AACR-AstraZeneca Cancer Research Fellowships

The AACR-AstraZeneca Cancer Research Fellowships represent a joint effort to encourage and support postdoctoral and clinical research fellows to conduct cancer research and to establish a successful career path in this field. Research projects may be basic, translational, clinical, or epidemiological in nature.

2022 Grantees

AACR-AstraZeneca Breast Cancer Research Fellows
Qin Luo, PhD

Qin Luo, PhD

Postdoctoral Associate

Baylor College of Medicine

Houston, Texas

Boosting Immunogenic Cell Death to Enhance Breast Cancer Immunotherapy

Research

Immune checkpoint blockade therapy (ICBT) has relatively limited use in breast cancer patients due to the lack of pre-existing immunity in the tumor microenvironment. Dr. Luo and her colleagues previously found that suppression of RNase activity of endoplasmic reticulum (ER) stress sensor IRE1a by IRE1 inhibitor ORIN1001, in combination with taxane, promotes immunogenic lytic cell death.  In this project, Dr. Luo aims to elucidate how the ORIN1001/taxane combination induces inflammasome-dependent pyroptotic cell death, and to design a mechanism-based novel breast cancer immunotherapeutic strategy.

Biography

Dr. Luo received her PhD at the Institute of Biomedical Sciences (Fudan University, China), where she showed how Neutrophil Extracellular Traps (NETs) and cancer-associated fibroblasts fuel hepatocellular carcinoma (HCC) initiation and metastasis. She is currently a Postdoctoral Associate in the Department of Molecular and Cellular Biology at Baylor College of Medicine. Her long-standing interest has always been in cancer immunology and tumor microenvironment. She seeks to expand her research and training to breast cancer stress responses and immunotherapy, and aims to develop mechanism-based novel therapies to transform metastatic breast cancer into a manageable chronic disease.

Acknowledgement of Support

I am extremely honored to receive the 2022 AACR Breast Cancer Research Fellowship. This provides critical support for me as I seek to uncover the mechanisms behind how ORIN1001 and taxane convert PD-L1-negative immune-cold breast tumors to immune-hot ones. Also, this funding support sets me on the path towards an independent scientific career.

Minh Tung Phung, PhD

Minh Tung Phung, PhD

Postdoctoral Fellow

 The Regents of the University of Michigan

Ann Arbor, Michigan

Early-onset breast cancer and research on the environment

Research

Early-onset breast cancer (EOBC) is the most common cancer among young adult women. The incidence rates of EOBC are higher among Black compared to White individuals, and among people living in urban compared to rural areas. The impact of environmental exposures on EOBC risk is notably understudied. Dr. Phung and his colleagues are set to conduct a population-based case-control study in Michigan to examine the impact of environmental factors on EOBC risk, not only for the general population but also for different groups stratified by race/ethnicity and other social determinants of health. Environmental exposures of interest include personal-level factors (e.g., smoking, and pesticides) and location-related factors (e.g., air pollution, and metals). Given that many exposures are modifiable, this study has tremendous potential to identify EOBC primary prevention opportunities and improve health equity.

Biography

Dr. Phung obtained his MPH from the University of Auckland, and his PhD in epidemiology from the University of Michigan. His masteral thesis work was focused on the development of a risk prediction model for breast cancer survival in New Zealand. In his doctoral training, he formulated a risk stratification model for precision prevention of ovarian cancer. He is currently a postdoctoral fellow at the University of Michigan, where he continues his breast cancer and ovarian cancer research emphases.

Acknowledgment of Support

I am extremely honored to receive the AACR-AstraZeneca Breast Cancer Research Fellowship. This fellowship will advance my research and goal to become an independent researcher in cancer epidemiology. This fellowship will also provide opportunities to build a foundation in research on environmental factors and early-onset breast cancer.

AACR-AstraZeneca Immuno-oncology Research Fellow
Shalom Lerrer, PhD

Shalom Lerrer, PhD

Postdoctoral Research Scientist

Columbia University

New York, New York

Research

Despite the striking success of anti-PD-1/PD-L1 antibodies, most patients do not respond to PD-1 blockade, and many experience immune-related adverse events. Clearly, the need for therapeutics that go beyond interference with ligand binding is critical.  By utilizing mass-spectrometry data and tumor models, the kinase VRK2 was established as a downstream mediator of PD-1. With a long-term goal of developing clinically useful VRK2 inhibitors, Dr. Lerrer is set to define the roles of the kinase domain and protein/protein-interaction domain of VRK2 in mediating PD-1 functions, and uncover the inhibitory roles of VRK2 in different T cell subsets.

Biography

Dr. Lerrer obtained his PhD from the Faculty of Life Sciences of Tel Aviv University, where he studied the inflammatory phenotype and pro-malignant functions of mesenchymal stem/stromal cells (MSC) in the context of the breast tumor microenvironment. Currently a postdoctoral research scientist, he is studying the basic mechanisms underlying PD-1 signaling and functions in T cells, with the anticipation that a better understanding of PD-1 biology will allow for better treatment of cancer patients.

Acknowledgment of Support

My long-term goal is to develop VRK2 inhibitors that will be clinically useful to overcome resistance against current PD1 inhibitors. The AACR-AstraZeneca Immuno-oncology Research Fellowship will allow me to further establish VRK2 as a target, while expanding my skills and knowledge in the field of cancer immunology.

