Claudia Adams Barr Program
Program Advancements
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Blood Cancers
Finding New Therapeutic Targets for Blood Cancers
James Griffin, MD, uncovered evidence that a protein, BRD7, plays a critical role in the development of blood cancers, including acute myeloid leukemia (AML), an aggressive leukemia. His team is targeting BRD7 with small molecules as prototypes for leukemia therapies and investigating how BRD7 promotes leukemia cell survival during blood development.
Brain Cancers
New Treatment Opportunities
Rosalind Segal, MD, PhD, parlayed her funding into the discovery that a genetic pathway called “Notch” is consistently damaged in brain tumors. Drugs already existed for other diseases to target Notch, and clinical trials are now exploring opportunities to use these drugs to improve survival for patients with brain cancer.
Breast Cancers
New Function for BRCA1
Elodie Hatchi’s, PhD, research shed new light on one way that the BRCA1 gene functions at a molecular level. Dr. Hatchi’s unprecedented work is the first to identify and outline the relationship between BRCA1 and unusual DNA structures, and the role this interaction may play in forming breast cancer cells.
Cancer Biology
Unlocking the Mysteries of Genomic Rearrangements
Cheng-Zong Zhang, PhD, is exploring whether breakage-fusion-bridge (BFB)-induced genetic rearrangements are more likely to occur at DNA sites undergoing transcription, how they affect transcription, and the impact this has on cellular behaviors. This may lead to clues about cancer development, achieving better prevention strategies and combatting drug-resistant tumors.
Cancer Genetics
Uncovering New Links Between Metabolism and Cancer
Edward Chouchani, PhD, has uncovered that accumulated lactate interacts with and modifies the activities of specific proteins influencing cancer cell growth and proliferation. He is working with colleagues to uncover the molecular basis for lactate’s protein interactions and to identify other key proteins that lactate targets to influence cancer cell activities.
Immunotherapies
New Ways to Activate the Immune System
Glenn Dranoff, MD, discovered complex regulatory pathways in the immune system that cancers exploit to escape destruction. Reversal of these effects can lead to the development of vaccines against cancer, like Provenge for prostate cancer, and has enabled development of immune-activating drugs such as ipilimumab, which is approved by the FDA for metastatic melanoma.
Lung Cancer
Targeting KRAS in Lung and Colorectal Tumors
Fay Nicolson, PhD, is developing non-invasive strategies for detecting and treating KRAS G12C-driven lung tumors using two radioactive agents. The first is used during a PET scan to visualize tumors with the mutation; the second delivers toxic radiation directly to mutant tumor cells while leaving normal cells unharmed.
Ovarian Cancer
Leveraging the Immune System to Fight Ovarian Cancer
Han Dong, PhD, identified a cellular communication network helping memory-like natural killer cells grow and survive longer. She is testing if manipulating this network encourages these cells to attack and eliminate ovarian tumors and whether cancer-fighting activity can be boosted through small molecules helping to retain their anti-cancer properties in the microenvironment.
Pancreatic Cancer
Modeling Pancreatic Cancers to Fuel Discovery
Srivatsan Raghavan, MD, PhD, is generating mouse models for basal and classical pancreatic cancers to identify drugs that work selectively against each subtype. He is also looking for molecular signals in tumor environments that cause one type to switch to the other, which could lead to new therapeutic targets for this hard-to-treat disease.
Pediatric Cancers
Finding New Weaknesses in Pediatric Brain Tumors
Volker Hovestadt, PhD, studies pediatric brain tumors forming during early-stage brain development before a child is born. He is using stem cells to generate “mini-brains” and manipulating their molecular properties to induce tumor formation, with the goal of learning how embryonic brain tumors develop and identifying vulnerabilities within them to target.
Precision Medicine
Determining When to Use Chemotherapy
Anthony Letai, MD, PhD, developed a powerful test determining whether a patient's cancer cells will be destroyed by chemotherapy, which enables physicians to select the most appropriate treatment. Dr. Letai is now confirming the efficacy of this test, with the goal of making it available for a range of different cancer types.
Prevention
Developing a Cancer Prevention Drug
Bruce Spiegelman, PhD, is using mass spectrometry to test metformin—a type 2 diabetes drug that has shown cancer prevention potential—against thousands of proteins to identify which will bind to the drug. Should a target protein be validated, he aims to partner with chemists to develop a more potent form of metformin.