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The Levinson Emerging Scholars Program

Sherry Lee - Molecular, Cellular, and Developmental Biology

Sherry LeeEncouraged by her lab's strong support, Sherry Lee wants to learn more about cancer etiology in order to better understand how it ravages the human body. Thanks to her mentor, Dr. Paul Nghiem, Sherry has realized that a career in medicine is truly gratifying not when a physician simply prescribes readily available drugs, but when a physician can propose and test a more effective therapeutic treatment. Currently, Sherry is investigating the functional relevance and role of microRNA gene regulation in a deadly form of skin cancer called Merkel cell carcinoma. As a Mary Gates Research Scholar and a Levinson Scholar, Sherry hopes to rely on her family's, her lab's, and the foundations' support to achieve beyond their expectations. Overall, her undergraduate research experience has led her on a promising path to pursue a career in translational medicine. She plans to attend a Medical Scientist Training Program after graduation to continue biomedical research.

Mentor: Paul Nghiem, Medicine-Dermatology and Pathology

Project Title: A Merkel cell polyomavirus-encoded microRNA expressed in human Merkel cell carcinomar

Abstract: Merkel cell carcinoma (MCC) is a rare but lethal skin cancer that is associated with immune suppression. People immunosuppressed with AIDS are twenty times more likely to get MCC. Merkel cell polyomavirus (MCPyV), an immunogenic virus, causes more than 70% of MCC. However, 90% of MCC patients have no identifiable immune suppression. In this population, MCC tumors proliferate by escaping the immune system, perhaps with the help of MCPyV. One potential mechanism the virus employs to escape the immune system is through microRNAs (miRNAs), small noncoding RNAs that downregulate the expression of genes that might be recognized by host immune system. During the early stage of my research project, I helped to discover a Merkel polyomavirus-encoded miRNA and to quantify expression of the Merkel-miRNA in MCC tumors. The Merkel-miRNA was expressed in strongly virus positive tumors (n= 11) and not expressed in virus negative tumors (n=4). Also, I detected MCPyV DNA in MCC patients' blood samples. Because the Merkel-miRNA was predicted to downregulate lymphocyte genes, I hypothesize that it will be present in the blood. For aim 1, I will test blood samples for Merkel miRNA expression. Furthermore, I used a validated in silico algorithm called TargclScan to predict the Merkel-miRNA's human target genes, which are mostly important for immune functions. For example, the gene PSME3 activates the immunoproteasome, which triggers immune responses. I hypothesize that these target genes will be downregulated in virus positive cells. I will quantify expression of Merkel-miRNA target genes in miRNA-positive cells in aim 2. These two aims are essential components to understanding viral genetic control in MCC pathogenesis.

Specific aims:

  1. Detect Merkel-miRNA in blood samples from MCC patients
  2. Quantify gene and protein expressions of Merkel-miRNA target genes in cell line after transfection with Merkel-miRNA