AACR-AstraZeneca Ovarian Cancer Research Fellows
Ksenija Nesic, PhD

Ksenija Nesic, PhD

Research Officer

Walter and Eliza Hall Institute of Medical Research

Parkville, Australia

CRISPR screens to find novel targets to overcome PARP inhibitor resistance

Research

Homologous recombination (HR) DNA repair deficiency is a frequent event in ovarian cancer (OC). While PARP inhibitors (PARPi) are effective targeted drugs for HR-deficient OC, most women eventually stop responding. A comprehensive understanding of mechanisms of PARPi action and resistance are critical to improving outcomes for women with OC. To address this, Dr. Nesic is using genome-wide CRISPR screens to identify both novel PARPi resistance mechanisms and PARPi synergy targets in OC cell line models with different HR defects. Validated screen hits will be explored in vivo using a highly characterized cohort of OC patient-derived xenograft models.

Biography

Dr. Ksenija Nesic graduated with a Bachelor of Science from the University of Melbourne in 2012 and went on to complete a master’s degree with Professor David Thorburn at the Murdoch Children’s Research Institute (Melbourne, Australia), where she developed a sequencing-based test for mitochondrial DNA mutations in children with mitochondrial disease. She completed her PhD in at WEHI (Melbourne, Australia), where she studied diverse mechanisms of PARP inhibitor resistance in ovarian cancer PDX and cell line models. She is continuing this work as a postdoctoral researcher.

Acknowledgment of Support

The AACR-AstraZeneca Ovarian Cancer Research Fellowship is giving me the opportunity to complete fundamental research started during my PhD, that has the potential to improve outcomes for many women diagnosed with ovarian cancer. I am extremely grateful for the support that this fellowship provides, and excited about the research to come.

Anna Salvioni, PharmD, PhD

Anna Salvioni, PharmD, PhD

Postdoctoral Fellow

University Cancer Institute 

Toulouse Oncopole

Toulouse, France

HRD effect on T-cell exhaustion in ovarian cancer

Research

Ovarian cancer is the most lethal gynecologic malignancy. Despite its immunogenic nature, response rates to immune checkpoint blockade monotherapy are low. Patients with Homologous Recombination Deficiency (HRD), whose tumors display higher infiltration by T cells, do not experience a significant response to anti-PD-1 treatment. Dr. Salvioni’s colleagues previously identified two populations of antigen-specific exhausted CD4 and CD8 T cells that play key roles in the response to anti-PD-1 treatment in epithelial malignancies. By characterizing these populations in ovarian cancer samples with different HRD status, Dr. Salvioni aims to elucidate how HRD shapes the immune landscape of tumors.

Biography

Dr. Salvioni completed her Pharmacy training at the University of Padua, Italy, and her PhD at Paul Sabatier University in Toulouse, France. Her PhD research, both in Toulouse and at the University of California Berkeley, as a visiting student, focused on adaptive immunity mechanisms in host-pathogen interactions. She is currently a Postdoctoral Researcher at the University Cancer Institute of Toulouse Oncopole and the Cancer Research Center of Toulouse. She is focused on characterizing the impact of homologous recombination deficiency on T-cell exhaustion in ovarian cancer, laying the groundwork for efficient combination therapies that can help overcome resistance to immunotherapy.

Acknowledgement of Support

I am honored and grateful to be a recipient of the AACR-AstraZeneca Ovarian Cancer Research Fellowship. This grant provides an invaluable opportunity to study the influence of homologous recombination deficiency on T-cell exhaustion in ovarian cancer. This support is pivotal for my path towards being an independent researcher in onco-immunology.

2021 Grantees

AACR-AstraZeneca Breast Cancer Research Fellows
Xue-Yan He, PhD

Xue-Yan He, PhD

Postdoctoral Fellow 
Cold Spring Harbor Laboratory 
Cold Spring Harbor, New York 
Targeting stress-induced neutrophil extracellular traps prevents metastasis 

Research
Emerging evidence has shown a link between chronic stress and tumor metastatic recurrence. Dr. He aims to elucidate how elevated stress hormone glucocorticoids contribute to tumor metastasis via neutrophil extracellular traps (NETs) and how stress-induced NETs influence cancer therapies. To accomplish this, Dr. He is set to 1) use mouse models to determine how stress-triggered NETs promote breast cancer metastasis and 2) uncover how glucocorticoid-induce NETs promote metastasis, using RNA-seq, ChIP-seq, and in vitro screening.

Biography
Dr. He obtained her PhD at the Model Animal Research Center of Nanjing University, where she studied the role of tumor suppressor p53 in the tumor microenvironment. She is currently pursuing postdoctoral studies on breast cancer immune response at the Cancer Center at Cold Spring Harbor Laboratory, with the support of a fellowship awarded by the state of New York. Her goal is to understand how stress promotes breast cancer recurrence via modifying immune response.

Acknowledgment of Support
I am very grateful and greatly honored to be selected for the AACR-AstraZeneca Breast Cancer Research Fellowship. Receiving this fellowship will help advance my postdoctoral training in understanding the mechanisms underlying tumor progression and targeting them for therapeutic benefit and lay a solid foundation for my scientific career development.

