Metabolic disorders and liver disease
Department of Clinical Sciences Malmö
PI: Philipp Kaldis
We are a research group that strives for excellency and are interested in how cell cycle regulation integrates with signaling pathways in the context of human disease.
Our main focus in on liver diseases and how they are affecting metabolism as a function of the ability of hepatocytes to divide. This is important since the liver has a surprising capacity to regenerate, which is driven by differentiated hepatocytes re-entering the cell cycle to self-renew. This capacity is thought to be important for the liver to deal with extrinsic and intrinsic insults as well as maintaining liver homeostasis. We have uncovered that metabolism is remodeled when hepatocytes cannot divide as has been observed in liver diseases.
Currently we are pursuing the following aims:
To investigate how cyclin-dependent kinases (CDKs) or other cell cycle regulators control metabolism in the context of liver diseases like NAFLD and NASH.
To study glucose metabolism globally with a focus of comparing several tissues using “omics” approaches. The data from these tissues will be compared to the liver, which is a major hub in regards to glucose metabolism.
To study how glucose and lipid metabolism are cross-regulating themselves in the context of the liver but by interacting with other tissues (adipocytes, etc.).
In addition, we have done considerable amounts of work to determine the functions of CDKs in fertility.
Caldez, M.J.*, Björklund, M., and Kaldis, P.* (2020) Cell cycle regulation in NAFLD : When imbalanced metabolism limits cell division. Hepatology International, in press.
Niska-Blakie, J., Gopinathan, L., Low, K.N., Kien, Y.L., Goh, C.M.F., Caldez, M.J., Pfeiffenberger, E., Jones, O.S., Ong, C.B., Kurochkin, I., Coppola, V., Tessarollo, T., Choi, H., Kanagasundaram, Y., Eisenhaber, F., Maurer-Stroh, S.*, and Kaldis, P.* (2020) Knockout of the non-essential gene SUGCT creates diet-linked, age-related microbiome disbalance with a diabetes-like metabolic syndrome phenotype. Cell. Mol. Life Sci., 76, in press. doi: 10.1007/s00018-019-03359-z.
Caldez, M.J., Van Hul, N., Koh, H.W.L., Teo, X.Q., Fan, J.J., Tan, P.Y., Dewhurst, M.R., Too, P.G., Talib, S.Z.A., Chiang, B.E., Stünkel, W., Yu, H., Lee, P., Fuhrer, T., Choi, H., Björklund, M., and Kaldis, P.* (2018) Metabolic remodeling during liver regeneration. Developmental Cell, 47, 425-438.
Palmer, N., Talib, S.Z.A., Ratnacaram, C.K., Low, D., Bisteau, X., Lee, J.H.S., Pfeiffenberger, E., Wollmann, H., Tan, J.H.L., Wee, S., Sobota, R., Gunaratne, J., Messerschmidt, D., Guccione, E.*, and Kaldis, P.* (2019) CDK2 regulates the NRF1/Ehmt1 axis during meiotic prophase I. J. Cell Biol., 218, 2896-2918.
Palmer, N.*, Talib, S.Z.A., and Kaldis, P.* (2019) Diverse roles for CDK-associated activity during spermatogenesis. FEBS Letters, 593, 2925-2949.
Windpassinger, C., Piard, J., Bonnard, C., Alfadhel, M., Lim, S., Bisteau, X., Blouin, S., Ali, N.A.B., Ng, A.Y.U., Lu, H., Tohari, S., Talib, S.Z.T., Van Hul, N., Caldez, M.J., Van Maldergem, L., Yigit, G., Kayserili, H., Youssef, S.A., Coppola, V., de Bruin, A., Tessarollo, L., Choi, H., Rupp, V., Rötzer, K., Roschger, P., Klaushofer, K., Altmüller, J., Roy, S., Venkatesh, B., Ganger, R., Grill, F., Chehida, F.B., Wollnik, B., Altunoglu, U., Al Kaissi, A., Reversade, B.*, and Kaldis, P.* (2017) CDK10 mutations in humans and mice cause severe growth retardation, spine malformations and developmental delays. Am. J. Hum. Genet., 101, 391-403.
Diril, M.K., Bisteau, X., Kitagawa, M., Caldez, M.J., Wee, S., Gunaratne, J., Lee, S.H., and Kaldis, P.* (2016) Loss of the Greatwall kinase weakens the spindle assembly checkpoint. PLOS Genetics, 12, e1006310.
Interested in working in our lab?
Please contact Philipp Kaldis (philipp [dot] kaldis [at] med [dot] lu [dot] se)