assistant (2021-2023)

Halie Rion, B.S.

Clinical Specialist, Strata Skin Sciences
Research Assistant (2020-2021)

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