Samantha Van Nest, PhD

Samantha Van Nest, PhD

Postdoctoral Associate 
Weill Cornell Medicine 
New York, New York 
The impact of hypoxia on radiation induced anti-cancer immunity 

Research
A profound challenge limiting the success of immunotherapy in breast cancer is the inherently low immunogenicity of this disease. Radiation therapy has been shown at the preclinical level to enhance antitumor immunity by exposing tumor antigens that can be recognized by T cells, converting a previously immune hidden tumor into one that can be systemically targeted. However, breast cancers commonly develop hypoxia, which has been implicated in suppressing antigen processing and presentation. Dr. Van Nest aims to determine how hypoxia modulates radiation’s effects on antitumor immunity.

Biography
Dr. Van Nest has dedicated her career to advancing the next generation of radiation therapy, advocating for personalized and systemic treatment approaches. She obtained her PhD from the University of Victoria, where she established Raman Spectroscopy as a technique for tracking radiobiological responses. She is currently a postdoctoral associate in the Department of Radiation Oncology at Weill Cornell Medicine. Her research operates at the interface between radiobiology and immunology, investigating the impact of radiation on the immunopeptidome and potential exposure of neoantigens to promote anti-tumor immunity

Acknowledgment of Support
It is truly an honor to receive the AACR-AstraZeneca Breast Cancer Research Fellowship and have the opportunity to advance our understanding of the role of hypoxia in radiation induced immunogenicity. It is my hope to provide important rationale for targeting hypoxia in the context of this novel treatment approach.

AACR-AstraZeneca Immuno-oncology Research Fellow
Raphael Mattiuz, PhD

Raphael Mattiuz, PhD

Postdoctoral Fellow 
Icahn School of Medicine at Mount Sinai 
New York, New York 
Determining the regulation and role of mreg DC in tumor immunity

Research
The key steps leading to subversion of the immune system and tumor escape are still obscure. A molecular state of dendritic cells (DCs) upon tumor antigen uptake named “mature DCs enriched in immunoregulatory molecules”’ (mreg DCs) has been recently described. mreg DCs express not only maturation genes associated with T cell stimulation but also genes associated with immunoregulation. Dr. Mattiuz aims to identify molecular drivers of the regulatory module expressed by mreg DCs and to exploit this knowledge to enhance DC immunogenicity and antitumor immunity. In addition, he aims to determine the significance of the spatial distribution of mreg DCs to T cell dependent antitumor immunity.

Biography
Dr. Mattiuz completed his PhD at the Centre d’Immunologie de Marseille-Luminy (Aix-Marseille University, France), where he studied the role of type 1 conventional dendritic cells in breast cancer immunosurveillance He is currently conducting his postdoctoral work at the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, determining the regulation and role of mreg DCs in tumor immunity in mice and patients.

Acknowledgment of Support
It is a great honor to become an AACR-AstraZeneca Immuno-oncology fellow. I am truly grateful to the committee for selecting my research project. It is a crucial step to pursue my research career. I am really looking forward to contributing to the AACR mission by my research in enhancing patient antitumor immunity.

AACR-AstraZeneca Lung Cancer Research Fellow
Joseph Minhow Chan, MD, PhD

Joseph Minhow Chan, MD, PhD

Medical Oncology Fellow 
Memorial Sloan Kettering Cancer Center 
New York, New York 
Uncovering drivers of small cell transformation at single-cell level 

Research
In lung adenocarcinoma (LUAD), neuroendocrine transformation to small cell lung cancer (SCLC) is associated with metastasis and resistance to targeted therapies. Dr. Chan hypothesizes that in the context of RB1/TP53 loss Notch signaling and key transcription factors mediate this neuroendocrine transformation. He is set to 1) leverage scRNA-seq in samples of combined LUAD/SCLC histology to identify molecular markers of subclonal populations and 2) validate predicted transcriptomic drivers of neuroendocrine plasticity in in vitro and in vivo models, including an EGFR+ LUAD patient-derived xenograft that undergoes neuroendocrine transformation after osimertinib treatment.

Biography
Dr. Chan completed his MD/PhD at Columbia University College of Physicians and Surgeons, where he studied computational biology and developed new methods to model the topology of viral evolution and identify recurrent FGFR-TACC fusions in glioblastoma multiforme. He is currently a medical oncology and postdoctoral research fellow at Memorial Sloan Kettering Cancer Center, where he aims to leverage single-cell technologies to understand how neuroendocrine lineage plasticity in lung and prostate cancer mediates metastasis and therapeutic resistance and how the tumor microenvironment can impact this tumor-intrinsic process.

Acknowledgment of Support
I am deeply humbled and grateful to be supported by the 2021 AACR-AstraZeneca Lung Cancer Research Fellowship. I hope this award will provide me with a critical platform to become a successful independent investigator who combines computational biology, single-cell technologies, and translational domain knowledge to create meaningful clinical impact in the lives of my cancer patients.

AACR-AstraZeneca Lymphoma Research Fellow
Joseph G. Schroers-Martin, MD

Joseph G. Schroers-Martin, MD

Postdoctoral Fellow 
Stanford University 
Stanford, California 
Noninvasive early detection & characterization of post-transplant lymphoma 

Research
Patients receiving solid organ transplants are at high risk for cancer, with up to 25% of deaths after heart transplantation due to malignancy. The most common cause of death is post-transplant lymphoproliferative disorder (PTLD), an aggressive lymphoma associated with immunosuppression. There is no established clinical method to screen patients for this cancer. In collaboration with several transplant centers, Dr. Schroers-Martin will use “liquid biopsies” to evaluate early PTLD detection via DNA shed by emerging lymphomas and associated viruses.

