Projekt per år
Organisationsprofil
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.
Vetenskapsgrenar
- 118 Biovetenskaper
- 318 Medicinsk bioteknologi
- 311 Basmedicin
Internationellt och inhemskt samarbete
Personer
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Tomi Mäkelä
- Helsinki Insitute of Life Science HiLIFE - forskningsdirektör
- Avdelningen för biokemi och utvecklingsbiologi - professor
- Tomi Mäkelä / Ansvarig forskare
- Doctoral Programme in Integrative Life Science - Handledare för doktorandprogram
Person: HU, U4 Undervisnings- och forskningspersonal
Projekt
- 1 Aktiv
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Kinase signaling linking metabolism and growth control
Conversion, U. P. M.
01/01/1996 → …
Projekt: Forskningsprojekt
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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, I: Clinical Cancer Research. 28, 1, s. 227-237 11 s.Forskningsoutput: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review
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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, I: Nature Communications. 12, 1, 14 s., 7186.Forskningsoutput: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review
Öppen tillgångFil -
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, I: Gastroenterology. 158, 5, s. 1389-+ 23 s.Forskningsoutput: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review
Öppen tillgångFil -
Genetic architecture of human plasma lipidome and its link to cardiovascular disease
FinnGen Project, 24 sep. 2019, I: Nature Communications. 10, 1, 14 s., 4329.Forskningsoutput: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review
Öppen tillgångFil -
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., juni 2018, I: Molecular and Cellular Biology. 38, 12, 15 s., UNSP e00573-17.Forskningsoutput: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review
Öppen tillgångFil
Aktiviteter
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Biocenter Finland (Extern organisation)
Tomi Mäkelä (Styrelsemedlem)
1 jan. 2010 → …Aktivitet: Medlemskapstyper › Medlemskap eller annan roll i inhemskt/internationellt offentligt organ
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Scientific Reports (Tidskrift)
Tomi Mäkelä (Referentgranskare)
6 dec. 2010 → …Aktivitet: Typer för peer review av output och redaktionsarbete › Redaktör för vetenskaplig tidskrift
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ENFIN (Extern organisation)
Tomi Mäkelä (Ordförande)
5 okt. 2010 → 6 okt. 2010Aktivitet: Medlemskapstyper › Medlemskap eller annan role i inhemsk/internationell kommitté, råd, styrelse
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European Research Council, ERC (Extern organisation)
Tomi Mäkelä (Ordförande)
okt. 2010 → 31 dec. 2013Aktivitet: Medlemskapstyper › Utlåtanden vid tillsättning
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Univ Helsinki, Faculty of Medicine (Extern organisation)
Tomi Mäkelä (Ordförande)
3 juni 2010Aktivitet: Medlemskapstyper › Medlemskap eller annan role i inhemsk/internationell kommitté, råd, styrelse
Priser
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Anders Jahre Young Investigator Award
Mäkelä, Tomi (!!Recipient), 1 jan. 2005
Pris: Pris och hedersbetygelser
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Helsingin Yliopiston Biotieteellisen Tiedekunnan Pro Gradu palkinto 2007
Kuuluvainen, Emilia (!!Recipient), 2007
Pris: Pris och hedersbetygelser
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Membeship of the Finnish Academy of Science and Letters
Mäkelä, Tomi (!!Recipient), 2002
Pris: Pris och hedersbetygelser
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The1st prize for the poster, GSBM 2008 annual graduate student meeting
Yang, Y. (!!Recipient), 2008
Pris: Pris och hedersbetygelser
Tidningsurklipp
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Connecting energy metabolism to intestinal stem cell fate
15/01/2020
1 objekt av Mediabevakning
Press/media: !!Press / Media
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Director General Lea Kauppi selected as one of the top experts for the Horizon Europe
31/07/2019
1 objekt av Mediabevakning
Press/media: !!Press / Media
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iCAN: Finland's precision oncology toolbox
Tomi Mäkelä & Miikka Joojakim Korja
18/04/2019
1 objekt av Mediabevakning
Press/media: !!Press / Media
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Digital health to support precision cancer medicine in iCAN – a new Academy of Finland flagship
08/01/2019
1 objekt av Mediabevakning
Press/media: !!Press / Media
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How this Finnish university is producing future medical pioneers
Tomi Mäkelä, Tiina Immonen & Esko Kankuri
11/09/2018
1 objekt av Mediabevakning
Press/media: !!Press / Media