Research Profile - College of Medicine and Health Science - United ...

Department of Biochemistry
Signal transduction pathways and
disease (Dr. Sehamuddin Galadari)
Cellular homeostasis is dependent upon an array of
intracellular communication pathways. Cells need to
receive signals and send signals, and in that way they
communicate with one another at the molecular level.
This is achieved by an intricate network of enzymatically
regulated biochemical signal pathways prone to
regulation by specific messages. If one or more of these
enzymes are abrogated or over-subscribed, then
disease is set. Indeed, this is what happens at the
molecular level of diseases such as cancer, where
normal cell growth runs out of control, either due to
over subscription of the growth signaling pathway or
under subscription of the cell death signaling pathway,
both of which may occur following deregulated activity
of some enzymes in that pathway, thus leading to
tumor formation. Our research effort is focused on
studying the following:
Sphingolipids, a novel group of putative second
messengers, their putative targets, and the enzymes
that produce them. In particular, our effort is focused
on ceramide, sphingosine, and sphingosine 1-
phosphate, as well as, their targets. This group of
messengers play vital signaling role in apoptosis,
angiogenesis and stress responses.
We are applying the tools of molecular cell biology as
well as classical biochemistry to elucidate the function
of these messengers, the enzymes that generate them,
and their targets.
Ceramide (cer) a pro-death lipid ©
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Phytochemicals, are naturally occurring compounds
that are extracted from fruits, vegetables, and herbs.
Increasingly, evidence is being provided as to their
importance in health. To that end, we are investigating
the effects of different natural products on lipid
signaling pathways involved in diseases such as cancer
and diabetes.
Research Highlights. We have been investigating neutral
ceramidases which regulate the levels of ceramide,
sphingosine, and sphingosine 1-phosphate. Recently,
we have purified the human neutral ceramidase from
human cervical cancer cells and we are currently
characterizing the reverse ceramidase activity of this
enzyme.
Reverse activity of recombinant
neutral ceramidase
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