Profile
Petra Sipilä
Adjunct Professor of Reproductive and Developmental Biology
Director, Turku Center for Disease Modeling
ORCID ID: 0000-0001-8187-7143
Description of Research
Androgens are required for the male reproductive tissues. In addition, androgens regulate gene ex-pression in several non-reproductive tissues. Defects in androgen signaling are linked to diseases, such as prostate cancer. Androgens act through androgen receptor, AR, a hormone-inducible nuclear receptor. Upon ligand binding, AR is shuttled to the nucleus where it binds to the androgen response elements to regulate gene transcription. Specificity of spatiotemporal androgen regulation in different tissues is achieved by differential usage of coregulators. However, in many target tissues the regulation of cell type specific responses to androgen action remains poorly understood. Given the importance of androgen action, it is necessary to understand how androgen actions are normally regulated. We are especially interested in how tissue-specific androgen responses are mediated via AR SUMOylation, pioneer factors, collaborating transcription factors and small RNAs, namely microRNAs in the male reproductive tissues.
We are also part of the FinnDisMice research consortium, that generated disease models for several rare diseases of the Finnish disease heritage. One of the diseases, Cartilage-hair hypoplasia, is manifested by growth disorder and defective immunity. The disease is caused by mutations in a long non-coding RNA, RMRP, the functions of which are poorly known. As a part of the FinnDisMice research consortium, we created a mouse model for Cartilage-hair hypoplasia to improve the understanding of the pathological mechanisms causative for the disease. Our focus is to discover novel functions and interactors of Rmrp in mouse that are translatable to human, ultimately to contribute to the discovery of biomarkers as well as development of diagnostic and therapeutic strategies for Cartilage-hair hypoplasia system.
Representative Publications
Toriseva M, Björkgren I, Junnila A, Mehmood A, Mattsson J, Raimoranta I, Laiho A, Nees M, Elo LL, Poutanen M, Breton S, Sipilä P. Runx transcription factors are essential in maintaining epididymal epithelial differentiation. Cellular and Molecular Life Sciences 2024 Apr 17;81(1):183. doi: 10.1007/s00018-024-05211-5
Zárybnický T, Heikkinen A, Kangas SM, Karikoski M, Martínez-Nieto GA, Salo MH, Uusimaa J, Vuolteenaho R, Hinttala R, Sipilä P, Kuure S. Modeling Rare Human Disorders in Mice: The Finnish Disease Heritage. Cells 2021, 10, 3158. https://doi.org/10.3390/cells10113158
Sipilä P, Junnila A, Hakkarainen J, Huhtaniemi R, Mairinoja L, Zhang FP, Strauss L, Ohlsson C, Kotaja N, Huhtaniemi I, Poutanen M. The lack of HSD17B3 in male mice results in disturbed Leydig cell maturation and endocrine imbalance akin to humans with HSD17B3 deficiency. FASEB J. 2020 May;34(5):6111-6128.
Zhang F-P, Malinen M, Mehmood A, Lehtiniemi T, Jääskeläinen T, Korhonen H, Laiho A, Elo L, Ohlsson C, Kotaja N, Poutanen M, Sipilä P*, Palvimo J.* Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction. Nature Communications 2019 Feb 15;10(1):777, * equal contribution
Wu J, Movérare-Skrtic S, Zhang FP, Koskela A, Tuukkanen J, Palvimo JJ, Sipilä P, Poutanen M, Ohlsson C. Androgen receptor SUMOylation regulates bone mass in male mice. Mol Cell Endocrinol. 2018 Sep 24. pii: S0303-7207(18)30278-8
Huhtaniemi R, Oksala R, Knuuttila M, Mehmood A, Aho E, Laajala TD, Aittokallio T, Laiho A, Elo L, Ohlsson C, Kallio P, Mäkelä S, Mustonen MVJ, Sipilä P, Poutanen M. Adrenals contribute to growth of castration-resistant VCaP prostate cancer xenografts. Am J Pathol. 2018 Dec;188(12):2890-2901.
Knuuttila M, Mehmood A, Mäki-Jouppila J, Ryberg H, Taimen P, Knaapila J, Ettala O, Boström PJ, Ohlsson C, Venäläinen MS, Laiho A, Elo LL, Sipilä P, Mäkelä SI, Poutanen M. Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer. Endocrine-Related Cancer 2018 25:807-819.
Hakkarainen J, Zhang F-P, Cisneros Montalvo S, Nurmio M, Toppari J, Ohlsson C, Kotaja N, Sipilä P, Poutanen M. Hydroxysteroid (17β) dehydrogenase 1 expressed by Sertoli cells contributes to steroid synthesis and is required for male fertility. FASEB J Jan 24:fj201700921R. doi: 10.1096/fj.201700921R
Knuuttila M, Mehmood A, Huhtaniemi R, Häkkinen MR, Oksala R, Laajala TD, Ryberg H, Handelsman DJ, Aittokallio T, Auriola S, Ohlsson C, Laiho A, Elo LL, Sipilä P, Mäkelä SI, Poutanen M. Antiandrogens reduce intratumoral androgen concentrations and induce androgen receptor expression in castration-resistant prostate cancer xenografts. Am J Pathol. 2018 Jan;188(1):216-228.
Björkgren I, Alvarez L, Blank N, Balbach M, Turunen H, Laajala TD, Toivanen J, Krutskikh A, Wahlberg N, Huhtaniemi I, Poutanen M, Wachten D, Sipilä P. Targeted inactivation of the mouse epididymal beta-defensin 41 alters sperm flagellar beat pattern and zona pellucida binding. Mol Cell Endocrinol. 2016 May 15;427:143-54.
Björkgren I, Gylling H, Turunen H, Huhtaniemi I, Strauss L, Poutanen M and Sipilä P. Imbalanced lipid homeostasis in the conditional Dicer1 knock-out mouse epididymis causes instability of the sperm membrane. FASEB J, 2014 29:433-42
Björkgren I, Saastamoinen L, Krutskikh A, Huhtaniemi I, Poutanen M and Sipilä P. Dicer1 ablation in the mouse epididymis causes dedifferentiation of the epithelium and imbalance in sex steroid signaling. PLoS One, 2012 7(6):e38457