Biography
Dr. Schroers-Martin worked as a software developer and pursued bioinformatics and virology training before receiving his medical degree from the University of Hawai’i. He completed internal medicine residency followed by a post-doctoral research year at Stanford University. As a clinical hematology and oncology fellow at Stanford, he utilizes cell-free DNA to study the early detection and biology of lymphomas.

Acknowledgment of Support
The 2021 AACR-AstraZeneca Lymphoma Research Fellowship is a great honor, and I am deeply grateful for this opportunity to continue my work in noninvasive cancer detection and lymphomagenesis. This critical support will provide a foundation for my transition from fellow to independent translational investigator.

2020 Grantees

AACR-AstraZeneca Breast Cancer Research Fellows
Monish Ram Makena, PhD

Monish Ram Makena, PhD

Postdoctoral Research Associate
Johns Hopkins University School of Medicine
Baltimore, Maryland
A novel mechanism of resistance in receptor positive breast cancer

Research
Novel therapeutic strategies are needed for estrogen receptor positive breast cancer patients. Prior work from Dr. Makena’s lab has described a new role for calcium signaling in maintaining genomic integrity in hormone receptor positive breast cancer. They found that the Secretory Pathway Ca2+-ATPase-2 (SPCA2) activates calcium entry into cancer cells. Blocking calcium entry results in ROS accumulation, breakage of one or both strands of DNA, and cell death. In this project, he seeks to understand how SPCA2 regulates the ATM/ATR-p53 DNA damage response pathway, identify the source of ROS, and evaluate the effectiveness of drugs that target this pathway.

Biography
Dr. Makena obtained his PhD from Texas Tech University. Currently, he is a postdoctoral fellow in the Department of Physiology at the Johns Hopkins School of Medicine, where he is exploring a novel link between calcium signaling and breast cancer.

Acknowledgment of Support
This fellowship boosted my confidence, strengthened my professional credentials, and enhanced my motivation to become a translational scientist. Furthermore, this fellowship will cover my salary, and enable me to attend the AACR Annual Meeting, which is a valuable opportunity for a trainee in cancer research.

Naiara Perurena, PhD

Naiara Perurena, PhD

Postdoctoral Research Fellow
Brigham and Women’s Hospital
Boston, Massachusetts
Understanding and combating therapeutic resistance in HER2+ breast cancer

Research
Although many individuals with localized HER2+ breast cancer initially respond to HER2-directed therapies, a subset of patients with no overt signs of metastasis may still relapse. Dr. Perurena aims to define the role of two new tumor and metastasis suppressor RasGAPs in anti-HER2 resistance. The overall goals of the project are to 1) determine how the loss of these proteins precisely promotes resistance to anti-HER2 therapies using in vitro and in vivo models, and 2) identify new targets in these RasGAP-deficient tumors by performing a negative selection CRISPR/Cas9 screen to develop more effective combination therapies.

Biography
Dr. Perurena obtained her PhD at the Center for Applied Medical Research, University of Navarra, where she studied molecular mechanisms of metastasis and received a fellowship to join Cold Spring Harbor Laboratory as a visiting student. Dr. Perurena is a postdoctoral research fellow at Brigham and Women’s Hospital/Harvard Medical School.

Acknowledgment of Support
I am truly honored and grateful to be a recipient of the AACR-AstraZeneca Breast Cancer Research Fellowship. This distinction offers me an extraordinary opportunity to address major challenges in breast cancer treatment and will be invaluable for the development of my scientific career.

AACR-AstraZeneca Immuno-oncology Research Fellows
Maria Casanova-Acebes, PhD

Maria Casanova-Acebes, PhD

Postdoctoral Fellow
Icahn School of Medicine at Mount Sinai
New York, New York
Macrophage determinants of therapy resistance in cancer

Research
There is now a worldwide effort to understand the mechanisms of response and resistance to checkpoint blockade in NSCLC. The contribution of macrophages to immunotherapy is not yet established, but their critical role in tumor biology makes it highly likely that they can influence the response to PD-1 blockade. The goal of this project is to identify novel and relevant macrophage determinants of therapy resistance in lung cancer. By using high dimensional tissue mapping by CyTOF, scRNAseq, and multiplex imaging, Dr. Casanova-Acebes will extensively map human early NSCLC at baseline and in response to PD-1 blockade. She is set to determine the macrophage composition of NSCLC and elucidate how macrophage subsets influence and are influenced by PD-1 immunotherapy.

Biography
Dr. Casanova-Acebes received her PhD in cellular biology and genetics at the Universidad Autónoma de Madrid. She was awarded a fellowship from the Human Frontiers Science Program, one of the most prestigious international grants for postdoctoral researchers. Dr. Casanova-Acebes is studying the contribution of tissue resident and monocyte-derived macrophages in lung adenocarcinoma and ways to manipulate them to harness anti-tumor immunity.

Acknowledgment of Support
I would like to express my very great appreciation to the AACR for granting me an AACR-AstraZeneca Immuno-oncology Research Fellowship. Receiving this grant will help me identify the macrophage determinants that promote therapy resistance. As a soon-to-be principal investigator, this grant will be pivotal in laying the groundwork for my future career in cancer immunology and starting my independent career in the right direction.

