The rise of single-cell RNA sequencing in recent years has transformed the study of gene expression, providing researchers with a detailed picture of how and when genes get turned “on” and “off” in individual cells within a given tissue. Analyzing cells’ RNA sequences, or transcriptomes, can reveal cell-to-cell variability, or in the case of cancer, mutations carried by small populations of tumor cells. Current single-cell sequencing methods, however, fail to capture the location of the cell within the tissue. Spatial transcriptomics techniques, on the other hand, define the spatial distribution of RNA molecules within a tissue sample, but lack single-cell resolution. To put this on a human scale, consider the different information you get about a neighborhood from a phone book versus a satellite image.

Damon Runyon has announced its newest cohort of Quantitative Biology Fellows, three exceptional early-career scientists who are applying the tools of computational science to generate and interpret cancer research data at extraordinary scale and resolution. Whether measuring cell-to-cell genetic variability within a tumor or developing algorithms that can predict if therapy will be effective, their projects extend the boundaries of what is possible in cancer research, allowing them to tackle fundamental biological and clinical questions.

For many patients with colon cancer, the advent of immune checkpoint inhibitors has substantially improved their treatment options. Immune checkpoint inhibitors (ICIs) work by removing the “brakes” from immune T cells, unleashing them on cancer cells. Unfortunately, however, ICIs do not work for everyone, and they can have life-threatening side effects for some patients. Given these factors, ICIs should only be used in patients who have the potential to benefit from them—the problem is, clinicians are often unable to predict who those patients will be.

CAR (chimeric antigen receptor) T cell therapy, in which a patient’s own immune cells are genetically engineered to target and kill cancer cells, has revolutionized the treatment of certain blood cancers. However, up to 60% of patients receiving CAR T therapy still experience relapse and up to 80% of patients experience serious side effects, including neuroinflammation—both of which present an obstacle to CAR T therapy’s widespread adoption.

Many blood cancers, including leukemia and multiple myeloma, arise when early blood-forming cells do not develop properly. Mistakes in cell differentiation—the process of maturing from a stem cell into a specialized cell type—can cause these abnormal blood cells to grow and divide uncontrollably. But exactly what goes wrong (and why) in the course of cell development is often difficult to determine after the tumor has already grown.

For the past 15 years, a group of researchers at the University of Illinois at Urbana-Champaign has been developing chemical building blocks for the synthesis of organic (carbon-based) small molecules. These building blocks, called MIDA boronates, snap together like puzzle pieces and can be assembled into a range of products, from manufacturing materials to food ingredients. The team even created a molecule-building machine to automate the process. As versatile as MIDA boronates are, however, they are much more stable in flat molecules than in 3D space. To advance in the world of chemical synthesis, scientists need Legos, not puzzle pieces.

New research indicates that hyaluronic acid (HA), a sugar-based compound naturally produced by the body and a popular ingredient in skincare products, also plays a role in fueling pancreatic cancer growth. Former Damon Runyon Fellow and Breakthrough Scientist Costas A. Lyssiotis, PhD, at the University of Michigan explains this finding in a recent paper published in eLife.

Translocation renal cell carcinoma (tRCC) is a rare but aggressive type of kidney cancer that disproportionately affects women and children. These cancers arise when part of a chromosome breaks off and fuses to a different chromosome, an event known as translocation. In tRCC, the fusion occurs between genes in the MiT/TFE family, which code for proteins called transcription factors that turn other genes on or off. Beyond this, however, the molecular basis of the disease is poorly understood. Due to this cancer’s rarity, doctors have an incomplete picture of its clinical features and no established standard of care. As a result, patients with tRCC are treated with therapies developed for other kidney cancers, with uneven success.

Barrett’s esophagus is a condition caused by chronic acid reflux, in which stomach acid repeatedly flows up into the esophagus, eventually affecting the cells at the juncture of the esophagus and the stomach. While not harmful in itself, Barrett’s esophagus can develop into esophageal cancer in a minority of cases. Patients are advised to get regular imaging of their esophagus to check for abnormal-looking (precancerous) cells, which can be treated if discovered on time. But until recently, scientists misunderstood exactly what kind of cells they were looking at.

For decades, a weakened immune system has been considered an unavoidable side effect of receiving radiation or chemotherapy. These treatments, while highly effective at killing cancer cells, also deplete the body’s store of blood stem cells and damage the area in the bone marrow where new ones are produced. Blood stem cells, also known as hematopoietic stem cells (HSCs), are critical for a functioning immune system because they give rise to all other blood cells, including white blood cells.