I am an Assistant Professor of Molecular Medicine at Lerner College of Medicine of Case Western Reserve University (CWRU) and an Assistant Staff in the Genomic Medicine Institute of Cleveland Clinic. My academic journey has been marked by an unwavering pursuit of understanding and combatting cancer through rigorous training and groundbreaking research. Throughout my undergraduate and graduate studies, I received extensive training in both basic and translational aspects of cancer research, culminating in publication of six papers, including four first-author articles.
Building on this foundation, my postdoctoral studies provided me with specialized training in human breast cancer biology and the translation of basic science findings into clinical applications. Of particular significance to this proposal is a key finding from my postdoctoral research, where we identified approximately 25% sub-chromosomal copy number variations (CNVs) in the luminal progenitor cells from ostensibly normal breast tissues of individuals carrying germline BRCA2 mutations. This finding demonstrated that BRCA2 haploinsufficiency and associated DNA damage precede histologic abnormalities in vivo (Karaayvaz Yildirim et al, Science Advances 2020).
In 2021, I embarked on my independent academic career with a focus on elucidating the early events in breast cancer development to pioneer innovative breast cancer chemoprevention and treatment strategies. Leading a project on spatial transcriptomics of ostensibly normal breast tissues from BRCA1/2 germline mutation carriers, we uncovered spatially defined receptor-ligand interactions, mediating altered autocrine and paracrine signaling, elucidating critical aspects of mammary epithelial cell communication with the microenvironment. This study, published and featured on the cover of Molecular Cancer Research in February 2024, underscores the significance of understanding microenvironmental alterations in BRCA1/2 mutation carriers.
Following the establishment of my independent laboratory, I secured multiple seed grants to support my research endeavors. Notably, the Ohio Cancer Research awarded seed funding to investigate the potential of modulating mechano-signaling as a chemo-preventive measure in BRCA1/2 mutation carriers. Additionally, I benefit from in-kind support through the Cleveland Clinic - IBM Discovery Accelerator program, enabling the application of advanced machine learning algorithms to improve risk assessment for high-risk breast cancer patients using our omics and imaging datasets. Furthermore, the American Cancer Society awarded seed funding to explore the connection between BRCA2 haploinsufficiency and common fragile site instability in human mammary epithelial cells.
My proposal capitalizes on my specialized expertise in mammary epithelial cell biology and breast cancer biology in BRCA1/2 mutation carriers, within the outstanding scientific environment provided by Cleveland Clinic. Therefore, I strongly believe that receiving the NIH R01 award would be instrumental in achieving my long-term goal of advancing risk assessment and developing innovative breast cancer chemoprevention and treatment strategies for high-risk women.
The Karaayvaz Lab’s main research focus is to understand the early events in breast cancer development in high-risk patients. We employ state-of-the-art single cell and imaging approaches to dissect molecular heterogeneity in pre-malignant and malignant lesions of the breast. Our goal is to leverage the knowledge gained from these studies and develop innovative strategies for breast cancer chemoprevention and treatment.