Education:

1988 — 1992
B.S. University of Dayton, Dayton, Ohio

1993 — 1998
Ph.D. University of Toledo, Toledo, Ohio

1999 — 2005
Postdoctoral Fellow, Cold Spring Harbor Laboratory, New York

Research projects:
Research in the Bubulya laboratory is aimed toward understanding the relationship between nuclear structure and gene expression.  The nucleus of mammalian cells is divided into many compartments that play vital roles in cellular processes such as DNA replication and repair, pre-messenger RNA synthesis and processing, and ribosomal RNA synthesis, processing and ribosome assembly.  Nuclear compartments are much different from those found in the cytoplasm, because nuclear compartments are not membrane-bound.  We would therefore like to learn more about the mechanisms that regulate structural maintenance of nuclear domains as well as the functions of individual components of these domains.
Our current focus is to understand the structure and function of nuclear speckles.  Proteomic analysis of purified nuclear speckles showed that these domains contain proteins involved in pre-mRNA processing (Saitoh, et al., 2004).  Excitingly, 32 novel proteins were identified in nuclear speckles and remain to be further characterized with regard to their nuclear functions.  The major project in the laboratory is to determine the role of newly identified nuclear speckle proteins in messenger RNA metabolism (for example, pre-mRNA transcription, pre-mRNA splicing, mRNA transport, and mRNA stability).  The functions of two very interesting proteins, Btf and son, are currently under investigation.  A very intriguing aspect of Btf is it’s unique localization pattern.  Btf is enriched near the periphery of nuclear speckles, where actively transcribed genes are located.  We would like to understand if Btf either activates or represses transcription, or if it is involved in pre-mRNA splicing.  Btf also exhibits interesting localization patterns through the cell cycle, and we would like to understand what controls these changes in cellular localization.  Son is a very large protein with multiple repetitive domains that have not been identified in any other proteins.  This feature suggests that son serves a unique role in cells.  We predict that son may be a scaffolding protein that could serve as a docking site for assembly and regulation of transcription or splicing complexes in nuclear speckles or at transcription sites.
Another research project in the lab is to understand how nuclear speckles are assembled following mitosis.  As cells enter mitosis, all nuclear structures such as the nuclear speckles are disassembled, and their constituents are distributed diffusely in the cytoplasm.  At metaphase, nuclear speckle components begin to assemble in the cytoplasm into MIGs (mitotic interchromatin granule clusters), then the components enter daughter nuclei in telophase.  Interestingly, the two different families of splicing factors (SR proteins and snRNPs) are initially targeted to separate regions of the daughter nuclei, but eventually colocalize in nuclear speckles when they assemble in G1 (Bubulya et al., 2004).  We would like to understand the molecular basis for this initial sorting of splicing factors in daughter nuclei, and how regulatory protein kinases and protein phosphatases are involved in nuclear speckle assembly.

Research Opportunities for Students

If you are a WSU student who is seeking laboratory experience, there are often projects available in the Bubulya lab for undergraduates as well as Master’s and Ph.D. level graduate students.  Students in the BMS Ph.D. program should contact Dr. Paula Bubulya regarding short-term projects that can be completed during a single laboratory rotation.  Students who join the lab will learn cell biology and molecular biology techniques.  Common techniques used in the lab include PCR, DNA subcloning, cell culture, transfection, immunofluorescence, fluorescence in-situ hybridization, immunoprecipitation, and protein purification. Students with exceptional skills and/or research commitment will co-author research manuscripts and present data at lab meetings as well as national meetings (e.g. American Society for Cell Biology meetings, Cold Spring Harbor Laboratory meetings).

Publications:
Bubulya P. A., K. V. Prasanth, T. J. Deerinck, D. Gerlich, J. Beaudouin, M. H. Ellisman, J. Ellenberg and D. L. Spector.  2004.  Hypophosphorylated SR splicing factors transiently localize around active nucleolar organizing regions in telophase daughter nuclei.  J. Cell Biol. 67:51-63.

Saitoh, N., C. S. Spahr, S. Patterson, P. Bubulya, A. F. Neuwald and D. L. Spector.  2004.  Proteomic analysis of interchromatin granule clusters. Mol. Biol. Cell.  15:3876-3890.

Bubulya P. A. and D. L. Spector. 2004.  “On the move”ments of nuclear components in living cells.  Exp. Cell Research.  296:4-11.

Prasanth K. V., P. A. Sacco-Bubulya, S. G. Prasanth and D. L. Spector. 2003. Sequential
entry of components of the gene expression machinery into daughter nuclei.  Mol. Biol. Cell.  14:1043-1057.

Sacco-Bubulya P. A. and D. L. Spector. 2002. Disassembly of interchromatin granule
clusters alters the coordination of transcription and pre-mRNA splicing.  J. Cell Biol. 156:425-436.

Wahl J.K., J. E. Nieset , P. A. Sacco-Bubulya, T. M. Sadler , K. R. Johnson and M. J. Wheelock. 2000. The amino- and carboxyl-terminal tails of b-catenin reduce its affinity for desmoglein 2.  J. Cell Sci. 113: 1737-45.