Rainer B. Lanz, Ph.D.
Department of Molecular and Cellular Biology
Director MCB Q-PCR, NURSA investigator
Ph.D.: University of Zurich, Switzerland
Postdoctoral training: Baylor College of Medicine, Houston
Develop Strategies for Deciphering the Transcription Complexome
One of the major mechanisms through which eukaryotic cells respond to developmental and environmental signals is by altering patterns of gene expression. By transmitting these signals to transcription factors using complex and tightly regulated processes, the transcriptional coregulators function as essential signaling integrators for the coordinated control of broad gene expression programs. Dysregulation of coregulator signaling circuitry has severe consequences for cell homeostasis and often contributes to pathogenesis.
Transcriptional coregulators function as multi-subunit complexes that exhibit a diversity of enzymatic activities to dynamically modulate transcription. A combinatorial usage of the complex components depends on cell type and state of cell differentiation, response to different signaling pathways and ligands, but also for structural determinants of transcription factor-coregulator and coregulator-complex components interactions on the basis of alternative splicing and post-translational modifications. Currently my interest is focused on NR coregulators, which comprise a heterogeneous and functionally distinct group of molecules (protein and RNA) that associate with nuclear receptors (NR) by direct binding or in a complex with other molecules and integrate cellular signals by tethering varied enzymatic activities to the transcription unit for the purpose of precisely regulating nuclear receptor-mediated target gene expression.
I believe that the appreciation for NR coregulator biology is imperative for a fuller understanding of human disease. We thus have developed strategies for deciphering the NR coregulator complex code. In a multifaceted collaboration with the proteomics strand of NURSA (Nuclear Receptor Signaling Atlas), a discovery-driven trans-NIH consortium with the mission of cataloging NR and their coregulator-related data in health and disease, we are using bioinformatics approaches to de-convolute NR and coregulator functional interactomes identified in native cells through mass-spectrometry. By mining and clustering of primary data and their systematic integration into generic contextual information, we construct probabilistic networks for transcription that ultimately should lead to practical benefits for patients through the development of effective treatments and pharmaceuticals.
- O'Malley BW, Qin J and Lanz RB. (2008). Cracking the coregulator codes. Curr Opin Cell Biol 20:310-5.
- Lanz RB, Lonard DM and O'Malley BW. (2008). Nuclear receptor coregulators in human diseases. In: Nuclear Receptor Coregulators and Human Diseases, eds Kumar R and O’Malley BW. World Scientific March 28:1-133. ISBN 978-981-270-536-5
- Lanz RB, Jericevic Z, Zuercher WJ, Watkins C, Steffen DL, Margolis R and McKenna NJ. (2006). Nuclear Receptor Signaling Atlas (www.nursa.org): hyperlinking the nuclear receptor signaling community. Nucleic Acids Res 34:D221-6.
- Hatchell EC, Colley SM, Beveridge DJ, Epis MR, Stuart LM, Giles KM, Redfern AD, Miles LE, Barker A, MacDonald LM, Arthur PG, Lui JC, Golding JL, McCulloch RK, Metcalf CB, Wilce JA, Wilce MC, Lanz RB, O'Malley BW and Leedman PJ. (2006). SLIRP, a small SRA binding protein, is a nuclear receptor corepressor. Mol Cell 22(5):657-68.
- Vlahopoulos S, Zimmer WE, Jenster G, Belaguli NS, Balk SP, Brinkmann AO, Lanz RB, Zoumpourlis VC and Schwartz RJ. (2005). Recruitment of the androgen receptor via serum response factor facilitates expression of a myogenic gene. J Biol Chem 280(9):7786-92.
- Zhang Z, Burch PE, Cooney AJ, Lanz RB, Pereira FA, Wu J, Gibbs RA, Weinstock G and Wheeler DA. (2004). Genomic analysis of the nuclear receptor family: new insights into structure, regulation, and evolution from the rat genome. Genome Res 14(4):580-90.
- Apostolakis EM, Lanz R and O'Malley BW. (2004). Pituitary adenylate cyclase-activating peptide: a pivotal modulator of steroid-induced reproductive behavior in female rodents. Mol Endocrinol 18(1):173-83.
- Lanz RB, Chua SS, Barron N, Soder BM, DeMayo F and O'Malley BW. (2003). Steroid receptor RNA activator stimulates proliferation as well as apoptosis in vivo. Mol Cell Biol 23(20):7163-76.
- Lanz RB, Razani B, Goldberg AD and O'Malley BW. (2002). Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA). Proc Natl Acad Sci USA 99(25):16081-6.
- Lanz RB, McKenna NJ, Onate SA, Albrecht U, Wong J, Tsai SY, Tsai MJ and O'Malley BW. (1999). A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 97(1):17-27.