蜜桃影像

Dr. Stephen Munroe蜜桃影像

MilwaukeeWI53201United States of America

Emeritus Professor

Faculty 1978-2013

Dr. Stephen Munroe was an active member of the Department of Biological Sciences鈥� faculty from 1978-2013. The Munroe Laboratory made significant advancements in study of RNA with its many, often surprising roles in the cell. 

Stephen majored in chemistry as an undergraduate.  For graduate work he went to Indiana University, where there was a well-established biochemistry program within the Department of Chemistry.  However, his interests quickly turned to molecular biology as he studied the biosynthesis of tubulin on polysomes isolated from rat brain.  This marked the beginning of his career-long interests in RNA and RNA protein complexes. Following completion of his Ph.D., Munroe spent three years at the Genetics Division of Children鈥檚 Hospital Medical Center in Boston, studying changes in chromatin structure associated with DNA replication, a fascinating problem in light of the recent discovery of nucleosome structure.  A final post-doctoral year at the Worcester Foundation for Biomedical Research outside Boston provided an opportunity to study RNA-protein interactions associated nuclear RNA, a timely undertaking that coincided with the unexpected discovery in 1977 of mRNA splicing  in adenovirus-infected cells.  With the encouragement of his post-doctoral mentor,  Dr. Thoru Pederson, Munroe devoted the last several months of his post-doctoral work to learning methods for isolating nuclear ribonucleoprotein complexes associated with adenovirus RNA.  So it was with stocks of virus and HeLa cell cultures packed in dry ice that he arrived at 蜜桃影像 on a very hot Labor Day weekend in 1978.   

The timeliness of the project Munroe brought with him to 蜜桃影像 led to early funding by the NIH and later the NSF.  Munroe was joined in the lab by several graduate students: Michael Banker, Cynthia Mengle and Mark Maffitt who help develop various molecular methods for characterizing RNA-protein interactions in the cell nucleus.  Another associate of Munroe at this time  was Deborah Meuler, a graduate of 蜜桃影像 who had recently completed her Ph.D. at Indiana University .  Together Munroe and Mueler succeed in establishing the in vitro cell-free system for splicing radiolabeled RNA, recently pioneered by Adrian Krainer while working with Dr. Thomas Maniatis at Harvard.  Munroe used this system to study structural requirements for splicing of adenovirus mRNA with the addition of a complementary antisense RNA. These experiments had two interesting results: first the antisense RNA complementary to exons proved to be an efficient inhibitor of splicing suggesting that exon sequences as well as those at splice sites themselves were critical for splicing.  The additional observation that proteins within the nuclear extract, including those associated with nuclear pre-mRNA, rapidly catalyzes RNA-RNA base pairing also proved very interesting and was the precursor to studies in many other laboratories on RNA chaperones. Both observations were expanded during a year-long sabbatical at Cold Spring Harbor where he worked closely with Adrian Krainer and Richard Roberts, one of the original discoverers of mRNA splicing (and in 1993 a recipient of the Nobel Prize in Medicine).   

On returning to 蜜桃影像, Munroe continued this work with Xiaofan Dong, a graduate student who received a MS degree for her work on protein-catalyzed RNA-RNA annealing.  At the same time he began to investigate the role of naturally occurring antisense mRNAs associated with the expression of mRNA for the thyroid hormone receptor (TR伪)  and Rev-erb伪, the latter a nuclear receptor protein discovered by Dr. Mitchell A. Lazar in Dr. William W. Chin鈥檚 laboratory at Harvard.  Munroe and Lazar thus began a collaboration that has extended to the present time.  Major contributions to this work were made by Michelle L. Hastings and Hema Ingle, two graduate students.  On receiving her Ph.D., Michelle joined Krainer鈥檚 lab at Cold Spring Harbor, where Munroe had worked a decade before.  After a long and productive stay in the Krainer lab, Michelle returned to the Midwest to establish her own, very active lab at Rosalind Franklin University in North Chicago, not far from Milwaukee.   

Other graduate and undergraduate students have since contributed to the study of splicing and antisense RNA.  These include Valerie Salato who now works at Medical College of Wisconsin and Chao Zhang as well as undergraduates Brandon Rindfleisch and Michael Scott Brown who spent two years characterizing TR伪/Reverb伪 expression in marsupial mammals. This evolutionary approach was recently extended by Chris Morales and Cynthia Aguilar, who help sequence these genes in the platypus. 

Another line of work includes collaboration with Dr. Jun Zhu, another former associate of Adrian Krainer, who Munroe worked with during a sabbatical year in Dr. George Church鈥檚 lab at Harvard.  Zhu and Munroe investigated the expression of antisense RNAs throughout the genome using a custom-designed microarray.  These genome-wide investigations with Dr. Zhu, now at the NIH, has recently led to a three-way collaboration with Dr. James  Anderson鈥檚 laboratory. Anderson鈥檚 pioneering work at 蜜桃影像 on RNA-turnover via the TRAMP complex in yeast has provided novels insights into the metabolism of non-coding RNAs.    

Munroe鈥檚 interests in RNA and RNA-protein interactions are reflected in his regular participation in the annual meetings of the RNA Society.  This meeting frequently include a number of 蜜桃影像 graduates, not least Dr. Cindy L. Will, a native of Milwaukee who has worked on the mechanism of mRNA splicing in Germany for many years.  Cindy was an undergraduate majoring in Biology at 蜜桃影像 when Munroe first arrived in Milwaukee.  Recent meetings have included a number of other former 蜜桃影像 biology students: Dr. Frank Rigo, now a researcher at Isis Pharmaceuticals, a biotech company specializing in the developmental of antisense therapeutics, as well as Will Mueller and Megan Meyer, graduate students at U.California-Irvine and Johns Hopkins, respectively. 

Members of the RNA Society often refer to the RNA World, both as a hypothetical step in the evolution of life on Earth and as an association of 鈥渞ibo-philes,鈥� scientists who enjoy the study of RNA in its many, often surprising roles in the cell.