C. Ryan Miller, MD, PhD (Damon Runyon Clinical Investigator ’09-’12) of the UNC Lineberger Comprehensive Cancer Center, Chapel Hill, and colleagues, reported two studies on the genetics underlying brain tumors. The first study showed that mutations in MAPK and PI3K affect how cancer starts in glial cells, brain cells that provide support and insulation for neurons. These mutations triggered tumor initiation and produced increasingly dense low-grade gliomas that quickly progressed to aggressive and often deadly glioblastoma (GBM).

Election to the National Academy of Sciences is one of the highest honors that can be earned by a U.S. scientist.  In recognition of their distinguished and continuing achievements in biomedical research, members of the Damon Runyon community of scientists were inducted this month:  

Ardem Patapoutian, PhD (Damon Runyon Scholar ’03-‘05, Fellow ’96-‘99), Scripps Research Institute, La Jolla

Guillermina Lozano, PhD (Former Fellowship Award Committee Member), M.D. Anderson Cancer Center, Houston

Feng Zhang, PhD (Damon Runyon-Rachleff Innovator ’12-’14) and colleagues at the Broad Institute, Cambridge, have developed a new CRISPR-based genetic diagnostic tool that may make it faster, less expensive, and easier to diagnose acute and chronic diseases like Zika, Ebola, cancer, and other hereditary disorders. The new tool dubbed SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) can detect extremely low concentrations of Zika virus and cancer DNA in blood, urine, and saliva samples. Previous CRISPR systems target DNA, but this system targets and degrades RNA.

Jedd D. Wolchok, MD, PhD (Damon Runyon-Lilly Clinical Investigator ‘03-‘08) at Memorial Sloan Kettering Cancer Center, New York, and colleagues, reported that matching the size of a tumor to the body's immune response could help doctors tailor immunotherapy treatments for melanoma patients whose disease has spread.

David M. Livingston, MD (Damon Runyon Board Member), of Dana-Farber Cancer Institute, Boston, has been named the 20th recipient of the Pezcoller Foundation-AACR International Award for Cancer Research. Dr. Livingston is honored for his fundamental contributions to the field of basic cancer research. His work has been pivotal to the understanding of retinoblastoma pathway of cell cycle control as well as the transcriptional co-activation function of the key regulatory proteins, p300 and CBP.

At the junction of growth and starvation stands a signaling protein called mechanistic Target of Rapamycin Complex 1 (mTORC1). Inside the cell, mTORC1 regulates metabolism, growth, protein and organelle recycling (autophagy), proliferation, and survival. When something goes wrong in the pathway, various diseases such as cancer, obesity, and type 2 diabetes, can develop. An outstanding challenge is to understand how mTORC1 becomes activated in response to a wide variety of stimuli including nutrients, growth factors, and stressors, in normal and cancer states.

Anjana Rao, PhD (Damon Runyon Fellow ’79), and James Scott-Browne, PhD (Damon Runyon Fellow ’11-’13), at the La Jolla Institute for Allergy and Immunology, La Jolla, and colleagues, are focusing on a key issue of how tumor-fighting T cells can lose their effectiveness or become “exhausted.”  The researchers identified two proteins, NFAT and Nr4a, that can bind to the DNA of T cells and shut down their tumor-fighting activity.  Next steps will be to determine if these processes can be interfered with or reversed in order to re-motivate immune cells to eradicate a pati

Don X. Nguyen, PhD (Damon Runyon Fellow ’05-’08), of Yale Cancer Center, New Haven, and colleagues, reported new findings that explain the propensity of latent lung adenocarcinoma (LUAD) to relapse. They showed that differential expression of extracellular matrix (ECM) molecules and their interacting proteins contributes to risk of relapse in distinct LUAD subtypes. One protein called hyaluronan receptor HMMR, when overexpressed, was associated with inflammation and poor prognosis.

Christine Iok In Chio, PhD (Damon Runyon Shirley Stein Fellow ’13-’17), in the laboratory of her sponsor David Tuveson, MD, PhD, and colleagues at Cold Spring Harbor Laboratory, Cold Spring Harbor, created a new 3D model of pancreatic cancer, which allowed them to identify two distinct stroma cell populations called cancer-associated fibroblasts  (CAF’s), that work together with cancer cells to protect and help the tumor grow.

Gregory L. Beatty, MD, PhD (Damon Runyon-Nadia’s Gift Foundation Innovator ’12-’15) and colleagues at the Abramson Cancer Center at University of Pennsylvania, Philadelphia, reported high levels of inflammatory compounds in mice with pancreatic tumors. These included CCL2, a signaling molecule that promotes recruitment of inflammatory white blood cells by tumors. This likely contributes to the protective tumor microenvironment that makes most pancreatic tumors resistant to treatment. CCL2 levels increased further after the mice received radiotherapy.