Projekt per år
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
Tomi Mäkelä
- Avdelningen för biokemi och utvecklingsbiologi - professor
- Tomi Mäkelä / Ansvarig forskare
- Helsinki Institute of Life Science HiLIFE - forskningsdirektör
- Doctoral Programme in Integrative Life Science - Handledare för doktorandprogram
Person: HU, U4 Undervisnings- och forskningspersonal
Projekt
- 1 Aktiv
Kinase signaling linking metabolism and growth control
Conversion, U. P. M.
01/01/1996 → …
Projekt: Forskningsprojekt
Publikationer
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
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: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer 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: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer 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: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer 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: Tidskriftsbidrag › Artikel › Vetenskaplig › Peer review
Öppen tillgång
Fil
Aktiviteter
Scientific Reports (Tidskrift)
Tomi Mäkelä (Referentgranskare)6 dec 2010 → …
Aktivitet: Typer för peer review av output och redaktionsarbete › Redaktör för vetenskaplig tidskrift
European Research Council, ERC (Extern organisation)
Tomi Mäkelä (Ordförande)okt 2010 → 31 dec 2013
Aktivitet: Medlemskapstyper › Utlåtanden vid tillsättning
Univ Helsinki, Faculty of Medicine (Extern organisation)
Tomi Mäkelä (Ordförande)3 jun 2010
Aktivitet: Medlemskapstyper › Medlemskap 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 evenemang › Public Talks
The Cold Spring Harbor Laboratory ‘Epigenetics, Chromatin & Transcription’ meeting
Ying Yang (Poster presentation)maj 2010
Aktivitet: Typer för deltagande i eller organisering av evenemang › Arrangemang av och deltagande i konferens/workshop/kurs/seminarium
Priser
Anders Jahre Young Investigator Award
Tomi Mäkelä (!!Recipient), 1 jan 2005
Pris: Pris och hedersbetygelser
Helsingin Yliopiston Biotieteellisen Tiedekunnan Pro Gradu palkinto 2007
Emilia Kuuluvainen (!!Recipient), 2007
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
Annual Centre of Excellence seminar: Peer review easier in life sciences
14/12/2010
1 Mediabidrag
Press/media: !!Press / Media
Radiaattori: telomeraasista Nobel / Sisko Loikkanen
21/10/2010
1 Mediabidrag
Press/media: !!Press / Media
Tomi Mäkelä Helsingin biotekniikan instituutin johtoon
16/01/2009
1 Mediabidrag
Press/media: !!Press / Media
Science Days Finland 2007: Opportunities from Cancer Biology
10/01/2007
1 Mediabidrag
Press/media: !!Press / Media