2017-2018 Duke-UNC Immunotherapy Training Program Postdoctoral Fellows
Miranda Carper, PhD
Mentors: Barbara Savoldo, MD, PhD; Antonio Amelio, PhD
As a researcher, I am passionate about studying the molecular changes that occur during tumorigenesis with an interest towards developing targeted cancer therapies. The incidence of HPV-induced HNSCC is steadily increasing and is currently implicated in approximately 60 percent of all oropharyngeal carcinomas. Unfortunately, patients continue to suffer from high morbidity and mortality due to limited treatment options despite decades of research. While at UNC-CH under the advisement of Antonio Amelio, PhD, I have been characterizing a novel autochthonous genetically engineered mouse model (GEMM) for investigating HPV induced oral cancers since current models do not accurately recapitulate key features of this cancer. Specifically, I developed and validated a novel intra-lingual method of tamoxifen administration to ensure site-directed high-risk HPV16 E6 and E7 expression in the oropharyngeal mucosa using minimal tamoxifen. Currently, our recent discovery of immune cell infiltration by HPV16 E6 and E7 oncoproteins in our GEMM has prompted investigation into the mechanisms of immune suppression in the tumor microenvironment with hopes of developing adoptive T-cell therapies.
Alan Chen, PhD
Mentors: H. Kim Lyerly, MD
My goal is to develop immunotherapies to treat breast cancer. Therapeutic treatment of HER2+ (Human epidermal growth factor receptor 2) breast cancer with anti-HER2 monoclonal antibodies is part of the current standard of care. However, more than half of HER2+ breast cancer patients develop resistance against HER2-targeted antibodies and relapse during their first year. This reality highlights the need for the development of additional therapies. I am interested in the enhancing vaccines to elicit a stronger, more durable immune response against HER2+ tumors through the underutilized MHC-II pathway. I am also interested in exploring the synergisms between vaccination platforms and checkpoint inhibitors as a combinatory treatment for HER2+ breast cancers which have become resistant to the current standard of care immunotherapies.
Nancy Kren, PhD
Mentors: Shelton Earp, MD; Yuliya Pylayeva-Gupta, PhD
My overarching goal is to gain a better understanding of the role that immune response plays in the development and progression of pancreatic cancer. Specifically, I am interested in myeloid cell populations and how they contribute to the overwhelming immunosuppressive tumor microenvironment. Pancreatic tumors, as well as pre-invasive lesions, have significant immune cell infiltration, including tumor-associated macrophages and myeloid-derived suppressor cells (MDSCs), however, effector T-cells are rare. This increase in myeloid populations is associated with the lack of infiltrating effector T-cells. The underlying mechanisms that confer activation of immunosuppressive pathways in these myeloid populations in pancreatic cancer is not well understood. Currently, through a collaboration with the Earp lab, I am investigating how Mer and Tyro receptor tyrosine kinases, on monocytes and MDSCs, contribute to the immunosuppressive phenotype of myeloid cell populations. Mer and Tyro kinases can be activated by apoptotic material and act to polarize macrophages to a M2 or anti-inflammatory phenotype to prevent prolonged or chronic inflammation. In the context of pancreatic cancer, this fail-safe can contribute to the immunosuppressive tumor microenvironment. We are currently interrogating Mer and Tyro receptor tyrosine kinases in pancreatic cancer models utilizing genetic models as well as small molecule inhibitors.
Eben Lichtman, MD
Mentor: Gianpietro Dotti, MD
I am currently in my third year of training in the clinical hematology/oncology fellowship program at the University of North Carolina. My clinical interest is in multiple myeloma, and research interests focus on the development of cellular immunotherapies for patients with hematologic malignancies. In the lab, I work under the mentorship of Gianpietro Dotti, MD, to investigate potential chimeric antigen receptor T-cell based therapies for the treatment of acute myeloid leukemia.
Alex Robeson, PhD
Mentor: Jonathan Serody, MD
My desire as a cancer biologist is to study the complex tumor microenvironment, with the ultimate goal to identify weaknesses and new therapeutic targets. In particular, I study B-cells that infiltrate breast tumors, with a focus on characterizing the B-cell receptor (BCR) repertoire. B-cell infiltration has been correlated with an improved prognosis in some breast cancer subtypes. Based on previous work, we believe that these B-cells have a direct, anti-tumor effect through BCR targeting. By employing single-cell genome and transcriptome sequencing, as well as bioinformatics tools developed by my predecessors, we aim to identify anti-tumor BCRs that can be turned into therapeutic agents as well as tumor-associated antigens that could serve as novel targets. Doing so could have a significant impact for breast cancer patients whose tumors are characterized by infiltrating lymphocytes, as is often the case for basal-like triple-negative tumors.