The Joanna M. Nicolay Melanoma Foundation (JMNMF) presented Amanpreet Kaur, a student in the Wistar/University of the Sciences Cancer Biology Ph.D. program, with one of ten, nationally competitive, 2013 “Research Scholar Awards” (RSA). The $10,000 grants support exceptional graduate student melanoma research and also provide distinction to lab directors, universities and cancer research institutions across the U.S.
Kaur, who studies in the laboratory of her mentor, Wistar Assistant Professor Ashani Weeraratna, Ph.D., will use the money to further her work on protein receptors that play an important role in melanoma progression and therapy resistance.
According to HMNMF, The 2013 RSA applicant pool grew to include 44 of the country’s most promising young melanoma researchers, and 28 prominent cancer centers, eight as first-time participating institutions. As first in the U.S. to fund graduate student melanoma researchers, the JMNMF program is celebrating the program’s seventh anniversary. The Research Scholar Award program was initially piloted with the Johns Hopkins Sidney Kimmel Cancer Center in 2006, and expanded nationally to benefit the broader academic, scientific, clinical and patient communities and encourage larger numbers of students to choose melanoma research as their professional career path. To date 146 students and 47 cancer research centers are distinguished through their active involvement in this nationally-renowned program.
According to Regina Shannon Bodnar, JMNMF Chair, “Our Foundation’s ‘Research Scholar Awards’ are invaluable at the grassroots level, to specifically grow interest in melanoma research, at leading cancer research centers nationwide. If we can attract the brightest young minds, that are considering or are already within the nation’s cancer research pipelines, to pursue a career in melanoma research – we’re that much closer to better understanding the disease, identifying the means for effective treatments and, most importantly, finding a cure for this deadly and increasingly prevalent disease.”
Exploring the Origins of Aggressive Melanoma
Melanoma is the most aggressive form of skin cancer, and metastatic melanoma is largely incurable. Recent discoveries identifying some of the key drivers of melanoma, such as the oncogene BRAF, have led to the development of targeted therapy. However, while these therapies have met with astounding early success, patients often relapse within a few months. Understanding the mechanisms that govern this resistance to BRAF inhibitors is of critical importance.
The Weeraratna laboratory has demonstrated that a signaling pathway, the Wnt signaling pathway, guides the transition of melanoma cells to a highly invasive state. The proteins that initiate the set of changes leading to the increased invasion of melanoma do so by binding to additional proteins known as receptors, which act as a conduit for messages relayed into the cell. These messages may tell a cell how to grow, when to stop growing, when to die, or when to move.
Recently, the Weeraratna laboratory has found that two of these receptors (ROR1 and ROR2) play opposing roles in melanoma. If the receptor ROR1 is present on a melanoma cell, this predicts for a less invasive melanoma, while ROR2 predicts for a highly invasive melanoma. Importantly, they are finding that the mechanisms that guide invasion, may also direct therapy resistance. ROR2, in addition to predicting highly invasive melanoma cells, also drives resistance in these same cells.
The goal of Kaur’s project is to understand how ROR1 and ROR2 communicate with each other, and to determine whether shifting the balance of ROR2 to ROR1 in the cell will sensitize melanoma cells to therapy.
“To achieve this, we will build artificial skin in the lab, in which the levels of these receptors are manipulated using genetic approaches,” said Kaur “We will then test the ability of the current inhibitors to stall the growth of these tumors, and cause them to regress.”
According to Kaur, the expectation is that shifting the balance from ROR2 to ROR1 will increase the sensitivity of the melanoma cells to the inhibitors. This work will allow for the identification of ways to overcome resistance to the available inhibitors, and may also identify alternate targets for therapy.