• PO BOX 56 (Viikinkaari 9), 4006

    University of Helsinki

    Finland

Organisationsprofil

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.

Internationellt och inhemskt samarbete Publikationer och projekt inom de senaste fem åren.

Personer

Projekt

Kinase signaling linking metabolism and growth control

Conversion, U. P. M.

01/01/1996 → …

Projekt: Forskningsprojekt

Publikationer

  • 30 Artikel
  • 1 Översiktsartikel
  • 1 Doktorsavhandling

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: TidskriftsbidragArtikelVetenskapligPeer 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, I : Molecular and Cellular Biology. 38, 12, 15 s., UNSP e00573-17.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Öppen tillgång
Fil

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 maj 2018, I : PLoS One. 13, 5, 20 s., 0196986.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Öppen tillgång
Fil

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, I : Journal of Clinical Investigation. 128, 1, s. 402-414 13 s.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Öppen tillgång

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, I : Journal of Cell Biology. 216, 4, s. 1107-1121 15 s.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Öppen tillgång
Fil

Aktiviteter

Scientific Reports (Tidskrift)

Tomi Mäkelä (Referentgranskare)
6 dec 2010 → …

Aktivitet: Typer för peer review av output och redaktionsarbeteRedaktör för vetenskaplig tidskrift

European Research Council, ERC (Extern organisation)

Tomi Mäkelä (Ordförande)
okt 201031 dec 2013

Aktivitet: MedlemskapstyperUtlåtanden vid tillsättning

Univ Helsinki, Faculty of Medicine (Extern organisation)

Tomi Mäkelä (Ordförande)
3 jun 2010

Aktivitet: MedlemskapstyperMedlemskap eller annan role i inhemsk/internationell kommitté, råd, styrelse

Studia Medicina

Tomi Mäkelä (Närvarande)
27 jan 2010

Aktivitet: Typer för deltagande i eller organisering av evenemangPublic Talks

The Cold Spring Harbor Laboratory ‘Epigenetics, Chromatin & Transcription’ meeting

Ying Yang (Poster presentation)
maj 2010

Aktivitet: Typer för deltagande i eller organisering av evenemangArrangemang av och deltagande i konferens/workshop/kurs/seminarium

Priser

Anders Jahre Young Investigator Award

Tomi Mäkelä (!!Recipient), 1 jan 2005

Pris: Pris och hedersbetygelser

Membeship of the Finnish Academy of Science and Letters

Tomi Mäkelä (!!Recipient), 2002

Pris: Pris och hedersbetygelser

The1st prize for the poster, GSBM 2008 annual graduate student meeting

Ying Yang (!!Recipient), 2008

Pris: Pris och hedersbetygelser

Tidningsurklipp

Radiaattori: telomeraasista Nobel / Sisko Loikkanen

Tomi Mäkelä

21/10/2010

1 Mediabidrag

Press/media: !!Press / Media

Tomi Mäkelä Helsingin biotekniikan instituutin johtoon

Tomi Mäkelä

16/01/2009

1 Mediabidrag

Press/media: !!Press / Media

Kiinnostus tutkijan työhön uhkaa hiipua

Tomi Mäkelä

01/01/2009

1 Mediabidrag

Press/media: !!Press / Media

Science Days Finland 2007: Opportunities from Cancer Biology

Tomi Mäkelä

10/01/2007

1 Mediabidrag

Press/media: !!Press / Media