New Discoveries and Honors

Read about the latest discoveries by Damon Runyon scientists and honors received by scientists in the Damon Runyon scientific community.

September 26, 2022

Follicular lymphoma is a slow-growing cancer that occurs when the body produces abnormal B cells that form clumps, or “follicles,” in the lymph nodes. Like T cells, B cells are a type of white blood cell integral to the immune system. Unlike T cells, which attack the body’s own cells when they become infected or cancerous, B cells produce antibodies that target invading bacteria, viruses, and other pathogens.

September 15, 2022

As we know well by now, vaccines must be updated periodically because viruses constantly evolve new strains that may or may not bind to our existing antibodies. The influenza vaccine, for example, is updated every year; it seems likely that the SARS-CoV-2 vaccine will follow the same cadence. To develop and update these vaccines, researchers must test how panels of antibodies respond to panels of viruses. The number of possible antibody-virus combinations makes testing every interaction impractical, so even the most laborious studies have to settle for non-exhaustive data.

September 1, 2022

The proteins CDK4 and CDK6 are well-known regulators of the cell cycle, driving cells into the DNA replication phase that occurs before cell division. Since their discovery in the 1990s, scientists have understood that mutations in these regulatory proteins can lead to uncontrolled cell division, or cancer.  Thanks to persistent research efforts over the past thirty years, CDK4/6 inhibitors have been approved for the treatment of breast cancer, but given the disruptive power of these oncoproteins, it is likely that such inhibitors could be effective for other types of cancer as well. When it comes to targeted therapies, more specific means less toxic, so understanding which proteins to target in each cancer is a crucial first step.

August 22, 2022

The outermost layer of the human brain, known as the cerebral cortex, is responsible for our highest mental capacities—language, memory, emotion, decision-making, and much more. It contains an immense diversity of cells, between 14 and 16 billion neurons, organized in patterns complex enough to elude the farthest reaches of neuroscience.

August 19, 2022

As anyone who has undergone chemotherapy or radiation therapy knows, nausea is a frequent and distressing side effect and anti-nausea medications do not always work. Effective remedies for nausea are critical for cancer patients’ quality of life and ability to continue with treatment. But as with many types of pain, such remedies require a better understanding of the neural pathways that produce the sensation.

August 17, 2022

Head and neck squamous cell carcinoma, or HNSCC, is a cancer that develops in the mucous membranes of the mouth, nose, and throat, most often affecting men in their 50s and 60s. HNSCC is generally treated with surgery, followed by chemotherapy and/or radiation, but given the functional importance of the affected area, less severe treatment options could vastly improve patients’ quality of life. Additionally, the prognosis for patients with human papillomavirus (HPV)-positive head and neck cancer is much better than that of HPV-negative patients, highlighting the need for expanded treatment options.

July 29, 2022

Despite the best efforts of cancer researchers and clinicians, pancreatic cancer remains a highly lethal disease, with only 5% of patients surviving 5 years after their diagnosis. This is in part because pancreatic cancer cells have relatively few mutations, meaning fewer strange-looking proteins, or neoantigens, on their surface to attract the attention of cancer-killing immune T cells. This makes most pancreatic tumors “immune cold,” safe from detection by the body’s defense system.

July 14, 2022

Ras proteins, present in all mammalian cells, are molecular switches that control the processes of cell survival and proliferation. Unsurprisingly, mutations in any of the three RAS genes (KRAS, NRAS, or HRAS) can lead to uncontrolled cell growth, or cancer. Since these cancer drivers were first identified in the 1980s, it has been clear that different types of cancer are coupled with specific RAS mutants. For example, nearly 90% of pancreatic tumors display KRAS mutations, while NRAS mutations are more likely to appear in blood cancers. Why these associations exist, however, is not well understood.

July 13, 2022

Colorectal cancer is among the leading causes of cancer deaths worldwide, second only to lung cancer. As with many cancers, the primary cause of death in this type of cancer is metastasis, or when the cancer spreads from its original tissue to another organ in the body. In colorectal cancer, the liver is most common site of metastasis—more than half of all colorectal cancer patients will develop tumors in their liver during the course of their disease. Targeting the genes and pathways that promote liver metastasis may be key to developing better treatments for colorectal cancer, but until recently, these genetic mechanisms were not well defined.

July 11, 2022

Like living species, cancer cell populations undergo evolution. They accumulate mutations and become heterogeneous, and the mutations that increase chances of survival become more common. In this way, a single genetic alteration can evolve into a tumor and eventually spread throughout the body. Understanding the evolutionary path that tumors follow, from a single-cell mutation to metastatic cancer, is essential for designing effective clinical interventions. However, environmental factors and other variables can confound efforts to trace a cancer’s development from beginning to end.

July 8, 2022

Cancer treatment decision-making depends on an accurate understanding of a patient’s prognosis. Mistaking a cancer’s aggressiveness can lead to either under- or overtreatment, both of which carry increased risk of fatality. Current methods of prognostication, which usually rely on examining cancerous tissue via X-ray or microscope, involve subjective judgments and sometimes fail to predict disease course. With the rise of DNA sequencing technologies, clinicians are increasingly looking to patients’ genomes for clues about how their cancer will behave.