Leah Schmidt, PhD

Leah Schmidt, PhD

Postdoctoral Fellow
Fred Hutchinson Cancer Research Center
Seattle, Washington
Elucidating effects of the lung tumor microenvironment on T cell therapy

Research
Immune checkpoint therapy (ICT) is a frontline treatment for lung adenocarcinoma (LUAD); however, ‘non-T cell inflamed’ signatures predict poor responses to ICT in ~50% of patients. Adoptive cellular therapy (ACT) with T cells engineered to express T-cell receptors specific for tumor antigens is an approach that circumvents the need for endogenous T-cell responses. A deeper understanding of the complex interactions between therapeutic cells and the lung tumor microenvironment (TME) will be crucial for developing successful treatment strategies that enhance function and mitigate toxicity. Dr. Schmidt is set to leverage physiologically-relevant preclinical models to probe the role of the evolving TME in shaping ACT outcomes, compare these findings to human LUAD analyses, and uncover prognostic markers and combinatorial strategies to safely enhance ACT efficacy against refractory tumors.

Biography
Dr. Schmidt completed her PhD in biology at the Massachusetts Institute of Technology, where she researched how natural killer cells influence lung cancer progression and how they can be leveraged therapeutically. She is currently conducting her postdoctoral work at the Fred Hutchinson Cancer Research Center, studying the role of the tumor microenvironment in shaping the outcomes of adoptive T-cell therapies.

Acknowledgment of Support
I am proud and grateful to be an AACR-AstraZeneca Immuno-oncology Research Fellowship recipient. In addition to providing crucial financial support during a pivotal and transformative phase in my scientific career, this award offers equally critical professional opportunities to connect and interact as a member of the cancer immunology community of scientists.

AACR-AstraZeneca Lung Cancer Research Fellows
Ezequiel Carlos Dantas, MD, PhD

Ezequiel Carlos Dantas, MD, PhD

Postdoctoral Fellow
Weill Cornell Medical College
New York, New York
Metabolic regulation of lung cancer cachexia by STAT-3

Research
The cancer-associated cachexia syndrome (CACS) is a systemic metabolic syndrome featuring body weight loss due to skeletal muscle and white adipose tissue wasting. In non-small cell lung cancer (NSCLC), approximately 50% and 75% of patients with early and advanced-stage disease, respectively, are affected. Preliminary data from Dr. Dantas’s laboratory suggest that in the LKB1/KRAS (KL) model of lung cancer, cachexia is associated with strong activation of STAT-3 in tumor, liver, and muscle. In this project, he is set to identify the cells and cytokines responsible for the onset of CACS. In addition, he plans to explore whether the JAK2/IRAK1 inhibitor pacritinib can ameliorate CACS by modulating inflammation in the tumor microenvironment while also reducing STAT-3 activation in the periphery.

Biography
Dr. Dantas obtained his MD-PhD from The University of Buenos Aires, where he was awarded the summa cum laude distinction for his studies on the regulation of immune function by extracellular acidosis. In 2017, Dr. Dantas was awarded a prestigious Fulbright Scholarship to study ex-vivo tissue culture techniques at the National Institutes of Health. Dr. Dantas joined Weill Cornell Medical College as a postdoctoral fellow pursuing the development of new clinical strategies for the treatment and early detection of cachexia in lung cancer patients.

Acknowledgment of Support
I would like to express my most sincere gratitude to the AACR selection committee for selecting my proposal for funding. As an early career scientist, this gives me the opportunity to begin the path towards becoming an independent researcher while doing science to improve the lives of patients. I hope that the results of this project will lead to new therapeutic approaches for a pathology that has none.

Shilpa Singh, PhD

Shilpa Singh, PhD

Postdoctoral Fellow
Virginia Commonwealth University School of Medicine
Richmond, Virginia
Novel therapeutic strategy to target lung cancer with p53 mutations

Research
Tumorigenic p53 mutations termed gain-of-function (GOF) p53 mutations are frequently found in all types of human lung cancers. As targeting the mutant p53 protein itself presents technical challenges, preventing expression of downstream GOF p53 transcriptional targets that establish GOF p53 dependency may offer powerful avenues in the development of novel precision therapies. Dr. Singh is set to use a uniquely designed reporter system where expression of mCherry/luciferase genes are driven by a specifically engineered promoter responsive only to GOF p53 and not WT p53. Utilizing this system, she aims to screen chemical libraries to identify inhibitors of GOF p53-mediated transactivation. The chemicals with the ability to inhibit GOF p53-specific transcription will then be used to study the impact on growth and survival of lung cancer cells expressing GOF p53 in in vitro and in vivo assays.

Biography
Dr. Singh received her PhD in biochemistry from Virginia Commonwealth University. Her PhD work focused on investigating contributions of oncogenes (MDM2 and gain of function p53 mutation) in the deregulation of normal or cancer cell proliferation. Currently, she is working on unveiling vulnerabilities of oncogenic mutant p53-driven DNA replication and mitosis in cancer cells in an effort to uncover novel unexplored therapeutic strategies targeting mutant p53-containing lung cancer.

