Faculty and Research Interests
Randy Strich, PhD
Science Center 354
University of Illinois at Urbana, IL
PhD (Microbiology) , 1986
University of Illinois at Urbana, IL
MS (Microbiology) , 1983
University of Pennsylvania, PA
BA (Biology) , 1980
Our research focuses on two main questions. First, many current anti-cancer drug strategies attempt to generate sufficient cellular damage to induce programmed cell death (PCD). However, many pathways that trigger PCD utilize p53, which is mutated in over half of the tumors examined. Therefore, it is important to identify new strategies by which to attack this problem. Our results revealed that cyclin C is previously unknown PCD inducer in both yeast and mammalian systems. Unlike other cyclin-Cdk kinases, cyclin C-Cdk8 does not control cell cycle progression. Rather, cyclin C and Cdk8 are transcription factors. However, we have discovered a new role for cyclin C in mediating stress-induced mitochondrial fission and PCD independent of Cdk8. Our current research is focused on understanding how cyclin C controls PCD and how this activity can be manipulated to aid in killing cancer cells. We have expanded these studies into in vivo mouse tumor models. These studies indicate that loss of cyclin C function greatly increases tumor formation in a thyroid cancer model dramatically reducing life span of the affected animals. Our ability to jump back and forth between the yeast and mammalian systems provides an exciting platform to elucidate the role cyclin C plays in both mitochondrial fission and PCD.
Our second area of research is directed toward understanding the switch between mitotic cell division and meiotic differentiation in the budding yeast. Meiosis is a specialized, highly conserved process designed to redistribute the genetic material and produce haploid cells capable of sexual reproduction. My laboratory investigates two important questions in controlling meiotic development. First, we are investigating the molecular switch between mitosis and meiosis to determine how the cell executes this change in cell fate. Our work analyzes the targeted destruction of transcriptional repressors required for meiotic gene transcription. This degradation is triggered by a novel signal that includes acetylation of the repressor which makes it a substrate for the anaphase promoting complex ubiquitin ligase. In addition, we are examining the interplay between transcription factor regulation and chromatin remodeling enzymes that mediate the transient transcription expression profiles observed during meiosis.
SELECTED RECENT PUBLICATIONS
1. Bourbon, H.M., et al., A Unified Nomenclature for Protein Subunits of Mediator Complexes Linking Transcriptional Regulators to RNA Polymerase II. Mol Cell, 2004. 14(5): p. 553-7. PMID: 15175151
2. Dimitrova, I., G.G. Toby, E. Tili, R. Strich, S.C. Kampranis, and A.M. Makris, Expression of Bax in yeast affects not only the mitochondria but also vacuolar integrity and intracellular protein traffic. FEBS Lett, 2004. 566(1-3): p. 100-4. PMID: 15147876
3. Strich, R., Meiotic DNA replication. Curr Top Dev Biol, 2004. 61: p. 29-60. PMID: 15350396
4. Strich, R., M.J. Mallory, M. Jarnik, and K.F. Cooper, Cyclin B-cdk activity stimulates meiotic rereplication in budding yeast. Genetics, 2004. 167(4): p. 1621-8. PMID: 15342503
5. Krasley, E., K.F. Cooper, M.J. Mallory, R. Dunbrack, and R. Strich, Regulation of the oxidative stress response through Slt2p-dependent destruction of cyclin C in Saccharomyces cerevisiae. Genetics, 2006. 172(3): p. 1477-86. PMID: 16387872
6. Mallory, M.J., K.F. Cooper, and R. Strich, Meiosis-specific destruction of the Ume6p repressor by the Cdc20-directed APC/C. Mol Cell, 2007. 27(6): p. 951-61. PMID: 17889668
7. Cooper, K.F., M.J. Mallory, V. Guacci, K. Lowe, and R. Strich, Pds1p is required for meiotic recombination and prophase I progression in Saccharomyces cerevisiae. Genetics, 2009. 181(1): p. 65-79. PMID: 19001291
9. Mallory, M.J., M.J. Law, L.E. Buckingham, and R. Strich, The Sin3p PAH domains provide separate functions repressing meiotic gene transcription in Saccharomyces cerevisiae. Eukaryot Cell, 2010. 9(12): p. 1835-44. PMID: 20971827
10. Cooper, K.F. and R. Strich, Meiotic control of the APC/C: similarities & differences from mitosis. Cell Div, 2011. 6(1): p. 16. PMID: 21806783
11. Cooper, K.F., M.S. Scarnati, E. Krasley, M.J. Mallory, C. Jin, M.J. Law, and R. Strich, Oxidative-stress-induced nuclear to cytoplasmic relocalization is required for Not4-dependent cyclin C destruction. J Cell Sci, 2012. 125 p. 1015-26. PMID: 22421358
12. Mallory, M.J., M.J. Law, D.E. Sterner, S.L. Berger, and R. Strich, Gcn5p-dependent acetylation induces degradation of the meiotic transcriptional repressor Ume6p. Mol Biol Cell, 2012. 23(9): p. 1609-17. PMID: 22438583
13. Jin, C., A.V. Parshin, I. Daly, R. Strich, and K.F. Cooper, The cell wall sensors Mtl1, Wsc1, and Mid2 are required for stress-induced nuclear to cytoplasmic translocation of cyclin C and programmed cell death in yeast. Oxid Med Cell Longev, 2013. 2013: p. 320823. PMID: 24260614
14. Law, M.J., M.J. Mallory, R.L. Dunbrack, Jr., and R. Strich, Acetylation of the transcriptional repressor Ume6p allows efficient promoter release and timely induction of the meiotic transient transcription program in yeast. Mol Cell Biol, 2014. 34: p. 631-642. PMID: 24298021
15. Tan, G.S., R. Lewandowski, M.J. Mallory, R. Strich, and K.F. Cooper, Mutually dependent degradation of Ama1p and Cdc20p terminates APC/C ubiquitin ligase activity at the completion of meiotic development in yeast. Cell Div, 2013. 8(9): p. 1-12. PMID: 23816140
16. Cooper, K.F., S. Khakhina, S.K. Kim, and R. Strich, Stress-Induced Nuclear-to-Cytoplasmic Translocation of Cyclin C Promotes Mitochondrial Fission in Yeast. Dev Cell, 2014. 28: p. 161-173. PMID: 24439911
Highlighted in Dev Cell, Volume 28, Issue 2, 112-114, 27 January 2014 “Cyclin C: An Inducer of Mitochondrial Division Hidden in the Nucleus” by Yoshihiro Adachi and Hiromi Sesaki.
Also was featured as Editors Choice in Science Signaling 2014, Vol.7 page-ec33 “Cyclin C Moves Out of the Nucleus” by VanHook, A.M.
17. Jin, C., R. Strich, and K.F. Cooper, Slt2p phosphorylation is required for the stress-induced cytoplasmic translocation and destruction of the yeast transcriptional repressor cyclin C. Mol Biol Cell, 2014. In Press. PMID: 24554767