Projects per year
Organization 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.
Fields of Science
- 118 Biological sciences
- keyrod here
- 318 Medical biotechnology
- 311 Basic medicine
International and National Collaboration
Profiles
-
Tomi Mäkelä
- Helsinki Institute of Life Science HiLIFE - Research Director
- Department of Biochemistry and Developmental Biology - Professor
- Mäkelä Lab
- 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
-
Inactivation of AMPK Leads to Attenuation of Antigen Presentation and Immune Evasion in Lung Adenocarcinoma
Gao, Y., Päivinen, P., Tripathi, S., Domenech-Moreno, E., Wong, I. P. L., Vaahtomeri, K., Nagaraj, A. S., Talwelkar, S. S., Foretz, M., Verschuren, E. W., Viollet, B., Yan, Y. & Mäkelä, T. P., 1 Jan 2022, In: Clinical Cancer Research. 28, 1, p. 227-237 11 p.Research output: Contribution to journal › Article › Scientific › peer-review
-
Ciliary Hedgehog signaling patterns the digestive system to generate mechanical forces driving elongation
Yang, Y., Paivinen, P., Xie, C., Krup, A. L., Mäkelä, T. P., Mostov, K. E. & Reiter, J. F., 10 Dec 2021, In: Nature Communications. 12, 1, 14 p., 7186.Research output: Contribution to journal › Article › Scientific › peer-review
Open AccessFile -
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
Open AccessFile -
Genetic architecture of human plasma lipidome and its link to cardiovascular disease
FinnGen Project, 24 Sep 2019, In: Nature Communications. 10, 1, 14 p., 4329.Research output: Contribution to journal › Article › Scientific › peer-review
Open AccessFile -
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 AccessFile
Activities
-
Biocenter Finland (External organisation)
Tomi Mäkelä (Board member)
1 Jan 2010 → …Activity: Membership types › Membership or other role in public Finnish or international organization
-
The Cold Spring Harbor Laboratory ‘Epigenetics, Chromatin & Transcription’ meeting
Ying Yang (Poster Presentation)
May 2010Activity: Participating in or organising an event types › Organisation and participation in conferences, workshops, courses, seminars
-
ENFIN (External organisation)
Tomi Mäkelä (Chair)
5 Oct 2010 → 6 Oct 2010Activity: Membership types › Membership or other role in national/international committee, council, board
-
European Research Council, ERC (External organisation)
Tomi Mäkelä (Chair)
Oct 2010 → 31 Dec 2013Activity: Membership types › Assessment of candidates for academic posts
-
Studia Medicina
Tomi Mäkelä (Attendee)
27 Jan 2010Activity: Participating in or organising an event types › Public Talks
Prizes
-
-
Helsingin Yliopiston Biotieteellisen Tiedekunnan Pro Gradu palkinto 2007
Kuuluvainen, Emilia (Recipient), 2007
Prize: Prizes and awards
-
Membeship of the Finnish Academy of Science and Letters
Mäkelä, Tomi (Recipient), 2002
Prize: Prizes and awards
-
The1st prize for the poster, GSBM 2008 annual graduate student meeting
Yang, Y. (Recipient), 2008
Prize: Prizes and awards
Press / Media
-
Connecting energy metabolism to intestinal stem cell fate
15/01/2020
1 item of Media coverage
Press/Media: Press / Media
-
Director General Lea Kauppi selected as one of the top experts for the Horizon Europe
31/07/2019
1 item of Media coverage
Press/Media: Press / Media
-
iCAN: Finland's precision oncology toolbox
Tomi Mäkelä & Miikka Joojakim Korja
18/04/2019
1 item of Media coverage
Press/Media: Press / Media
-
Digital health to support precision cancer medicine in iCAN – a new Academy of Finland flagship
08/01/2019
1 item of Media coverage
Press/Media: Press / Media
-
How this Finnish university is producing future medical pioneers
Tomi Mäkelä, Tiina Immonen & Esko Kankuri
11/09/2018
1 item of Media coverage
Press/Media: Press / Media