2022 A Breath of Hope Research Award Recipient

Jaime Schneider, M.D., Ph.D. of Massachusetts General Hospital

A Breath of Hope is pleased to announce our 2022 Peg’s Fight For Life Research Award to Jaime Schneider, M.D., Ph.D. of the Massachusetts General Hospital, the largest teaching hospital of Harvard Medical School, for her project entitled: Metabolic Reprogramming in Oncogene-Driven Lung Cancer. We are so proud of the work we funded which has now been published!

2023: Congratulations to Dr. Jaime Schneider for her published article in Nature Cancer Review, ‘ALK-Positive Lung Cancer: A Moving Target’

2025: Congratulations to Dr. Jaime Schneider for her published article in CELL: GUK1 activation is a metabolic liability in lung cancer – ScienceDirect

Jaime Schneider, M.D., Ph.D.:

Dr. Schneider

Dr. Jaime L. Schneider, MD, PhD is a thoracic medical oncologist and physician–scientist at Dana-Farber Cancer Institute (DFCI) and Harvard Medical School. She cares for patients with lung cancer and leads an independent laboratory in the Division of Molecular and Cellular Oncology focused on cancer metabolism and therapeutic resistance.
 
Dr. Schneider earned her B.A. in Biology from Northwestern University, followed by her M.D. and Ph.D. in Molecular and Cell Biology at Albert Einstein College of Medicine. She completed internal medicine residency at Massachusetts General Hospital through the Stanbury Physician-Scientist Pathway, medical oncology fellowship at the Dana-Farber/Harvard Cancer Center (DF/HCC), and postdoctoral training in the Department of Cell Biology at Harvard Medical School.
 
Dr. Schneider practices in the Lowe Center for Thoracic Oncology at DFCI with a focus on oncogene-driven non–small cell lung cancers (NSCLCs). Her laboratory uses patient-derived models and translational approaches to define how oncogenotypes shape metabolic dependencies and how metabolic rewiring drives resistance to targeted therapies. She has published in Cell, Nature Cancer, Cell Metabolism, Nature Communications, NPJ Precision Oncology, The Oncologist, Aging Cell, and JTO Clinical and Research Reports. Her research is supported by the American Cancer Society, Lung Cancer Research Foundation, A Breath of Hope Lung Foundation, Gilead Solid Tumor Oncology Program, the ROS1ders Foundation, DF/HCC K12 Career Development Award, and the Harvard Shore Faculty Development Program.
 
Dr. Schneider’s honors include the American Society for Clinical Investigation (ASCI) Emerging-Generation Physician-Scientist Award, IASLC Targeted Therapies in Lung Cancer Education Awards, AACR Scholar-in-Training Award, William Guy Forbeck Scholar, “40 Under 40 in Cancer” Award, and the ROS1 Cancer Innovation Award. She serves as Associate Editor-in-Chief of Translational Cancer Research, on the editorial board of Translational Lung Cancer Research, and on the IASLC Basic and Translational Science Committee and ASCI Physician-Scientist Development Committee.
 
Through her dual roles in patient care and laboratory research, Dr. Schneider is committed to advancing scientific discoveries into new therapies to improve survival and quality of life for patients with cancer.
 

About the Project:

Dr. Schneider’s project aims to identify novel strategies to overcome resistance to targeted therapies in oncogene-drive lung cancer. Dr. Schneider’s work aims to (1) uncover unique metabolic dependencies conferred by distinct onco-genotypes, and (2) understand whether metabolic reprogramming drives resistance to targeted therapy. These studies will uncover previously unknown metabolic vulnerabilities that can pave the way for new therapeutic approaches for patients with lung cancer.

Metabolic Reprogramming in Oncogene-Driven Lung Cancer

Principal Investigator: Dr. Jaime Schneider, M.D., Ph.D.

June 2023 Progress Report:

During the reporting period, we have continued our studies to examine metabolic dependencies in oncogene-driven lung cancer. A phosphoproteomic screen identified several novel metabolic targets of oncogenic fusion kinase signaling. Using ALK+ non-small cell lung cancer as a framework, we validated several top candidates from the proteomic screen and confirmed that ALK signaling regulates various aspects of cellular metabolism through post-translational modification. We identified that beyond ALK, other oncogenic fusion kinases regulate metabolic enzymes through phosphorylation to modulate nucleotide synthesis. Excitingly, we also identified that certain metabolic targets of oncogenic signaling undergo differential regulation in drug-resistant patient-derived cell lines. Currently, we are expending the battery of resistant lines for metabolomics experiments and correlating whether nucleotide metabolite profiles align with post-translational modifications and regulation of these metabolic targets. Future work will focus on determining metabolic mediators of targeted therapy resistance.

December 2022 Progress Report:

During the reporting period, we have continued our studies to examine  metabolic dependencies in oncogene-driven lung cancer. Using ALK+ non-small cell lung cancer as a framework, we identified a distinct metabolic signature in ALK-driven lung tumors marked by altered handling of purine nucleotides across different model systems including patient-derived cell lines, orthotopic mouse model of ALK+ NSCLC, and in patient tumor specimens. We validated several hits from our phosphoproteomic screen that identified novel metabolic targets of oncogenic signaling that directly modulate cellular metabolism. We have focused the majority of our efforts on a top hit from our phosphoproteomic study that controls purine nucleotide biosynthesis. We confirmed direct interactions between oncogenic fusion proteins and metabolic enzymes and confirmed that phospho-mutant forms of metabolic enzymes slow tumor proliferation in culture and in vivo. We have developed an antibody with specificity against post-translationally modified metabolic targets and demonstrated that it is tumor-specific. Excitingly, we identified that certain metabolic targets of oncogenic signaling undergo differential regulation in drug-resistant patient-derived cell lines. Currently, we are expending the battery of resistant lines for metabolomics experiments and correlating whether nucleotide metabolite profiles align with post-translational modifications and regulation of these metabolic targets.

Dr. Schneider recently participated in an expert panel discussing the detection and treatment of ROS1+ NSCLC for healthcare professionals. Learn more HERE.