Their Story
Dr. Kaufman’s Personal Statement
I am committed to a career focused on basic and translational research to improve the treatment of lung cancer. Specifically, I have applied integrated multi-omics analyses and various experimental approaches to characterize gene expression profiles, signaling pathways, and drug sensitivity patterns exhibited by lung adenocarcinomas that have lost the LKB1 tumor suppressor. This gene, a serine-threonine kinase also known as STK11, is lost in approximately 30% of lung adenocarcinomas. And this same gene has recently been shown to confer clinical resistance to immunotherapy.
My current work applies high throughput functional genomics approaches to model systems of LKB1 loss with the goal of
1) identifying novel clinical targets for LKB1 deficient lung cancer, and
2) discover mechanisms of resistance to immune checkpoint inhibition in this subset of tumors.
Grants Awarded
2021 LCFA/IASLC/BMS Young Investigator
About the LCFA-Funded Research
Dr. Jacob Kaufman’s LCFA Funded Project
Evaluating synergy between LKB1 and ATM loss in dictating immune response and differentiation state in NSCLC. Lung cancer is the leading cause of cancer death in the United States. Historically, advanced metastatic lung cancer had a 5% rate of survival at five years but this figure has been steadily increasing over the past ten years as new treatments have become available. Much of the improvement comes from advances in the field of ‘Immuno-Oncology‘ – novel treatments that activate the immune system to attack and control cancer. However, not all cancers respond well to these treatments, and multiple studies have shown that cancers with mutations in the LKB1 gene are inherently resistant to immunotherapy.
We have identified a specific subset of tumors with LKB1 loss that exhibit especially low levels of immune activation. These tumors exhibit many unusual molecular features that suggest that their biology is quite different from other tumors. In particular, they express high levels of genes associated with neuroendocrine differentiation and also frequently have inactivating mutations of a second gene “ATM” occurring in conjunction with LKB1.
Our analysis suggests that pathways regulating tumor differentiation and neuroendocrine features are likely to be linked to mechanisms of immune resistance and that LKB1 and ATM affect these processes, through unclear mechanisms. The goal of the work proposed is to gain understanding of these mechanisms, in hopes that this may allow the future development of novel treatment approaches to improve outcomes in these patients.
