2024-2026 Julie Swedberg YOLO Research Award Recipient
Principal Investigator: Jessica Konen, PhD, Winship Cancer Institute of Emory University, Department of Hematology and Medical Oncology
Project title: miR-29 as a master regulator of anti-tumor immunity
Jessica Konen, PhD, has dedicated her scientific career to researching mechanisms of tumor growth, metastasis, drug resistance, and immune evasion in non-small cell lung cancer (NSCLC). Dr. Konen began this work in graduate school at Emory University in Atlanta, Georgia, in the lab of Dr. Adam Marcus, where she studied the dynamic interactions between phenotypically distinct subpopulations within a collectively invading tumor pack. This work created significant contributions to the field of tumor invasion and metastasis, including revealing survival dependencies of the highly invasive leader cells that can be targeted as an anti-metastatic agent for the control of NSCLC.
After receiving her PhD, Dr. Konen completed her post-doctoral fellowship at The University of Texas MD Anderson Cancer Center in Houston, Texas. Here, she began her training in tumor immunology and immunotherapy, with a focus on KRAS-driven lung cancers. Her work in the laboratory of Dr. Don Gibbons led to several discoveries of novel tumor-driven resistance mechanisms to immune checkpoint inhibitors, revealing potential combination treatment strategies with small molecule inhibitors to combat immune checkpoint inhibitor resistance. During her pre-doctoral and post-doctoral training, Dr. Konen received numerous awards for her poster and oral research presentations and training fellowship awards through the NIH and the University of Texas Lung Cancer SPORE.
Currently, Dr. Konen is an instructor in the Department of Hematology and Medical Oncology at the Winship Cancer Institute of Emory University. Her research aims to continue to reveal targetable immune checkpoint resistance mechanisms in NSCLC, combining her backgrounds in studying dynamic, tumor-centric growth and metastasis mechanisms with a microenvironmental perspective of the extracellular matrix and anti-tumor immune response. Through this work, Dr. Konen hopes to reveal the vast heterogeneity of mechanisms that lung tumors utilize to escape immune detection and elimination in a spatiotemporal manner. She has received several accolades early in her career, including a Career Enhancement Proposal Award through the Emory University Lung Cancer SPORE and an American Cancer Society-Winship Internal Review Grant award.
Dr. Konen is excited to have received the ABOH Julie Swedberg YOLO research award to expand her research. She believes it will not only provide the necessary support for her research aspirations but also for the next steps of her career development. The proposed studies will generate the foundational data for the high-risk/high-reward next steps that Dr. Konen aims to take. The award will also help support the growth of several key collaborations with scientists at Emory University and other institutions.
About the project
Title: miR-29 as a master regulator of anti-tumor immunity: Dr. Konen’s project aims to define a vast transcriptional network that is dysregulated following loss of the micro-RNA (miR)-29 in tumors with resistance to immune checkpoint therapy. Specifically, the project aims to discover the tumor cell-intrinsic and extrinsic effects of miR-29 loss, including a focus on the cellular and non-cellular components of the tumor microenvironment, and to determine the efficacy of targeting this pathway to reinvigorate anti-tumor immunity and response to immune checkpoint inhibitor treatment. These studies will reveal previously unexplored biology of the miR-29 family with the goal of generating rational drug combinations for the treatment of lung cancer.
PROGRESS REPORTS
July 2025 Progress Report
During the second reporting period, we have continued to probe the micro-RNA miR-29 in lung cancer, with a focus on its role in modulating the functional ability of immune cells to penetrate and eliminate the tumor. Our recent data provides evidence that genetically re-expressing miR-29 within murine lung cancer models was sufficient to improve response to PD-1 blockade. Furthermore, we found that the combination of miR-29 expression plus anti-PD-1 significantly re-wired the tumor immune microenvironment towards a pro-inflammatory signature. These tumors had a significant influx of cytotoxic CD8+ T cells and a concurrent downregulation of suppressive myeloid cells known as monocytes. Supporting data was obtained in a dataset of lung adenocarcinoma patients that we delineated into miR-29 high and low groups. This analysis revealed the miR-29 high tumors also had increased CD8 expression and a reduction in the monocyte marker CD14. To add to these findings, we also generated cells with loss of miR-29 and found that miR-29 loss was capable of drastically altering immune cell phenotypes, specifically the CD8+ T cell compartment. Currently, we are testing whether forced miR-29 loss in turn drives resistance to anti-PD-1 immunotherapy. Upcoming studies will also aim to broadly assay gene expression signatures in miR-29 high and miR-29 low tumors, the goal of which is to create and determine the validity of a miR-29-dependent gene set as a biomarker of response to immunotherapy in patients. Lastly, we will continue to probe the utility of a pharmacological approach to introduce a miR-29 mimic in conjunction with anti-PD-1 to promote tumor rejection in both mouse and human models of lung cancer.
January 2026 Progress Report
During this reporting period, we examined the mechanistic effects of miR-29 on the functional ability of immune cells to invade the tumor and to transition to anti-tumor effector cell types, and how miR-29 loss impacts immunotherapy treatment response. Using a CRISPR-Cas9 approach, we depleted miR-29a from tumor cells and found that knockout of miR-29 expression was sufficient to cause anti-PD-1 therapy resistance, providing additional pre-clinical evidence that altering miR-29 expression has a valuable role in regulating anti-tumor immunity. Furthermore, re-expression of miR-29 in conjunction with anti-PD-1 therapy significantly re-wired the tumor immune microenvironment towards a pro-inflammatory (anti-tumor) signature. These tumors had a significant influx of cytotoxic and proliferative CD8+ T cells and a concurrent upregulation of pro-inflammatory macrophages, which produce and secrete an immunoattractant molecule, CXCL9. Our data revealed several soluble factors modulated by miR-29 which may impact differentiation of these pro-inflammatory macrophages, including LPA, CD93, and CD105. Based on these data, we are currently building upon the mechanism by which miR-29 directly and indirectly influences both CD8 T cell and macrophage differentiation. Upcoming studies will also aim to broadly assay gene expression signatures in miR-29 high and miR-29 low tumors, the goal of which is to create a miR-29-dependent gene signature to use as a biomarker of response to immunotherapy in patients. Lastly, we aim to develop a new miR-29 mimic therapy with increased stability and tumor-targeting potential to probe a potential clinical path for targeting this pathway in combination with immune checkpoint inhibition for the management of lung cancer.