June 23, 2022

Last fall, we published the story of Damon Runyon Clinical Investigator Jennifer M. Kalish, MD, PhD, a pediatric geneticist at the Children’s Hospital of Philadelphia who has dedicated her career to the study of Beckwith-Wiedemann Syndrome (BWS), a rare genetic condition that causes overgrowth in certain parts of the body and predisposes children to cancers of the kidney and liver. As Founding Director of the hospital’s Beckwith-Wiedemann Syndrome Clinic, Dr. Kalish established the country’s first and only active BWS patient registry and biorepository storing blood and tissue samples necessary for research. In December 2020, her lab unveiled the first human cell-based model of the syndrome, developed using cells from patients in the registry.

June 13, 2022

Damon Runyon alumni Ash Alizadeh, MD, PhD, and David Kurtz, MD, PhD, and others have shown that cancer can be detected via blood sample by measuring circulating tumor DNA (ctDNA). This approach, however, requires high concentrations of tumor DNA in the bloodstream and provides low resolution—in other words, it can detect cancer but cannot identify a specific cancer subtype.

June 9, 2022

Cells absorb hormones, proteins, and other molecules from their environment through a process called endocytosis. In this process, the molecule being absorbed—the “cargo”—binds to a receptor on the surface of the cell membrane, recruiting a protein called clathrin to the inside of the cell membrane. The membrane then pinches inward to form a clathrin-coated vesicle with the cargo protected inside. Endocytosis is mediated by a protein complex called AP2, which links the cargo-bound receptors to the clathrin coat (see below). The functionality of AP2 depends on its shape. When “closed,” it can only bind to the cell membrane; when “open,” it can bind to cargo-bound receptors and clathrin proteins. But how exactly it makes this conformational change from “closed” to “open” has long been unclear. 

June 7, 2022

Founded in 1780, the American Academy of Arts and Sciences is both an honorary society that recognizes and celebrates the excellence of its members and an independent research center that convenes leaders from across disciplines to address significant challenges facing the world. This year, four Damon Runyon scientists were among the 261 exceptional individuals elected to the Academy.

May 16, 2022

Patients with ovarian cancer have a 92% five-year survival rate if they are diagnosed at stage I. But a lack of effective screening methods and absence of symptoms in its early stages makes ovarian cancer particularly difficult to catch before it spreads. Patients and clinicians need a kind of internal alarm system, a device that can detect and communicate the presence of cancer cells in the body before they have a chance to inflict damage.

May 10, 2022

Messenger RNA (mRNA) vaccines have been shown to elicit immunity against a number of infectious diseases—including, notably, COVID-19—as well as several types of cancer. Unlike traditional vaccines, which introduce a small amount of the pathogen into the body, mRNA vaccines provide the body with instructions for how to make a specific protein found on the surface of a virus or cancer cell. Once the vaccine is delivered, molecular machines called ribosomes bind to the mRNA, “read” its instructions, and build the protein. This, in turn, prompts the immune system to produce the corresponding antibodies, so that it is ready when it encounters the real virus or cancer cell. Importantly, the mRNA molecules that contain these protein-making instructions are broken down by the cell after they have delivered their “message.”

April 25, 2022

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.

April 13, 2022

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.

April 8, 2022

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.

March 16, 2022

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.

March 4, 2022

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.

March 1, 2022

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.

February 18, 2022

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.

February 15, 2022

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.

February 10, 2022

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.

February 7, 2022

An effective immune system response requires coordination among many types of immune cells, including CD4+ (helper) T cells, CD8+ (cytotoxic) T cells, and B cells. Helper T cells recognize antigens—identifying molecules on the surface of a pathogen—and release warning signals. These signals activate cytotoxic T cells, which kill the infected or cancerous cells, and B cells, which produce antibodies to attack the pathogen directly.

February 4, 2022

Immune checkpoint inhibitors (ICI), which help immune T cells identify and kill tumor cells, are most effective in patients who have tumor antigen-specific T cells in circulation. Studies have shown that patients with ovarian cancer do have such tumor-reactive T cells in their blood, indicating a “naturally occurring, antitumor immune response.” So why do only 10-15% of ovarian cancer patients respond favorably to ICI therapy? This was the question former Damon Runyon Clinical Investigator Ronald J. Buckanovich, MD, PhD, and his team at the University of Pittsburgh set out to answer in a recent study.

January 28, 2022

The Damon Runyon Cancer Research Foundation has announced its newest cohort of Damon Runyon Fellows, 13 outstanding postdoctoral scientists conducting basic and translational cancer research in the laboratories of leading senior investigators. This prestigious, four-year Fellowship encourages the nation's most promising young scientists to pursue careers in cancer research by providing them with independent funding ($231,000 total) to work on innovative projects.

January 24, 2022

A growing body of evidence links the gut microbiome—the vast collection of bacteria and other microorganisms that live in the digestive tract—to the body’s immune response to cancer. But the role of specific bacteria, and the nature of their interaction with immune cells, remain a critical subject of research. A better understanding of the crosstalk between the gut microbiota and the immune system would allow us, among other strategies, to use probiotics as part of cancer treatment.

January 18, 2022

‘‘All happy families are alike; each unhappy family is unhappy in its own way.’’ This principle, borrowed from Leo Tolstoy, is how Damon Runyon alumni Pavan Bachireddy, MD, and Catherine J. Wu, MD, summarized the conditions of immunotherapy response and resistance in a recent study.

January 10, 2022

Current imaging technology allows scientists to view tissue samples at such high resolution that they can gather information about individual cells. Looking at a high-resolution image of a tumor, for example, an oncologist can locate and measure the amount of a specific mutant protein in a cancer cell. The information gleaned from image-based single-cell analysis can aid both in diagnostics and tracking disease progression.