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Laurie B. Cook, Ph.D.
Research Interests
My research interests can be best summarized as a desire to understand the cellular mechanisms involved in the regulation of endocrine signaling as it relates to cancer and disease. G protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane proteins and regulate a wide variety of biological processes that include sensory perception, cardiovascular, immune and endocrine responses. Compromising mutations in GPCRs are responsible for diseases that include nephrogenic diabetes insipidus and retinitis pigmentosa. The goal of my laboratory is to further the understanding of G protein-coupled receptor processing, trafficking, signaling, and degradation so that novel pharmacological targets and treatments can be identified.
Melanin-concentrating hormone (MCH) was initially discovered as a hormone
that induces skin lightening in teleost fish many years ago. MCH does
this by causing the aggregation of melanophores in skin cells towards
the inner parts of the cell. In mammals, however, MCH seems to play
a much more complicated role in appetite suppression and energy expenditure
via receptors localized to different regions of the brain. Humans carry
two receptors for MCH. Mice lacking MCH receptor 1 seem to be somewhat
protected from diet-induced obesity. This makes the MCH receptor a possible
target for anti-obesity medication and, therefore, it is actively being
pursued by numerous pharmaceutical companies.
Little is known about how the two receptors, MCHR1 and MCHR2, are regulated
by cells. GPCRs typically undergo desensitization following agonist
binding in order to prevent aberrant signaling and overstimulation of
the cell. This process generally involves phosphorylation of the receptor,
recruitment of beta-arrestin and internalization of the receptor-agonist
complex. Desensitization may also involve degradation of the receptor.
Resensitization of cells may take minutes or hours, depending upon the
method of receptor renewal. The MCH receptors are known to transmit
signals to downstream G proteins, however signal desensitization and
receptor trafficking are poorly understood. Additionally, cytoskeletal
changes must take place in order for these events to take place. We
are interested in determining the molecules responsible for cytoskeletal
remodeling in response to MCH. In my laboratory, we will use biochemical
methods and fluorescence microscopy to address these issues using a
tissue culture model system.
