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.
Published article by Dr. Jaime Schneider in Nature Cancer Review, ‘ALK-Positive Lung Cancer: A Moving Target’
Jaime Schneider, M.D., Ph.D.:
Dr. Schneider began her scientific training as an undergraduate at Northwestern University in Evanston, IL where she earned her degree in Biology with a concentration in Biochemistry. She attended medical school at the Albert Einstein College of Medicine as part of the Einstein Medical Scientist Training Program (MSTP), one of the nation’s oldest physician-scientist training programs. There, she earned her M.D. and Ph.D. degrees and developed expertise in cellular and molecular biology. For her thesis work, she studied fundamental mechanisms of autophagy in the laboratory of Dr. Ana Maria Cuervo where she made significant contributions to the fields of autophagy, metabolism, and aging. Dr. Schneider received numerous accolades during her M.D./Ph.D. training including the Julius Marmur Research Award, Maurice Greenhill Memorial Award, Dean’s Recognition Award, and was awarded an individual NIH NRSA F30 fellowship to support work.
After completing medical school, Dr. Schneider trained as an Internal Medicine resident at the Massachusetts General Hospital (MGH) in Boston, MA, and became a leader in the MGH Stanbury Physician-Scientist program. Dr. Schneider matriculated into the Hematology/Oncology fellowship program at Harvard in 2018 where she trained as a medical oncologist at the MGH Cancer Center and the Dana-Farber Cancer Institute. She joined the laboratory of Dr. Marcia Haigis at Harvard Medical School for her post-doctoral work where she is investigating mechanisms of cancer resistance through metabolic reprogramming. She is the recipient of research awards including the MGH Translational Science Research Award, EGFR Resisters Top Breakout Award, and the Targeted Therapy of Lung Cancer Education Award. She is also committed to educating the next generation of physician-scientists as she teaches at Harvard Medical School and is the proud recipient of the 2019 Partners Graduate Medical Education Teaching Award. She is thrilled to win the A Breath of Hope 2022 Peg’s Fight for Life Award to continue her work on overcoming therapeutic resistance in oncogene-driven lung cancer. Her winning project is called: Metabolic Reprogramming in Oncogene-Driven Lung Cancer.
Dr. Schneider’s research focuses on non-small cell lung cancer (NSCLC), with a specific interest in cancers that harbor actionable oncogenic driver alterations. Using clinical samples and patient-derived models, she is using integrative metabolomics approaches to identify resistance mechanisms in oncogene-driven lung cancer. She is investigating whether specific onco-genotypes in lung cancer confer metabolic vulnerabilities and how metabolic reprogramming underlies resistance to targeted therapies. As a physician-scientist, Dr. Schneider is passionate about treating patients with lung cancer and is committed to developing novel therapeutic approaches using innovative scientific tools.
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.