Acknowledgment of Support
I am honored to receive the AACR-AstraZeneca Lung Cancer Research Fellowship. This fellowship will support a project that utilizes the novel observation of dependence of lung cancer cells on endogenously expressing GOF p53 and thus would allow targeting of many lung cancer patients who have cancers with GOF p53.

AACR-AstraZeneca Lymphoma Research Fellows
Zachary Epstein-Peterson, MD

Zachary Epstein-Peterson, MD

Medical Oncology Fellow
Memorial Sloan Kettering Cancer Center
New York, New York
Oncogenic mechanisms and therapeutic targeting of IDH2 mutations in AITL

Research
Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of aggressive malignancies that comprise ~10-15% of non-Hodgkin lymphoma (NHL). Angioimmunoblastic T-cell lymphoma (AITL), one of the most common subtypes of PTCL, exhibits recurrent somatic mutations at arginine 172 (R172) of the metabolic enzyme isocitrate dehydrogenase 2 (IDH2) in 20-30% of patients. Dr. Epstein-Peterson and his research group hypothesize that targeted inhibition of mutant IDH2 may offer an effective new therapeutic strategy to treat IDH2-mutant AITL. To test this hypothesis, they will pursue a series of investigations using primary patient samples and patient-derived xenografts.

Biography
Dr. Epstein-Peterson received his MD from Harvard Medical School. He completed his internal medicine residency at New York Presbyterian Weill Cornell Medical Center followed by chief residency at Memorial Sloan Kettering Cancer Center. He is currently a medical oncology fellow at Memorial Sloan Kettering Cancer Center. Dr. Epstein-Peterson aims to define and target metabolic pathways in lymphoma with a focus on AITL. Additionally, his clinical focus is the care of patients with T-cell and cutaneous lymphomas.

Acknowledgment of Support
I am deeply humbled and honored to receive funding through the 2020 AACR-AstraZeneca Lymphoma Research Fellowship. This fellowship will enable us to pursue investigations that we hope will better define basic disease biology and ultimately translate into better outcomes for patients with T-cell lymphomas. Personally, the fellowship will allow me to develop critical skills as a translational researcher as I transition from fellow to independent faculty investigator.

Timothy J. Voorhees, MD

Timothy J. Voorhees, MD

Hematology and Oncology Fellow
The University of North Carolina School of Medicine
Chapel Hill, North Carolina
Pilot study of anti-PD-1 therapy following CD30 directed CAR-T cell therapy

Research
Hodgkin Lymphoma is a B-cell malignancy characterized by CD30+ multinucleated Reed-Sternberg cells within an extensive, ineffective immune infiltrate. While clinical response rates to CD30.CAR-T therapy in relapsed/refractory Hodgkin lymphoma patients have been high, some patients have developed recurrent disease. These recurring patients have shown promising responses to rechallenge with anti-PD-1 therapy. Dr. Voorhees is set to conduct a prospective pilot study to determine the clinical activity and immunomodulatory effect of rechallenge with anti-PD-1 therapy in patients with relapsed Hodgkin Lymphoma after CD30.CAR-T therapy.

Biography
Dr. Voorhees completed his medical school and internal medicine training at The Ohio State University Wexner Medical Center. He is currently completing his hematology and oncology fellowship at the University of North Carolina. He has been supported by the UNC-Duke Immunotherapy T32 and has been the recipient of several clinical and research achievement awards during his fellowship.

Acknowledgment of Support
I am very honored to be awarded the 2020 AACR-AstraZeneca Lymphoma Research Fellowship. This award will provide essential support to complete my research focusing on anti-PD-1 therapy after CD30.CAR-T therapy in Hodgkin Lymphoma and will provide a strong foundation as I transition from a fellow to an independent investigator

2019 Grantees

AACR-AstraZeneca Breast Cancer Research Fellows
Arvind Panday, PhD

Arvind Panday, PhD

Postdoctoral Fellow
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Therapeutic potential of FANCM for BRCA1-linked breast cancer

Research
Primary cells lacking BRCA1 respond to the Tus/Ter replication fork barrier by forming small tandem duplications (TDs). Breast cancers lacking BRCA1 similarly acquire large numbers of small TDs. Dr. Panday has previously observed that stalled fork motor protein-FANCM (product of the Fanconi anemia [FA] group M gene) acts synergistically with BRCA1 to suppress TDs. He discovered a novel synthetic lethal interaction between BRCA1 and FANCM loss in primary mouse ES cells. He has been dissecting the mechanism of TD formation and homologous recombination at stalled fork using FANCM as a genetic probe and has been determining whether FANCM is an actionable “druggable” target for therapy of BRCA1-linked breast cancer.

Biography
Dr. Panday completed his PhD in biological sciences at the Louisiana State University. During his thesis, he uncovered a novel linker histone-like function of yeast, HMO1. He is a currently a research fellow at Beth Israel Deaconess Medical Center, Harvard Medical School. Dr. Panday’s major goal is to understand the mechanism of genomic instability and associated breast cancer.

Acknowledgment of Support
I am extremely honored to be awarded the AACR Breast Cancer fellowship. I sincerely thank the grant review committee for selecting me as a recipient for this grant. This fellowship will allow me to carry out the proposed research and establish a track record for future grants as I make the critical transition from fellow to independent scientist.

