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The overall theme of the research in my laboratory is
twofold: [1] analyzing the molecular and cellular mechanism responsible for
trafficking gene products from their site of synthesis to their site of
action during organelle biosynthesis using the melanocytes as a model
system, and [2] understanding pathological processes underlying various
pigmentary diseases (i.e., albinism, vitiligo, melasma, post-inflammatory
pigmentation, etc.). Current
specific projects in the laboratory include the following.
Illustration to the left demonstrates the biogenesis
of the melanosomes (i.e., Stages 1-4) in the perinuclear Golgi zone of the
melanocyte.
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1] The Hermansky-Pudlak Syndrome (HPS) is a
congenital, potentially fatal, multi-system disorder presenting with
oculocutaneous albinism, a mild to severe bleeding diathesis, and ceroid
storage disease. These characteristics
result from aberrations in a specific group of cellular organelles, (i.e., the
pigment granules of the melanocyte, the dense bodies of the platelet, and the
lysosome/residual body of the reticular cell respectively). To date, six genes, HPS1, ADTB3A, and
HPS3-6 are associated with HPS.
While ADTB3A codes for the b3A subunit of
adaptor complex-3, the functions of the HPS, and 3-6 gene products
remain unknown. It is hypothesized that
the genes affected in HPS putatively regulate specific molecular steps in the
trafficking of Golgi derived cargo proteins to a target organelle common in the
cell types affected. We are currently
characterizing the role of HPS in the regulation of this cellular pathway.
(This research is funded by NIH.)
 
Illustration on left is a schematic
diagram of the pathway from the Golgi to the melanosome that involves the
HPS-1 & 2 gene products. The
image on the right is a confocal microscope image of cultured melanocytes
stained for expression of Tyrp-1 (green) and the beta subunit of adaptin 3
(red).
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2] Vitiligo
is an acquired cutaneous disease in which the melanocyte component of the skin
is destroyed, resulting in amelanotic lesions of variable size and extent. As a health consequence, the white lesions of
the skin become immunocompromised and also become susceptible to cancer. The etiology of vitiligo consists of multiple
factors including genetic, cytotoxic,
and autoimmune components. The current
prevailing hypothesis is that some inducing agent triggers the genetically
susceptible “vitiligo” melanocytes into an autolytic process. Subsequently, an auto immune response
develops in the patient that appears to exacerbate the disease. We are currently characterizing the etiology
of this disease that affects 1% of the human population worldwide. (This research is funded by NIH and the
National Vitiligo Foundation.)
 
Illustration on the left is an electron micrograph of the
interfollicular epidermis of control skin demonstrating a dendritic
melanocyte integrated among basal keratinocytes. Illustration on the right is a light
microscopic image of melanocytes established in culture using pigmented
skin biopsied from a non-lesional site of an individual with vitiligo.
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3] Skin complexion
color is important to ones self image and is considered an indicator of
physical health. Complex determinants are involved human skin pigmentation. In
this respect, epidermal melanocytes synthesize pigmented melanosomes that are
eventually transferred to and retained by keratinocytes. The resulting skin
color is determined by a combination of the extent of pigment production by
melanocytes and the efficiency of receipt and processing of melanosomes by
keratinocytes. The former process has been thoroughly investigated, defining
the role of major enzymes in the melanization pathway. In contrast, little is
known about intercellular melanosome transfer.
We are currently characterizing the molecular mechanism regulating this
unique transfer process. (This research
is funded by industry.)
 
Illustration on the left is a schematic diagram
representing melanosome transfer from the melanocytes to the epidermal
keratinocyte. The pair of images on
the right represent fluorescently labeled melanocytes co-cultured with
keratinocytes for three days demonstrating the transfer of labeled
melanosomes from the melanocytes to neighboring keratinocytes (arrows)
under fluorescent (left) and differential interference contrast (right)
microscopy.
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More About Dr. Boissy
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