The Eichner lab studies transcriptional dependencies in cancer development, progression, and resistance mechanisms. We endeavor to elucidate in vivo transcriptional dependencies at the intersection of epigenetics, signaling, and metabolism to reveal and harness therapeutically targetable transcriptional vulnerabilities in cancer.
Project 1
LKB1 (STK11) is among the most frequently mutated genes in Non-Small Cell Lung Cancer (NSCLC), where it is inactivated in ~20% of cases. Leveraging immune-competent genetically engineered mouse models to answer key questions in vivo, our work has revealed key insights into the molecular mechanisms driving this disease. We have identified that transcription plays an important and previously underappreciated role in mediating LKB1 function. Future work continues utilizing mechanistic understanding to explore novel in vivo transcriptional dependencies and therapeutic liabilities of LKB1 mutant tumors.
Project 2:
We have identified critical roles of the druggable epigenetic regulator Histone Deacetylase 3 (HDAC3) in lung tumors. We found that HDAC3 directly represses a secretory gene expression program, and impacts the tumor immune microenvironment in vivo. Future work continues defining the molecular mechanisms mediating HDAC3’s contribution to tumorigenesis.
Project 3:
Our molecular studies have led us to discover a druggable mechanism of therapeutic resistance in lung cancer. Supported by the Robert H. Lurie Comprehensive Cancer Center and the American Cancer Society Mission Boost program, we are working toward clinical translation of these findings. We also continue to explore molecular mechanisms of therapeutic resistance.