Ariadne Vlahakis, PhD

Ariadne Vlahakis, PhD

Postdoctoral Fellow
University of California, San Francisco
San Francisco, California
NBR1 mediated selective autophagy in pro-metastatic adhesion signaling

Research
Autophagy is a catabolic recycling process that promotes tumor fitness, though the role of selective autophagy during metastasis is unclear. Preliminary evidence has linked the selective autophagy adaptor NBR1 to pro-metastatic signaling events, including focal adhesion turnover, migration, and metastatic colonization. Dr. Vhalakis seeks to elucidate the link between NBR1 mediated selective autophagy and pro-metastatic adhesion signaling in promoting breast cancer metastasis. To achieve this, the proposed research couples cutting-edge proximity-based biotinylation proteomics and human cell biology with in-vivo breast cancer models to 1) dissect the role of selective autophagy in metastatic adhesion signaling, 2) identify novel and cancer-relevant NBR1 targets in human mammary epithelia, and 3) assess the physiological relevance of NBR1 signaling to breast cancer metastasis in-vivo.

Biography
Dr. Vlahakis’s interest in cancer-related cell biology began during her PhD at UC Davis, where she published several first author studies uncovering a novel role for the rapamycin insensitive TOR Complex 2 (TORC2) signaling pathway in promoting autophagy. She is currently a postdoctoral fellow at UCSF, where she focuses on the role of selective autophagy in regulating pro-metastatic adhesion signaling in the context of breast cancer metastasis.

Acknowledgement of Support
Receiving the AACR postdoctoral fellowship fuels within me an immense sense of dedication and honor in continuing my career in cancer research. It significantly poises me for success as I strive to one day become an independent investigator, by providing merit to my dedication and training in cancer research.

AACR-AstraZeneca Immuno-oncology Research Fellows
Brandilyn A. Peters, PhD

Brandilyn A. Peters, PhD

Postdoctoral Fellow
New York University School of Medicine
New York, New York
The lung microbiome, peripheral immunity, and lung cancer recurrence

Research
Eight to thirty-two percent of curatively resected stage I non-small cell lung cancer (NSCLC) patients die within five years of diagnosis, and there is no established method for identifying patients at high risk for recurrence. Dr. Peters aims to relate the lung microbiome to recurrence-free survival and peripheral immune gene expression and to identify lung bacterial biomarkers that can improve the performance of a recurrence prediction model. She hypothesizes that lung bacteria play a role in lung cancer recurrence and that this role is mediated by effects of lung microbiota on the immune environment.

Biography
Dr. Peters received her PhD in environmental health sciences from Columbia University. She subsequently began her postdoctoral training in microbiome research at NYU School of Medicine. As a postdoctoral fellow, Dr. Peters studies the role of the human microbiome in chronic diseases, including cancer.

Acknowledgement of Support
Receiving an AACR-AstraZeneca Immuno-oncology Research Fellowship is a great honor and important step forward in my career. This support will allow me to conduct independent research and develop a successful career in microbiome and cancer research, while enabling me to work towards discovery of microbiome-based approaches to improve cancer survival.

Silvia Pineda, PhD

Silvia Pineda, PhD

Postdoctoral Fellow
Spanish National Cancer Research Center (CNIO)
Madrid, Spain
Exposure factors associated with tumor microenvironment in pancreas cancer

Research
Dr. Pineda is developing analytical methods to integrate molecular and exposure data in pancreatic cancer. Dr. Pineda’s goal is to integrate tumoral immune infiltration features with exposure data (lifestyle, environmental factors, morbidities, and microbiome) to elucidate new factors that affect different subtypes of pancreatic cancer.

Biography
Dr. Pineda earned her PhD with a joint position between the Spanish National Cancer Research Centre (CNIO) and the University of Liege (Belgium), developing and applying advanced statistical techniques in omics integration in bladder cancer. She is currently a postdoctoral fellow at CNIO.

Acknowledgement of Support
It is my distinct honor to receive the 2019 AACR-AstraZeneca Immuno-oncology Research Fellowship. This fellowship will allow me to carry out novel research in data science applied to pancreas cancer and to contribute to the research of this devastating disease. I hope that this prestigious award will help me in becoming an independent scientist in the immuno-oncology field.

AACR-AstraZeneca Lung Cancer Research Fellows
Jayu Jen, PhD

Jayu Jen, PhD

Postdoctoral Fellow
New York University
New York, New York
PIK3C3 is a haploinsufficient tumor suppressor gene in lung cancer

Research
Genomic sequencing of lung adenocarcinoma (LUAD) reveals 47 percent heterozygous deletion of PIK3C3, the gene that encodes the Class III PI3K hVPS34. hVPS34 plays an important role in regulating autophagy, endocytosis, and mTOR, although its potential role in oncogenesis has not been explored. Preliminary results suggest that decreased autophagy mediated by heterozygous mutation or deletion of Pik3c3 promotes lung cancer progression in vitro and in vivo. Moreover, extensive macrophage infiltration was observed in autophagy deficient LUAD, suggesting that impaired autophagy might modulate the LUAD microenvironment. Dr. Jen is determining the underlying mechanism by which Pik3c3 haploinsufficiency promotes lung cancer progression and microenvironment modulation.

Biography
Dr. Jen received her PhD at National Cheng Kung University in Tainan, Taiwan. Her PhD studies focused on transcription dysregulation in lung cancer progression. She joined the NYU Langone Health Perlmutter Cancer Center in New York as a postdoctoral fellow, where she is working on autophagy deficiency-mediated transcription dysregulation and tumor microenvironment in lung cancer.

