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AACR-Cancer Research UK Transatlantic Fellowship

The AACR-Cancer Research UK Transatlantic Fellowship is a four-year postdoctoral fellowship program to support promising early-stage postdoctoral researchers to pursue their projects both in the U.K. and the U.S. It represents a joint effort from the AACR and CRUK to support exceptional investigators interested in beginning their independent postdoctoral research careers.

2019 Grantees

Geylani Can, PhD

Geylani Can, PhD

Postdoctoral Fellow
Harvard Medical School
Boston, Massachusetts
Regulation of DNA replication in mitosis

Research
DNA must be rapidly and accurately duplicated before each cell division. Failure during replication leads to genomic instability which is a major source of many diseases including cancer. Importantly, the duplication of certain ‘difficultto-replicate’ loci such as common fragile sites (CFS) is often not completed until mitosis, and this delay can have detrimental consequences. In fact, CFSs are among the most commonly rearranged genomic loci in cancer genomes, highlighting a causal connection between cancer and late DNA replication. It remains unclear how cells mitigate damage associated with late replication in mitosis. By using an unbiased proteomics approach as well as candidate screening, Dr. Can aims to discover new factors that are required for the regulation of DNA replication in mitosis. The newly identified factors will be analyzed biochemically to reveal their roles in genomic rearrangement at CFSs. Understanding the regulation of DNA replication in mitosis may uncover new targets for anticancer therapies.

Biography
Dr. Can is a postdoctoral fellow in Dr. Johannes Walter’s laboratory at Harvard Medical School. He is currently studying the regulation of DNA replication in mitosis. Dr. Can earned his BS in molecular biology and genetics at the Izmir Institute of Technology, Turkey, and completed his MS thesis at the Karolinska Institute, Sweden. He then joined the Gurdon Institute, University of Cambridge, and in 2018, obtained his PhD investigating the roles of DNA damage checkpoint during the cell cycle.

Acknowledgment of Support
The 2019 AACR-Cancer Research UK Transatlantic Fellowship will be of tremendous help to realize my ambitions at this early stage of my career development. I feel very grateful to have received this prestigious fellowship and the opportunities that open up to me as a consequence. I am excited to pursue my research on DNA replication in mitosis, and I hope that it will allow me to contribute to advances in cancer treatment in the coming years.

Alejandro Jimenez-Sanchez, PhD

Alejandro Jimenez-Sanchez, PhD

Postdoctoral Research Fellow
Memorial Sloan Kettering Cancer Center
New York, New York
Integrative single cell time-series for tumor microenvironment remodeling

Research
Immunotherapy has revolutionized cancer treatment by targeting tumor-immune interactions and providing durable objective responses in advanced metastatic cancers. However, these therapies have only been effective in a subset of cancer types and patients. Thus, strategies to enhance T-cell infiltration and tumor recognition are needed to potentiate immunotherapy. Single-cell genomics makes it possible to disentangle heterotypic cellular interactions in tumors and reveal mechanisms of response to therapies in an unprecedented manner. Dr. Jimenez-Sanchez is using these approaches to characterize the response to a combination of senescence-inducing therapy and anti-PD1 immunotherapy in lung and pancreatic adenocarcinomas. He is developing computational methods that integrate single-cell transcriptome, epigenome, T-cell receptor profiling, and spatial transcriptomics data across space and time. He will model the tumor microenvironment and tumor evolutionary dynamics in response to senescence-inducing and immunotherapy treatments using tractable mouse models and single-cell data from hundreds of human lung and pancreas tumor samples.

Biography
Dr. Jimenez-Sanchez received his doctorate at the University of Cambridge, where he used genomics approaches to study the microenvironment of ovarian tumors. He detected pervasive heterogeneity in immune infiltrates within patients and found evidence of oncogenic signaling associated with immune exclusion. He then joined Dr. Dana Pe’er’s group at the Sloan Kettering Institute in New York, and Professor Charles Swanton’s group at the Francis Crick Institute in London, to study tumor spatio-temporal dynamics in response to immune-combination therapies using single-cell genomics computational methods. Dr. Jimenez-Sanchez’s aim is to unleash the potential of the immune system to fight cancer.

