Med Student Grants Fund Constance Shreckengost's Melanoma Research

February 2018

Constance Shreckengost, PhD, a fourth-year medical student applying for residency in general surgery and recent graduate of the Emory Graduate Neuroscience Program, has received the American Skin Association's Hambrick Medical Student Grant Targeting Melanoma and Skin Cancer and the Melanoma Research Foundation's Medical Student Research Grant. Both awards will be used to fund investigations she will conduct with her mentor and Emory surgical oncologist Michael Lowe, MD, of the effects of obesity and skin stress signaling on melanoma.

"While obesity contributes to 14-20 percent of cancer deaths in the United States, the interaction between obesity and melanoma is vaguely understood," says Dr. Shreckengost. "Obesity is known to dysregulate the body's internal, central stress response system, and could also affect melanoma progression by disrupting the skin stress response process."

Skin is persistently subjected to multiple internal and external stressors, and has developed its own neuroendocrine responses to these stimuli. Increased expression of these skin stress signaling factors is linked to melanoma tumor progression. Primarily, Dr. Shreckengost explains, skin stress signaling appears to stimulate the MAPK pathway, a cellular communication system involving a receptor's signal on the surface of a cell traveling to the DNA in the cell's nucleus. The MAPK pathway can promote tumor growth, and components of this pathway are often found in cancer cells.

"The MAPK pathway is constitutively activated in 80 percent of all melanoma," she says. "Inhibiting components of the MAPK pathway has been shown to improve melanoma-specific survival, but resistance to this therapy remains a major barrier. We believe that obesity alters the stress response system in melanoma in a manner that subverts the positive response to MAPK inhibition."

With the aim of enhancing knowledge of treatment response mechanisms and to identify novel therapy targets for combatting melanoma, Dr. Shreckengost's primary investigative method will be to combine retrospective chart reviews with immunohistochemical and gene expression assays to assess obesity's influence on stress signaling and the response to targeted therapies in melanoma.