Acknowledgement of Support
It is my great honor to be selected for a 2019 AACR-AstraZeneca Lung Cancer Research Fellowship. This fellowship will provide support allowing me to complete my current study on autophagy deficiency-mediated lung cancer progression. More importantly, this fellowship will be a solid foundation to build up my academic career.

Catherine Vaughan, PhD

Catherine Vaughan, PhD

Postdoctoral Fellow
Virginia Commonwealth University
Richmond, Virginia
Novel targeting of lung cancer

Research
p53 is mutated in 69 percent of lung cancers; most of these mutations instill gain-of-function (GOF) phenotypes. Unique DNA sequences, referred to as GOF p53 response elements (RE), complex with GOF p53. These REs are needed for GOF p53-mediated transactivation. Dr. Vaughan is exploring the therapeutic potential of using an RE-driven synthetic promoter to specifically express a suicide gene in mutant p53-expressing lung cancer cells.

Biography
Dr. Vaughan completed her PhD in integrated life sciences at the Virginia Commonwealth University (VCU). She is currently a postdoctoral fellow at VCU, where she is exploring unique GOF p53 response elements.

Acknowledgement of Support
I am honored to receive the AACR-AstraZeneca Lung Cancer Research Fellowship. This opportunity supports a project that proposes to design strategies to specifically eliminate cancer cells with gain of function mutant p53. Since p53 is mutated in a large number of lung cancer patients, the impact will be huge.

AACR-AstraZeneca Lymphoma Research Fellows
Chloé B. Steen, PhD

Chloé B. Steen, PhD

Postdoctoral Scholar
Stanford University
Stanford, California
Cellular determinants of adverse risk in follicular lymphoma

Research
Follicular lymphoma (FL) is an indolent lymphoma that is generally considered incurable. Dr. Steen hypothesizes that tumor cellular heterogeneity underlies variation in FL clinical outcomes, including early relapse and transformation. To address this hypothesis, she is using CIBERSORTx to interrogate numerous cell subsets for their associations with early progression and transformation to aggressive disease.

Biography
Dr. Steen completed her PhD work in computational biology on the transcriptomics of transformation in follicular lymphoma at the University of Oslo. As a postdoc at Stanford University, she studies the cellular heterogeneity of lymphomas.

Acknowledgement of Support
Support from the AACR-AstraZeneca Lymphoma Research Fellowship is critical in my development as a young researcher. Hopefully it will also help improve lymphoma patient diagnosis and treatment, as I hope to identify novel drug targets and biomarkers for more personalized medicine.

Soumaya Zlitni, PhD

Soumaya Zlitni, PhD

Postdoctoral Research Scholar
Stanford University
Palo Alto, California
The role of the microbiome in transplant outcomes in lymphoma patients

Research
Lymphoma patients who receive allogeneic hematopoietic stem cell transplantation (HCT) undergo chemotherapy and radiation and are treated with broad-spectrum antibiotics. Loss in gut microbiome diversity is associated with increased risk of graft-vs-host disease. With the increasing appreciation of the role of the gut microbiome in modulating immunity in transplant populations, Dr. Zlitni is identifying novel microbiome-derived immunomodulators from stool extracts from Hodgkin and non-Hodgkin lymphoma patients during the course of their HCT treatment. She will be studying the lead microbes and metabolites further.

Biography
Dr. Zlitni received her PhD in biochemistry from McMaster University in Canada, where her work centered on the discovery and characterization of novel antibacterial inhibitors. Prior to her current postdoctoral work at Stanford, she was a postdoctoral fellow at the University of Toronto, where she studied the metabolic consequences of chemical and genetic perturbations in bacteria and yeast.

Acknowledgement of Support
I am honored to be a recipient of the 2019 AACR-AstraZeneca Lymphoma Research Fellowship. This grant will support me during an important stage of my scientific career. I will pursue critical questions in translational microbiome research with great therapeutic potential to help lymphoma patients who undergo bone marrow transplantation.

AACR-AstraZeneca Ovarian Cancer Research Fellow
Erin George, MD

Erin George, MD

Instructor
University of Pennsylvania
Philadelphia, Pennsylvania
Optimizing DNA damage response inhibitors in Cyclin E high ovarian cancers

Research
Cyclin E (CCNE1) is amplified in 25 percent of ovarian cancers. Aberrant Cyclin E expression increases reliance on ATR and WEE1. Combined inhibition of these kinases (WEE1i-ATRi) is more effective than chemotherapy in preclinical models. Dr. George hypothesizes that sequential treatment of WEE1i-ATRi will be more tolerable and effective than concomitant and response will be Cyclin E level dependent. Thus, she is testing various dosing schedules in PDX models with varying Cyclin E levels, including identifying mechanisms of action for different dosing schedules.

Biography
Dr. George completed her MD and obstetrics and gynecology residency at Columbia University. She finished her gynecologic oncology fellowship and is currently pursuing a career as a physician-scientist at the University of Pennsylvania.

Acknowledgement of Support
My AACR-AstraZeneca Ovarian Cancer Research Fellowship will support the training elements needed to acquire the additional technical expertise, research experience, and publication record to foster a strong foundation to become on independent investigator. I hope to continue translational research and take our promising findings to clinical trials.