AACR-Pfizer Breast Cancer Fellowship
The AACR-Pfizer Breast Cancer Research Fellowships represent a joint effort to encourage and support postdoctoral or clinical research fellows to conduct breast cancer research and to establish a successful career path in the field. Funded research can be basic, translational, clinical, or epidemiological in nature.
A connection between lipid metabolism and estrogen receptor negative breast cancer development has been demonstrated. Exposing non-transformed breast epithelial cells to lipid increases metabolic flux and histone methylation and alters gene expression. Dr. Bustamante’s preliminary data showed lipid-induced production of S-adenosyl methionine (SAM), the oncometabolite 2-Hydroxyglutarate (2-HG), and antioxidant defenses. She hypothesizes that lipid metabolism enables the survival of specific luminal progenitor cells and simultaneously increases SAM and 2-HG, and consequently, histone methylation. This leads to epigenetic-fostered plasticity, resulting in an inappropriate neural/neural stem differentiation associated with malignant transformation. She is set to pursue these provocative results at the intersection of neurobiology and breast cancer biology.
Dr. Bustamante Eduardo obtained her undergraduate degree in biology from the Universidad Mayor de San Simon in Cochabamba, Bolivia, and a master’s degree in biology (option Genetics, Development and Evolution) from the University of Geneva, Switzerland. She received her doctorate in biochemistry and molecular biology from the University of Bern, Switzerland where she studied breast cancer heterogeneity, with a special focus on the progesterone receptor. She is currently a postdoctoral researcher at Northwestern University. Her research focus is on breast cancer prevention, specifically studying the connection between lipid metabolism, epigenomic reprogramming and malignant transformation.
Acknowledgement of Support
“I am honored to be awarded the AACR-Pfizer Breast Cancer Research Fellowship to continue working in breast cancer prevention. This opportunity will allow me to contribute to the understanding of local breast biology that promotes the development of estrogen receptor negative breast cancer, which is critical for developing biomarkers and novel preventive strategies.”
Making major impacts on the incidence and lethality of BRCA1/2 breast cancer requires increased knowledge of the target cells of pathological transformation . Luminal progenitors (LPs), the suspected cancer cell of origin of BRCA1/2 breast cancer, are found to display frequent polyclonal chromosomal damage. This damage may endow them with the capacity for context-dependent multi-lineage differentiation, and may allow them to exhibit a degree of cellular plasticity, resulting in the development of either BRCA1 basal type or BRCA2 luminal type breast cancer . Dr. Ren aims to 1) discover markers defining LPs that may propel the development of new tissue-based predictors of breast cancer risk; 2) identify key regulators that may endow damaged LPs the capacity to differentiate into distinct breast cancer types; and 3) explore therapeutic vulnerabilities that could be exploited to eliminate these cells, as a possible cancer prevention strategy.
Dr. Ren completed his doctorate at the Albert Einstein College of Medicine, New York, in breast cancer and pathology. He is currently a postdoctoral fellow at Massachusetts General Hospital and Harvard Medical School, where he is employing surgical specimens from BRCA1/2 mutation carriers to dissect early pathogenesis of hereditary breast cancer for risk prediction and prevention.
Acknowledgement of Support
“I am honored and grateful to have been selected to receive the AACR-Pfizer Breast Cancer Research Fellowship. This invaluable support will provide me with an opportunity to better understand the process of hereditary breast cancer development and fulfill this unmet need in breast cancer field, and it will absolutely be a highlight of my academic career.”
HER2 positivity accounts for 15-20% of breast cancer and has traditionally been associated with poor prognosis. While HER2-targeted therapies significantly improve clinical outcomes, many patients develop resistance and progress to metastatic disease and death. Dr. Xiao aims to delineate the genomic evolution and transcriptional reprogramming of the tumor cells and the tumor microenvironment during HER2-targeted therapy resistance using high throughput single-cell DNA and RNA sequencing methods. Completion of the proposed proposal will greatly improve our fundamental understanding of the resistance to HER2targeted therapy and is expected to identify new therapeutic targets in the tumor, stromal and immune cells that can be exploited to overcome resistant disease in HER2-positive breast cancer patients and predict therapeutic response.
Dr. Xiao obtained her PhD at UT MD Anderson UT Health Graduate School of Biomedical Sciences, where she studied deubiquitinating enzymes that promote breast cancer progression and migration via regulating protein stability. She is currently a Postdoctoral Fellow in the Department of Genetics at MD Anderson Cancer Center. Her research mainly focuses on delineating the role of clonal evolution and intratumor heterogeneity in therapy resistance in human breast cancer using single-cell genomics.
Acknowledgment of Support
It is my great honor and pleasure to be a recipient of the AACR-Pfizer Breast Cancer Research Fellowship. This fellowship will not only support the proposed research work but also provide me with an invaluable opportunity to pursue my career objective toward becoming an independent cancer research investigator.
A feared complication of metastatic breast cancer is the development of brain metastases (BM) due to the substantial morbidity and limitations in current treatments. While precision medicine approaches for BM have recently demonstrated promising responses, many patients are not able to benefit from this treatment paradigm as molecular analysis of BM tissue is not usually feasible. To answer this question, Dr. Kim will apply genomic profiling and deep learning methods to a rich dataset comprised of breast cancer BM tissues, patient-matched brain MRIs, and cell-free DNA samples in order to develop techniques that reveal therapeutic targets within a patient’s BM. His hope is that these findings will shift current paradigms – for example, a lumbar puncture and MRI, instead of tissue from a neurosurgical resection, may be opportunities to non-invasively identify oncogenic drivers for a BM and longitudinally monitor breast cancer evolution.
Dr. Kim attended medical school at the Medical College of Georgia. He completed neurology residency training at Washington University in St. Louis and is a neuro-oncology fellow at the Dana-Farber/Partners Cancer Care Program. He is an Instructor at the Massachusetts General Hospital Cancer Center, where he sees patients at the Pappas Center of Neuro-Oncology. Dr. Kim is also a post-doctoral fellow at the MGH Brain Tumor Center and the MGH Martinos Center, where he uses Omics-based techniques and medical imaging to define and target genomic and metabolic pathways for brain metastases.
Acknowledgment of Support
I am deeply humbled and honored to be a recipient of the AACR-Pfizer Breast Cancer Research Fellowship. As an oncologist-in-training, I am dedicated to a career leading a translational group that facilitates precision medicine for patients with brain metastases. This award provides critical support for my transition to independence.