Assistant Professor of Biochemistry & Molecular Biology
PO Box 980614
Richmond, VA 23298-0614
Email: jroesser@hsc.vcu.edu
Telephone: 804-628-1944
Education
- Ph.D. (Chemistry), University of Virginia, 1986
- B.S. (Chemistry), Rensselaer Polytechnic Institute, 1982
Post-Doc
- Department of Pharmacology, Stanford University, 1989-1993
- Department of Biological Sciences, Stanford University, 1986-1989
Research
Most eukaryotic genes contain non-coding, intervening
sequences which must be spliced out of the pre-mRNAs
to produce mature, functional mRNAs. Many pre-mRNAs
in higher eukaryotes can be spliced in alternative
ways to produce two or more different mRNAs, which
can in turn be translated into distinct polypeptide
products. Alternative RNA splicing has been shown
to modulate gene expression in both a developmental
and tissue-specific manner. We are using the calcitonin/CGRP
gene as a model gene to study the mechanisms that
regulate tissue-specific patterns of alternative
mRNA processing. The mammalian calcitonin/CGRP gene
transcript is alternatively spliced in a tissue-specific
manner resulting in the production of mRNA containing
exons 1-4 (calcitonin mRNA) in thyroid C cells and
mRNA consisting of exons 1-3,5 and 6 CGRP mRNA) in
neurons. We are using biochemical and molecular biological
techniques to isolate the genes encoding neuron-specific
regulators of calcitonin/CGRP splicing. This will
permit us to study the mechanism of calcitonin splice
regulation and to determine if there are related
splice regulators present in different cell types.
Neurofibromatosis type 1 (CF1) is an inherited disorder
caused by mutations in the NF1 gene. NF1 has also been
shown to be a tumor suppressor gene, as disruption
of both copies of NF1 has been observed in tumors from
non-NF1 patients. The NF1 protein product, neurofibromin,
contains a region that shares a high degree of sequence
homology with ras GTPase activating protein (p120 GAP)
and like p120 GAP, this NF1 gap-related domain (NF1-GRD)
is capable of regulating p21 RAS. The NF1 pre-mRNA
is alternatively spliced to produce two types of neurofibromin
that differ by the inclusion or exclusion of a 21 amino
acid exon in the NF1-GRD. Most cells make both types
of neurofibromin but changes in the ratio of neurofibromins
produced in a cell has been correlated with cell differentiation
and transformation. Thus, proper control of alternative
splicing of the NF1 transcript is important for normal
cellular functioning. We intend to define the elements
in the NF1 pre-mRNA that control its alternative splicing
and will attempt to identify transacting regulators
of NF1 alternative splicing.
Publications
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