AACR-Bristol Myers Squibb Midcareer Female Investigator Grant
The AACR-Bristol Myers Squibb Midcareer Female Investigator Grant represents a joint effort to encourage and support mid-career female physician-scientists and researchers to conduct immuno-oncology research and to foster their career advancement toward becoming a senior investigator. Research projects may be translational or clinical in nature with a focus on immuno-oncology.
The sentinel lymph node sits at the crossroads of metastasis and immune surveillance. While lymphatic transport primes lymph nodes for immune activation, it also progressively installs multiple mechanisms of immune suppression that enable tumor progression. In this project, Dr. Lund and her group will dissect the relationship between the primary tumor, lymphatic transport, and the emergence and maintenance of protective lymph node resident memory T cell populations. She will aim to 1) define the anatomic origin and developmental trajectory of sentinel lymph node resident T cell populations, and 2) determine the impact of lymph node metastasis on their maintenance and function. Finally, she will explore their clinical association with recurrence in sentinel lymph nodes of stage III melanoma patients. A basic understanding of sentinel lymph node biology, paired with an evaluation of interpatient heterogeneity, is expected to reveal new determinants of patient outcome that may inform clinical care.
Dr. Lund received her PhD from Rensselaer Polytechnic Institute in Troy, New York, and completed postdoctoral training at the Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland. She is currently an Associate Professor in the Ronald O. Perelman Department of Dermatology at NYU Grossman School of Medicine in New York. Dr. Lund and colleagues established the paradigm that tumor-associated lymphatic vessel remodeling regulates anti-tumor immune surveillance. Her group aims to understand the basic mechanisms that govern lymphatic/immune interactions to identify translational strategies to tune lymphatic transport and reinvigorate anti-tumor immunity.
Acknowledgment of Support
The AACR-Bristol Myers Squibb Midcareer Female Investigator Grant will accelerate and expand our efforts to understand how lymphatic transport governs immunity and determines risk for progression in melanoma. I am honored to receive this award and continue to support a diverse team of early career researchers towards their own independence.
Dr. Schietinger and her colleagues recently demonstrated that although the dysfunctional state of tumor-infiltrating T cells is initially reversible (plastic), these T cells ultimately progress to an imprinted (fixed) state that is resistant to therapeutic reprogramming. These plastic and fixed dysfunctional T cell states are defined by unique chromatin states and transcription factor networks. In this project, she aims to 1) employ CRISPR-mediated editing approaches to identify and target molecular drivers of T cell dysfunction and 2) identify the phenotypic, functional, and epigenetic states of human tumor-infiltrating T cells. In addition, she plans to test whether surface proteins can be used as biomarkers of the underlying epigenetic programs to predict which patients are likely to benefit from immunotherapeutic interventions.
Dr. Schietinger received her PhD from the University of Chicago and University of Munich, Germany, and conducted her postdoctoral training at the University of Washington. She is currently an associate member of the Immunology Program at Memorial Sloan Kettering Cancer Center. She aims to understand when, why, and how immune cells become unresponsive to tumors. Her lab utilizes genetic cancer mouse models that mimic cancer development in patients to investigate T cell responses over the course of tumor development, and define the molecular and epigenetic mechanisms that are responsible for the failure to control and eliminate tumors.
Acknowledgment of Support
The 2021 AACR-Bristol Myers Squibb Midcareer Female Investigator Grant award will allow us to conduct bold, high-risk high-reward science needed to design transforming immunotherapeutic reprogramming strategies for all cancer patients.
Pancreatic cancer arises through non-invasive precursor lesions that are curable if detected and treated early. One precursor lesion, intraductal papillary mucinous neoplasm (IPMN), is a key target for clinical intervention and can serve as a model for premalignant pancreatic neoplasia. Dr. Wood aims to comprehensively analyze the immune microenvironment in a genomically characterized cohort of IPMNs, allowing correlation of the immune microenvironment with various features of the genomic landscape, including somatic mutations in specific driver genes, tumor mutational burden, and quality and quantity of predicted neoantigens. In addition, she and her research group plan to utilize an organoid model of IPMN to identify tumor infiltrating lymphocytes (TILs) specifically targeting these neoplasms.
Dr. Wood earned both her MD and PhD from Johns Hopkins University School of Medicine. She completed residency in anatomic pathology and a fellowship in gastrointestinal and liver pathology, also at Johns Hopkins Hospital. She now leads her own research laboratory focused on molecular characterization of pancreatobiliary neoplasms.
Acknowledgement of Support
I am honored to receive the AACR-Bristol Myers Squibb Midcareer Female Investigator Grant. I greatly appreciate this support at this critical stage in my career, which will enable our group to perform exciting new studies integrating cancer genomics, tumor immunology, and novel in vitro models of pancreatic neoplasia.
Radiation therapy (RT) has well known immune suppressive effects, including stimulating the expression of cytokines and chemokines that promote the migration of immune suppressive cell subsets into the tumor microenvironment (TME). Experiments in this project have been designed to test the hypotheses that 1) radiation promotes myeloid cell accumulation in the cervical TME via the CXCR2/ELR+ chemokine axis which limits anti-tumor immunity, and 2) selective targeting of CXCR2 will improve the efficacy of RT and RT combined with immune checkpoint blockade (RT + ICB). RT-associated changes in tumor associated macrophages (TAMs), neutrophils (TANs) and T cell subpopulations are set to be tracked using single cell RNA sequencing (sc-RNA) and mass cytometry (CyTOF) of human cervical tumor specimens collected before and during treatment. Selective targeting of myeloid cell infiltration with CXCR2 inhibition is set to be tested as a means to improve the response to RT and RT + ICB in a mouse model of HPV-associated cancer.
Dr. Schwarz earned her MD and PhD degrees in the Medical Scientist Training Program at Washington University School of Medicine in St. Louis (WUSM). She was a Holman Research Pathway resident in radiation oncology at WUSM. She currently serves as the cancer biology division chief within the Department of Radiation Oncology at WUSM. Her current research interests include radiation resistance, functional imaging, metabolism, and genomics in cervical cancer.
Acknowledgement of Support
I am honored to receive the AACR-Bristol-Myers Squibb Midcareer Female Investigator Grant. My lab studies radiation responses using human tumor specimens and mouse models of HPV-associated cancers. This funding will allow my lab to grow in a promising new direction. We will determine how radiation influences the immune-suppressive tumor microenvironment.