AACR-Amgen Fellowships in Clinical/Translational Cancer Research
The AACR-Amgen Fellowships in Clinical/Translational Cancer Research represent a joint effort to encourage and support mentored young investigators to conduct clinical or translational cancer research. Eligibility is limited to postdoctoral and clinical research fellows who have completed their most recent doctoral degree within the past five years. Proposed research projects may be in any area of clinical or translational cancer research.
Ibrutinib has been a transformative therapy for CLL. Most patients who achieve complete remission after treatment with ibrutinib have persistent, low-level disease called minimal residual disease (MRD). These residual cells ultimately are responsible for clinical relapse. The aim of this proposal is to study the changes in CLL cells and the microenvironment, which will help develop strategies to target these residual cells. Dr. Thangavadivel proposes to use next generation sequencing methods to identify mutational status and epigenetic changes in CLL cells which
will help distinguish specific clones and understand biological differences. Dr. Thangavadivel will investigate the changes in the microenvironment and immune cells to understand how MRD cells have altered signaling pathways that enable these cells to escape the effects of ibrutinib. The availability of sensitive and specific methods to quantify residual disease may allow individualized therapy in the future.
Dr. Thangavadivel obtained her PhD at the Medical University Innsbruck, Austria, in 2016. Her PhD work focused on the chemokine network and autophagy mechanism in multiple myeloma. She then spent a year as a postdoctoral fellow at The Lerner Research Institute, Cleveland Clinic Foundation. In 2017, she joined the Experimental Hematology Laboratory at The Ohio State University. Dr. Thangavadivel is currently working on mutational, epigenetic, and biochemical features of tumor cells along with the surrounding bone marrow microenvironment in chronic lymphocytic leukemia (CLL) patients.
Acknowledgment of Support
I am honored and grateful to receive the 2020 AACR-Amgen Fellowship in Clinical/Translational Cancer Research. This award will support my research to identify new strategies to eliminate minimal residual disease in CLL. This fellowship will also promote my career development as an independent researcher in the field of hematologic malignancies.
Multiple myeloma is a bone marrow-derived plasma cell malignancy which remains incurable despite recent advances in treatment. It has been suggested that immature differentiation states correlate with therapy resistance in myeloma. Therefore, a better understanding of cellular plasticity in myeloma is critical. The aim of the proposed research is to define therapeutic approaches that can overcome therapy resistance by delineating changes in functional states which can be targeted. Dr. Frede will perform RNA sequencing of single myeloma cells in longitudinal samples from patients with relapsed/refractory myeloma to analyze differentiation state changes. Dr. Frede will investigate if altered differentiation states are associated with enhancer rewiring and if this epigenetic plasticity can be therapeutically exploited by targeting specific immune markers that are upregulated. The proposed research will provide important insights into lineage plasticity and adaptive state changes at single cell resolution in myeloma and may identify novel therapeutic vulnerabilities.
Dr. Frede currently is a postdoctoral fellow at Dana-Farber Cancer Institute in Boston. She obtained her PhD in the laboratory of Dr. Phil Jones at Cambridge University, UK, where she investigated esophageal cell fate using genetic lineage tracing. Subsequently she spent a year as a research fellow at the Wellcome Sanger Institute, Cambridge, UK. She joined Dr. Lohr’s laboratory at Dana-Farber Cancer Institute in 2016, supported by a fellowship from the German Research Foundation. Dr. Frede currently investigates transcriptional heterogeneity in myeloma on a single cell level and its relevance for novel treatment approaches, in particular immunotherapy.
Acknowledgment of Support
The 2019 AACR-Amgen Fellowship in Clinical/Translational Cancer Research will give me the opportunity to pursue my research investigating transcriptional heterogeneity and epigenetic plasticity in myeloma. I am honored to receive this prestigious award and hope that the experience I obtain will allow me to make a significant contribution to the field in the future.
The mechanistic target of Rapamycin complex 1 (mTORC1) is a master regulator of cell growth and proliferation that is activated at the lysosomes in response to nutrients or growth factors. Several lines of evidence have shown that dysregulated mTORC1 is a key contributor to the dysregulated growth and quality control that drive cancer, diabetes, and neurodegenerative diseases, making it an attractive therapeutic target. Of particular interest, aberrant activation of the mTORC1 pathway is common in both Hodgkin (HLs) and many types of B-cell non-Hodgkin lymphomas (NHLs), and is associated with poor prognosis. However, current pharmacological approaches that target mTORC1 kinase activity suffer from major limitations, urging the need for complete and more specific mTORC1 inhibition, which could elicit more promising clinical responses. Dr. Shin proposes to use small-molecules that disrupt critical protein-protein interactions (PPIs) required for mTORC1 activation to investigate its regulatory mechanism on the lysosomes.
Dr. Shin is a postdoctoral fellow in the laboratory of Dr. Roberto Zoncu at the University of California, Berkeley. She received her PhD in the School of Biological Sciences at Seoul National University in 2016. Her PhD work focused on the epigenetic and transcriptional regulation of autophagy. Dr. Shin now works on mTORC1 regulation as well as nutrient sensing mechanisms by the lysosomes to understand their roles in normal versus cancer cells.
Acknowledgement of Support
I am honored to be the recipient of the 2019 AACR-Amgen Fellowship in Clinical/Translational Cancer Research. I would like to thank the fellowship review committee for choosing my proposal and Dr. Roberto Zoncu for his support and guidance. This fellowship will provide tremendous support to my research and promote my career development.