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 and to establish a successful career path in this field.
Chronic lymphocytic leukemia (CLL) is a paradigmatic model of cancer evolution – having a long stable phase, spontaneously regressing, and then progressing to an aggressive disease, or even transforming into aggressive mature B-cell lymphoma. Although large-scale genomic/epigenomic studies have revealed the complex genomic alterations of the disease, the available information remains insufficient to explain the influence of genomic/epigenomic changes in CLL progression and transformation. Dr. Nadeu is set to decode the complex evolutionary paths of CLL through an integrative genomic/transcriptomic/epigenomic analysis of sequential tumor samples from a selected cohort of patients.
Dr. Nadeu received his PhD in biomedicine from the University of Barcelona. He has contributed to a better understanding of the heterogeneous genomic landscape of chronic lymphocytic leukemia and its influence on patient outcomes. He has also been involved in the identification of novel non-coding driver mutations, the (epi)genomic characterization of mantle cell lymphoma, the use of cell-free DNA for the genomic profiling of diffuse large B-cell lymphoma, and the development of new bioinformatic algorithms to characterize B cell tumors from next-generation sequencing data.
Acknowledgment of Support
I am deeply honored to be awarded the 2021 AACR-Amgen Fellowship in Clinical/ Translational Cancer Research. My most sincere gratitude to the AACR, Amgen, and its scientific review committee. This award boosts my postdoctoral fellowship, setting the path towards an independent scientific career. I hope the results of this project will translate into better management strategies for patients.
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. Dr. Thangavadivel is using next generation sequencing methods to identify mutational status and epigenetic changes in chronic lymphocytic leukemia (CLL) cells which will help distinguish specific clones and understand their biological differences. She is also investigating 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.
Dr. Thangavadivel obtained her PhD at the Medical University Innsbruck, Austria. 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. Later, she joined the Experimental Hematology Laboratory at The Ohio State University, where she is currently working on mutational, epigenetic, and biochemical features of tumor cells along with the surrounding bone marrow microenvironment in 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 that remains incurable despite recent advances in treatment. It has been suggested that immature differentiation states correlate with therapy resistance in myeloma. Dr. Frede aims to define therapeutic approaches that can overcome therapy resistance by delineating changes in functional states which can be targeted. She is performing RNA sequencing of single myeloma cells in longitudinal samples from patients with relapsed/refractory myeloma to analyze differentiation state changes. She is investigating 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.
Dr. Frede obtained her PhD 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 Dana-Farber Cancer Institute, supported by a fellowship from the German Research Foundation. She is investigating the 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. 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. Dr. Shin is using small-molecules that disrupt critical protein-protein interactions (PPIs) required for mTORC1 activation to investigate mTORC1 regulation.
Dr. Shin received her PhD in the School of Biological Sciences at Seoul National University. Her PhD work focused on the epigenetic and transcriptional regulation of autophagy. She is currently a postdoctoral fellow at the University of California, Berkeley, where she works on mTORC1 regulation and on nutrient sensing mechanisms by the lysosomes.
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.