Continuing from a childhood of electronics, programming and taking things apart to investigate their internal workings, Professor Taipale began his scientific career at the University of Helsinki, Finland; completing a Masters’ degree in biochemistry and subsequent Ph.D. in the Department of Virology, under the supervision of Dr Jorma Keski-Oja. For his doctoral thesis Professor Taipale investigated transforming growth factor β (TGF-β), finding that its inactive form associates with the extracellular matrix to maintain correct localisation of the protein against rapid flow of blood and tissue fluids1-2.
Following a Research Fellowship with Dr Kari Alitalo at the Laboratory of Molecular and Cancer Biology, University of Helsinki, Professor Taipale moved to Johns Hopkins University to study mechanisms of Hedgehog signal transduction in the laboratory of Dr Philip Beachy. Here, Professor Taipale’s work established that the steroidal alkaloid Cyclopamine inhibits the Hedgehog signalling pathway downstream of the tumor suppressor Patched and the oncogene Smoothened3. Several anticancer agents (such as vismodegib and sonidegib) have now been developed to target this pathway.
Since 2003, Professor Taipale has headed an independent research laboratory utilising high-throughput screening, and computational and experimental techniques, to study the role of transcriptional regulation of gene expression in development and growth. His group has developed several methods for probing the “second genetic code”, consisting of transcription factor binding specificities and the combinatorial manner by which transcription factor binding sites are assembled to form tissue-specific enhancer elements. This has allowed Professor Taipale’s group to determine high-resolution binding specificities of human, mouse and Drosophila transcription factors, and the binding mechanisms of transcription factor pairs to DNA4-7. Not only has this work had a major influence on the field of transcription and contributed to annotation of the regulatory genome, but it has also revealed the presence of multiple tissue-specific enhancers in mouse c-Myc and N-Myc genes8-9; a finding with broad implications for growth control and cancer biology.
Professor Taipale joins us in the Biochemistry Department to continue his work on transcriptional regulation; specifically, to understand how DNA sequences determine where and when genes are expressed via the binding of transcription factors:
"Our understanding of the regulation of gene expression is very conceptual and at a high level of abstraction. It’s equivalent to knowing that Spanish is composed of letters and words, and that Spanish sentences have an object, a subject, a verb, and so on. My conceptual understanding of the Spanish language is therefore very good, as is our understanding of the regulation of a few specific genes, but I cannot speak a word of Spanish. What we’re trying to do for gene expression is work out the lexicon and the grammar. This cannot be done by studying a few specific genes; it’s fundamentally a systems-level problem, which requires systems biology and global approaches to solve."
Understanding the lexicon and grammar of gene expression will support the Taipale group in their second systems-level research area of elucidating control of tissue and organism growth, which is likely to be found in gene regulatory elements. Combined, Professor Taipale’s research will impact on both our fundamental understanding of the regulation of gene expression, and on our knowledge of the mechanisms controlling cell growth during normal development and in pathologies such as cancer.
The Herchel Smith Professorship of Biochemistry is one of two established Professorships within the Biochemistry Department. It is funded from a generous bequest by the eponymous organic chemist, and inventor of the contraceptive pill, to support research in fields of biochemistry.
1Taipale et al., J. Biol. Chem.267:25378, 1992.
2Taipale and Keski-Oja, FASEB J. 11:51, 1997.
3Taipale et al., Nature406:1005, 2000.
4Hallikas et al., Cell124:47, 2006.
5Jolma et al., Cell 152:327, 2013.
6Jolma et al., Nature527:384, 2015.
7Yin et al., Science356:eaaj2239, 2017.
8Hallikas et al., Cell152:327, 2006.
9Sur et al., Science338:1360, 2012.