Projects per year
Organization profile
Organisation Profile
Our longstanding interest is to characterize signaling pathways regulating mammalian cell growth and how these impinge on transcriptional responses in human disease
Two critical mediators of transcriptional responses involved in cancer and metabolism aretranscriptional kinases Cdk7 and Cdk8 mediating signals to RNA polymerase II. We are investigating the molecular mechanisms and in vivo functions of Cdk7 and Cdlk8 combining mouse molecular genetics with Drosophila knockdown strategies and cell-based screening approaches. Recent discoveries include identifying that Cdk7 acts as a roadblock to adipogenesis and that this presumed ubiquitous basal transcription factor is not expressed in fat tissues. Our goal is to understand the basis for the specificity of transcriptional regulation by metazoan Cdk7 and Cdk8 and their contribution to growth control and differentiation.
One of the rare kinases acting normally to restrict tumor growth is the LKB1ser- ine/threonine kinase critical for activation of at least 14 related kinases involved in metabolism and polarity regulation. We are interested in how LKB1 mediates its tumor suppressing function, and recently identified that LKB1 signaling in mesen- chymal cells is required for suppression of epithelial hyperproliferation in a mouse polyposis model and likely also in the human Peutz-Jeghers syndrome. We are cur- rently extending investigations of tumor suppression mechanisms of the LKB1 tu- mor suppressor kinase from hereditary polyposis to sporadic cancer (lung, uterine cervix). For this a combination of tissue- and cell type specific targeting approaches in vivo (conditional mouse models) and in vitro (2D and 3D RNAi & conditional dele- tions) of LKB1 and LKB1 substrate mutations will be used with a specific interest in the Nuak2 and AMPK kinases and cytoskeletal regulation.
International and National Collaboration
Publications and projects within past five years.
Profiles
Tomi Mäkelä
- Department of Biochemistry and Developmental Biology - Professor
- Mäkelä Lab
- Helsinki Institute of Life Science HiLIFE - Research Director
- Doctoral Programme in Integrative Life Science - Supervisor for doctoral programme
Person: UH, U4 Research and teaching staff
Projects
- 1 Active
Kinase signaling linking metabolism and growth control
Conversion, U. P. M.
01/01/1996 → …
Project: Research project
Publications
LKB1 Represses ATOH1 via PDK4 and Energy Metabolism and Regulates Intestinal Stem Cell Fate
Gao, Y., Yan, Y., Tripathi, S., Pentinmikko, N., Amaral, A., Päivinen, P., Domenech-Moreno, E., Andersson, S., Wong, I. P. L., Clevers, H., Katajisto, P. & Mäkelä, T. P., Apr 2020, In : Gastroenterology. 158, 5, p. 1389-+ 23 p.Research output: Contribution to journal › Article › Scientific › peer-review
Depletion of Mediator Kinase Module Subunits Represses Superenhancer-Associated Genes in Colon Cancer Cells
Kuuluvainen, E., Domenech-Moreno, E., Niemela, E. H. & Makela, T. P., Jun 2018, In : Molecular and Cellular Biology. 38, 12, 15 p., UNSP e00573-17.Research output: Contribution to journal › Article › Scientific › peer-review
Open Access
File
Increased alpha-actinin-1 destabilizes E-cadherin-based adhesions and associates with poor prognosis in basal-like breast cancer
Kovac, B., Makela, T. P. & Vallenius, T., 9 May 2018, In : PLoS One. 13, 5, 20 p., 0196986.Research output: Contribution to journal › Article › Scientific › peer-review
Open Access
File
Stromal Lkb1 deficiency leads to gastrointestinal tumorigenesis involving the IL-11-JAK/STAT3 pathway
Ollila, S., Domenech-Moreno, E., Laajanen, K., Wong, I. P. L., Tripathi, S., Pentinmikko, N., Gao, Y., Yan, Y., Niemelä, E. H., Wang, T. C., Viollet, B., Leone, G., Katajisto, P., Vaahtomeri, K. & Mäkelä, T. P., 2 Jan 2018, In : Journal of Clinical Investigation. 128, 1, p. 402-414 13 p.Research output: Contribution to journal › Article › Scientific › peer-review
Open Access
AMPK negatively regulates tensin-dependent integrin activity
Georgiadou, M., Lilja, J., Jacquemet, G., Guzman, C., Rafaeva, M., Alibert, C., Yan, Y., Sahgal, P., Lerche, M., Manneville, J-B., Makela, T. P. & Ivaska, J., Apr 2017, In : Journal of Cell Biology. 216, 4, p. 1107-1121 15 p.Research output: Contribution to journal › Article › Scientific › peer-review
Open Access
File
Activities
Scientific Reports (Journal)
Tomi Mäkelä (Reviewer)6 Dec 2010 → …
Activity: Publication peer-review and editorial work types › Editor of research journal
Univ Helsinki, Faculty of Medicine (External organisation)
Tomi Mäkelä (Chair)3 Jun 2010
Activity: Membership types › Membership or other role in national/international committee, council, board
The Cold Spring Harbor Laboratory ‘Epigenetics, Chromatin & Transcription’ meeting
Ying Yang (Poster Presentation)May 2010
Activity: Participating in or organising an event types › Organisation and participation in conferences, workshops, courses, seminars
Studia Medicina
Tomi Mäkelä (Attendee)27 Jan 2010
Activity: Participating in or organising an event types › Public Talks
ENFIN (External organisation)
Tomi Mäkelä (Chair)5 Oct 2010 → 6 Oct 2010
Activity: Membership types › Membership or other role in national/international committee, council, board
Prizes
Helsingin Yliopiston Biotieteellisen Tiedekunnan Pro Gradu palkinto 2007
Emilia Kuuluvainen (Recipient), 2007
Prize: Prizes and awards
Membeship of the Finnish Academy of Science and Letters
Tomi Mäkelä (Recipient), 2002
Prize: Prizes and awards
The1st prize for the poster, GSBM 2008 annual graduate student meeting
Ying Yang (Recipient), 2008
Prize: Prizes and awards
Press / Media
Annual Centre of Excellence seminar: Peer review easier in life sciences
14/12/2010
1 Media contribution
Press/Media: Press / Media
Radiaattori: telomeraasista Nobel / Sisko Loikkanen
21/10/2010
1 Media contribution
Press/Media: Press / Media
Tomi Mäkelä Helsingin biotekniikan instituutin johtoon
16/01/2009
1 Media contribution
Press/Media: Press / Media
Science Days Finland 2007: Opportunities from Cancer Biology
10/01/2007
1 Media contribution
Press/Media: Press / Media