Meet the Researchers

Jacob Kaufman, Md, PhD

Medical Oncology

Class of 2021

Understanding how the specific genetic background of each cancer affects their behaviors in patients

2022 Research Update

Unlocking the Secrets of STK11 Mutations in Lung Cancer

Dr. Kaufman’s passion lies in studying STK11 gene mutations, which are found in a subset of lung cancer patients. These mutations result in unique biology that sets these patients apart from others with lung cancer.

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.

Complete List of Published Works