Acknowledgment of Support
I am grateful for the support that the AACR-Cancer Research UK Transatlantic Fellowship is providing for my postdoctoral research. This fellowship is allowing me to bring together the expertise of two world leaders of cancer research into this exciting project and it will be critical for my scientific career development.

Ching Ting (Justin) Loke, BM BCh, PhD

Ching Ting (Justin) Loke, BM BCh, PhD

Research Fellow
University of Birmingham
Birmingham, United Kingdom
Understanding the clonal structure and chemoresistance of ASXL1/RUNX1 AML

Research
The major cause of treatment failure in AML is disease relapse. Genomic profiling of AML patients has shown that mutations in ASXL1 commonly co-occur with RUNX1 mutations, which renders these patients at an increased risk of induction failure and relapse. It is unclear as to why the two mutations co-occur and why they are resistant to treatment. Using samples from patients with these mutations, we will identify the clonal structure of the disease at different timepoints of the disease trajectory. We will also develop a new mouse model of this disease to enable identification of mechanisms of collaboration and novel vulnerabilities of this form of AML. As well as advancing our understanding of the basic biology of this disease, this project will potentially have implications on how we monitor patients with these mutations after therapy and how we treat these patients.

Biography
Dr. Loke trained at the University of Cambridge and the University of Oxford Medical School. and then completed postgraduate hematology training in Birmingham, United Kingdom. His interest is in Acute Myeloid Leukemia (AML). Dr. Loke completed his PhD at the University of Birmingham and was awarded a number of prizes for his studies of the epigenetic deregulation of AML with RUNX1 translocations under Professor Constanze Bonifer. Dr. Loke is currently working at the Queen Elizabeth Hospital and the CRUK Clinical Trials Unit in Birmingham. and is involved in the management of trials involving patients with AML undergoing allogeneic stem cell transplants.

Acknowledgment of Support
This fellowship is vital to my development as a clinician scientist with the aim to develop transformative strategies to help patients with AML. This funding scheme is unique in enabling this transatlantic collaboration which will accelerate research in a number of hematology-oncology research centers internationally.

Hadley Elizabeth Sheppard, PhD

Hadley Elizabeth Sheppard, PhD

Postdoctoral Fellow
The Institute of Cancer Research
London, United Kingdom
Drugging brachyury in chordoma

Research
Dr. Sheppard’s project aims to drug brachyury and its genetic regulation in chordoma. Chordoma is a rare primary tumor that develops in the skull base and spine and currently has no targeted therapies. Strong evidence supports the hypothesis that chordoma is driven by expression of the T gene, which encodes the protein brachyury. Dr. Sheppard’s proposed research in chordoma is reflected in three aims to: 1) investigate the underlying basis of brachyury dependency in chordoma, 2) advance therapeutic targeting of brachyury using clinical grade transcriptional CDK inhibitors, and 3) develop direct small molecule degraders of brachyury. Progress along these thematically linked aims will advance biological understanding of chordoma and accelerate needed targeted therapies towards the clinic.

Biography
Dr. Sheppard completed her undergraduate education at the University of California, Davis, and received her PhD in genetics and genomics in the laboratory of Dr. Charles Lin at Baylor College of Medicine. During her PhD studies, Dr. Sheppard was part of the team that mapped a super enhancer regulating T (brachyury) in chordoma. With this finding, she investigated the selectivity of transcriptional CDK inhibitors that act via super enhancers to disrupt master transcription factors like brachyury. Dr. Sheppard is looking forward to continuing her postdoctoral work in chordoma from an increasingly translational perspective in the laboratory of Dr. Paul Workman at the Institute of Cancer Research.

Acknowledgment of Support
I am thrilled to receive this fellowship as it facilitates my ability to work in the laboratory of Dr. Paul Workman at the Institute of Cancer Research. With this funding, I will conduct impactful chordoma research that will directly benefit patients while enhancing a collaborative chordoma U.K. research network.