Biological Sciences
Gary A. Bulla, Ph.D.
Current Research Interests
Links to Courses
Bio1001- Biological Principles and Issues
Bio1100-General Biology
Bio2001G-Human Physiology
Bio3101-Molec/Cell/ lab
Bio4751- Advanced Molecular and Cellular Biology 
Laboratory Group
Research Interests
Research opportunities
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1) Activation and silencing of hepatic gene expression. I have used
a) hepatoma variant cell lines derived via selection schemes and b) liver
x fibroblast cell hybrids (a remarkable phenotype in which global and
complete, yet reversible shut-down of liver-specific gene expression
is observed). My lab has shown that two liver-enriched factors are
components of a transcriptional activation cascade that controls the
activation of numerous liver-specific genes. We have also shown that
these transcription factors are absent in hepatoma variant cells and
somatic cell hybrids. In hepatoma variants (but not somatic cell
hybrids), reintroduction of liver-enriched factors fully reactivates
hepatic gene expression. We are currently interested in cloning a
gene from a locus present on human chromosome 12 which appears
to drive global hepatic gene expression.

2) The link between hepatic gene expression and cellular response
to signaling molecules.We have recently reported that cells selected
for loss of hepatic gene expression are uniquely sensitive to
undergoing apoptosis in response to lipopolysaccharide, a phenotype
which can be reversed by genetic rescue experiments. We are
currently studying the mechanism of LPS-mediated apoptosis and
the influence of tissue-type on response to inflammatory
mechanisms (including NF-kB induction).

3) Hepatic transcription factors and Maturity Onset Diabetes of the
Young (MODY). My most recent pursuit involves understanding the
role of liver-enriched factors (HNF1a, HNF1b, and HNF4) on
development of type 2 diabetes, a major world-wide problem. Each of
these genes is identified as a genetic disease locus in certain
diabetic patients. Approximately 45 distinct mutations have been
reported in HNF1a and glucokinase genes, while only 6 and 2
mutations have been identified in HNF4 and HNF1b genes mutations,
respectively. While a large number of mutations have been identified,
the functional relevance of these the majority of these mutations has
not been assessed. It is likely that these defects contribute both to
defective insulin production by islet cells and to development of
insulin resistance in peripheral tissues.
We are employing a recent a recent technology, protein transduction,
to introduce wild-type and mutant forms of these factors into
hepatoma variant cells as well as into insulinoma cells. We will
determine 1) activation of endogenous gene expression 2) glucose
response 3) and insulin response. These studies include the use
genome microarrays to identify altered gene expression caused by
specific mutations. These studies will provide a basis for rationale
drug development