Hematology / Oncology Research Laboratory
Through Dr. Carl Simon Shelley's research, we expect to not only better understand fundamental biologic principles, but also to identify new therapeutic targets that can be used in the fight against an array of pathologies. The research is aimed at determining the basic molecular mechanisms that control cancer cell adhesion such that therapeutic targets can be developed. Their recent experiments have focused on suppressing a specific protein component of cellular membrane coverings that functions like Teflon. This covering deflects attacks on the cancer by national killer cells, thus allowing the cancer to grow.
From the Researcher
The journal Science published that “adhesion molecules are among the hottest topics in biology and are seen as dynamic contributors to just about everything that happens in the body” (Volume 260, page 906).
Sialophorin (CD43) is a major anti-adhesion molecule on the surface of white blood cells and the β2-integrins (CD11/CD18) are a major family of pro-adhesion molecules. When white blood cells are freely flowing through the body they express low levels of β2-integrins but high levels of sialophorin. This bias towards expression of anti-adhesive forces prevents both homotypic and heterotypic interactions and maintains white blood cells within the circulation.
During wound healing or the fight against infection white blood cells undergo processes of differentiation and/or activation characterized by a repression of sialophorin expression and a concomitant induction of β2-integrin expression. This shift in bias towards expression of pro-adhesive forces facilitates the intercellular contact required to produce effective wound healing or mount an attack against infection.
While changes in sialophorin and β2-integrin expression are critical to the normal defense of the human body, their abnormal activity can be catastrophic. The pathogenesis of a host of diseases and pathologic states is driven by the abnormal adhesion of white blood cells. These conditions include atherosclerosis, diabetes, leukemia, immunodeficiency diseases such as AIDS and the ischemic reperfusion injury that occurs in frost bite, organ transplant, limb reattachment and after a heart attack or stroke. In addition, it has been found that solid tumors, such as lung and colon cancer, have acquired the ability to produce sialophorin that normally should only be expressed by white blood cells. This abnormal production of the anti-adhesion molecule sialophorin likely both protects the tumor from destruction by the innate immune system and also facilitates metastasis by helping to break up the primary neoplastic lesion.
The research we are undertaking is aimed at determining the basic molecular mechanisms that control both the normal physiologic and also the abnormal pathologic expression of sialophorin and the β2-integrins. In this way we expect not only to better understand fundamental biologic principles but also to identify new therapeutic targets that can be used in the fight against an array of pathologies.