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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.

2019 Grantees

Julia Frede, PhD

Julia Frede, PhD

Postdoctoral Fellow
Dana-Farber Cancer Institute
Boston, Massachusetts
Defining the differentiation states of myeloma at single cell resolution

Scientific Statement of Research
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.

Biography
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.

Hijai Regina Shin, PhD

Hijai Regina Shin, PhD

Postdoctoral Scholar
University of California, Berkeley
Berkeley, California
Targeting mTORC1-dependent oncogenic growth

Scientific Statement of Research
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.

Biography
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.

2018 Grantee

Marco Bezzi, PhD

Marco Bezzi, PhD

Postdoctoral Fellow
Beth Israel Deaconess Cancer Center, Harvard Medical School
Boston, Massachusetts
A novel murine platform for genetic driven translational cancer research

Scientific Statement of Research
Next generation sequencing, personalized targeted therapy and immunotherapy have promised to revolutionize cancer therapy. Nevertheless, major hurdles have yet to be overcome in translating this knowledge to the clinic for the majority of patients. Key to evaluating personalized therapeutic approaches is the availability of relevant models that can faithfully mimic the complex nature of patient tumors, its evolution and its microenvironment in an immunocompetent setting. Dr Bezzi proposes the development of a novel platform incorporating an “off-the-shelf” approach that enables a rapid and relatively inexpensive route to modeling the complex heterogeneity of human tumors in mice, which is readily exportable to multiple cancer types. Using a biobank of organoids derived from multiple genetically engineered mouse models, Dr. Bezzi aims to generate a series of combinatorial orthotopic grafts in syngeneic recipients to be used for the simulation of co-clinical trials that will greatly facilitate the realization of precision based approaches in the clinic.

Biography
Dr. Marco Bezzi obtained his BSc and MSc degrees in molecular biotechnologies at the University of Bologna, Italy. In 2010 he was awarded the SINGA scholarship and joined the School of Medicine of the National University of Singapore. During his PhD training Marco studied the role of PRMT5 in development and cancer mentored by Dr. Ernesto Guccione. In 2014 he joined the lab of Dr. Pandolfi at the Beth Israel Deaconess Medical Center (Harvard Medical School) to study prostate cancer genetics and it’s microenvironment. In 2015 he secured a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Research and he is currently working on novel models for translational cancer research.

Acknowledgement of Support
One of the biggest challenges for precision medicine in cancer is the ability to rapidly evaluate patient specific therapies. The AACR Clinical and Translational Cancer Research Fellowship represents an invaluable opportunity to accomplish my research goals successfully by developing novel models to facilitate fast-tracking of personalized treatments from the lab to the clinic.