Tak Mak

The main interest in my laboratory is to understand genetic and biochemical pathways of I) lymphocyte activation ii) cell survival and apoptosis. To this end, we utilize multiple technologies to dissect these pathways. In the first case, our interests are mainly in the mechanisms of T cell costimulation.  For the latter situation, we concentrate on the three signaling cascades that lead to cell survival, and other cellular functions, namely, those leading to the activation of the transcription factors NFkB and those affected by the tumour suppressor gene PTEN or PI3,Kinase. We are also interested in how the tumour suppressor gene p53 can exert its effects on cell cycle arrest and apoptosis. To advance our knowledge, we utilize a variety of technologies, including microarray gene profiling, genetic modifying screens and expression cloning to identify new genes and document relationships between known genes in these pathways. Biochemical studies are also employed to establish these genetic links. Finally, we generate mutant mouse models study the physiological roles of these genes.

A recent example of our findings in the NFkB pathways include the identification of the role of BCL10 as a gene involved in antigen receptor signaling for the activation of these transcription factors. For the PTEN pathways, we demonstrated that DJ-1 may impact on the function of this tumour suppressor gene by regulation the stability of the RNA of this phosphatase. We hope that our findings will enrich the knowledge of these physiologically important pathways and allow the identification of mechanistically based drug targets for the treatment of autoimmune disorders and malignancies.

Recent Publications

1. Yanagi, Y., Yoshikai, Y., Leggett, K., Clark, S.P., Aleksander, I. & Mak, T.W. Nature 308, 145-149 (1984).
2. Lewis, W.H., Michalopoulos, E.E., Williams, D.L., Minden, M.D. & Mak, T.W. Nature 317, 544-546 (1985).
3. Pfeffer, K., Matsuyama, T., Kündig, T.M., Wakeham, A., Kishihara, K., Shahinian, A., Wiegmann, K., Ohashi, P.S., Krönke, M. & Mak, T.W. Cell73, 457-467 (1993).
4. Shahinian, A., Pfeffer, K., Lee, K., Kundig, T., Kishihara, K., Wakeham, A., Kawai, K., Ohashi, P., Thompson, C. & Mak, T.W. Science 261, 609-612 (1993).
5. Matsuyama, T., Kimura, T., Kitagawa, M., Pfeffer, K., Kawakami, T., Watanabe, N., Kundig, T.M., Amakawa, R., Kishihara, K., Wakeham, A., Potter, J., Furlonger, C.L., Narendran, A., Suzuki, H., Ohashi, P.S., Paige, C.J., Taniguchi, T. & Mak, T.W. Cell 75, 1-20 (1993).

Appointments