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.

2023 Grantees

Research

Hormone receptor positive (HR+) breast cancer patients are usually treated with targeted therapies, including CDK4/6 inhibitors. Despite initial encouraging responses, tumors usually become resistant. In addition to intrinsic resistance that tumors develop, tumor-extrinsic factors, such as cancer-associated fibroblasts residing in the tumor microenvironment, also contribute to treatment-resistance. Dr. Hogstrom seeks to elucidate the function of CAF-secreted metabolites in stimulating treatment resistance to CDK4/6 inhibitors in HR+ breast cancer. To accomplish this, she has established a library of patient-derived organoid cultures and matching cancer-associated fibroblasts from primary and metastatic HR+ breast cancer.

Biography

Dr. Hogstrom received her doctorate at University of Helsinki in Finland, where she studied gene regulation in intestinal stem cells and colorectal cancer. After completing her graduate studies, she joined Beth Israel Deaconess Medical Center as a postdoctoral research fellow. Her research focuses on the metabolic interaction between the breast tumor and tumor microenvironment in HR+ breast cancer.

Acknowledgement of Support

“I’m truly honored to receive the AACR-AstraZeneca Breast Cancer Research Fellowship. This fellowship will help me advance my postdoctoral training in understanding how the tumor microenvironment influences treatment resistance and will be invaluable for my transition from a fellow to an independent investigator.”

Research

The risk of developing most cancers increases with age. Despite over 50% of breast cancer patients being over 60 years old, less than 20% of clinical trial enrollees fall in this age bracket. Further, most preclinical work is performed in young mice. Dr. Spasic’s preliminary data demonstrate that triple negative breast cancer (TNBC) progression and response to chemotherapy (paclitaxel) and immune checkpoint blockade (anti-PD-L1) is distinct between immunologically young and aged mice and is driven by age-associated differences in immune cells. Dr. Spasic proposes to use a novel DNA barcoding system to investigate clonal dynamics to uncover tumor intrinsic drivers of age-associated TNBC progression and manipulate interferon gamma signaling to direct immune cell function to improve responses to therapy.

Biography

Dr. Spasic received his undergraduate degree in bioengineering from the University of California, San Diego in 2012. He then completed his doctorate in 2018 in biomedical engineering at Columbia University, where he studied strategies to promote bone regeneration for the treatment of osteoporosis. Currently, Dr. Spasic is a postdoctoral fellow at Brigham and Women’s Hospital. Dr. Spasic’s research focuses on understanding how age impacts the immune system to dictate breast cancer progression and response to therapy.

Acknowledgement of Support

“Through the incredible support of this fellowship, I will have the ability to continue my work understanding how age impacts triple negative breast cancer progression and response to therapy to help us get closer to improving outcomes for all breast cancer patients.”

2022 Grantees

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.

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 master’s degree in public health from the University of Auckland, and his doctoral degree 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.

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 doctoral degree 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.

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.

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 doctoral degree at Paul Sabatier University in Toulouse, France. Her doctoral 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

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 doctoral degree 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.

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.

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.

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

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 Grantee

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.