Humans are visual creatures, hardwired to respond to shapes, colors, lines and movement. In the complex world of biomedical research, where the objects of study are often infinitesimally small, scientists and physicians use sophisticated imaging technologies to better understand and perform their work — often with strikingly beautiful results.

STRESSED OUT

The links between stress and cancer remain unclear, though most scientists believe a connection exists. At the level of cells, metabolic stress — a condition caused by abnormal changes in the levels or amounts of nutrients — almost certainly can contribute to cells' transformation from normal to malignant. City of Hope neuroscientists use green fluorescent protein to monitor metabolic stress levels in cells of the nervous system.

In the cluster of nerve cells seen here, those near the outer regions undergo significant metabolic stress (green) as they begin forming strands of nerve cells called axons (red). Monitoring cells' metabolic stress levels can help researchers understand how stress may lead to abnormal cell growth and cancer.

TOTALLY RAD

Drugs and radiation therapy can kill cancer, but they also damage normal tissue, causing side effects.

In bone marrow transplantation, patients receive both chemotherapy and high-dose radiation therapy to clear all traces of their disease, but that can prove challenging for patients. As technology has evolved, radiation oncologists have found ways to narrowly focus and target therapeutic beams to the cancer, minimizing its effects on healthy tissue.

Now, through image-guided targeted therapies such as TomoTherapy, specialists in City of Hope's Department of Radiation Oncology can plan their treatments to sculpt their beams and deliver varying amounts of radiation, ranging from light (green) to moderate (yellow) to intense (red), exclusively to diseased tissue. Healthy tissues (gray) get no exposure.

MUSCLE IN

City of Hope scientists are delving into the intricacies of muscle cell metabolism to understand how those cells gain nutrients, generate energy and develop into muscle tissue. Janice Huss, Ph.D., assistant professor in the Department of Diabetes and Metabolic Diseases Research at City of Hope, and her team used three fluorescent dyes — red, green and blue — to visualize different parts of muscle cells, called myocytes, as they fuse together to form myotubes, the basic structures of muscle tissue.

The blue dye stains DNA in the oval nuclei. Red shows mitochondria, the power generators of cells, which are actively producing energy. Green marks a protein called PGC-1a, which controls genes that are important in muscle cell metabolism. The researchers' work could lead to a better understanding of the factors contributing to muscle diseases, including heart disease, as well as diabetes and other metabolic syndromes.

RESISTANCE IS FUTILE

Cancer often grows resistant to powerful drugs, and City of Hope scientists such as Susan Kane, Ph.D., professor in the Division of Tumor Cell Biology, vigilantly search for clues as to why and how breast cancer cells learn to outwit these treatments.

For patients treated with the targeted therapy trastuzumab, also called Herceptin, a key protein called phospho-CREB may be involved with drug resistance. Using antibodies that stick to phospho-CREB and make it appear dark brown, the scientists probed tumor samples taken before (top) and after Herceptin treatment. They found much more phospho-CREB following treatment in many of the patients. The results appear to confirm that cancer cells react to Herceptin by increasing their production of phospho-CREB and that the protein may somehow play a role in building resistance to the drug.

COURTESY OF SUSAN KANE/DIVISION OF TUMOR CELL BIOLOGY

WORKING TOGETHER

City of Hope researchers have found that a protein called STAT3 plays a vital role in boosting cancer cell growth and development. To better understand where STAT3 travels in the cell and how it gets there, scientists look for other molecules that might work alongside STAT3, such as a protein called v-Src.

The researchers tagged STAT3 with a yellow fluorescent protein and v-Src with a compound that glows red when hit by laser light. (A dark blue fluorescent dye marks the cell's DNA.) The two proteins were found in the same areas of the cell, indicating they likely work together. Finding these interactions could point to potential new drug targets for future study.

TWISTED

City of Hope researchers led by Carlotta Glackin, Ph.D., associate professor in City of Hope's Department of Neurosciences, study cancer with a TWIST.

Looking for the factors that lead to the spread of breast cancer, the team's work has pointed to the TWIST protein, which plays a key role in stem cell development and also occurs in high levels in metastatic breast cancers. Looking for clues to how TWIST works, the scientists tagged the protein with a pink dye and tagged another protein, called F-actin, with a green dye. F-actin helps make up the skeleton cells, and the researchers wanted to know if TWIST affects the shape of cancer cells in a way that could help them migrate away from the original tumor and establish new tumors in the body.

GRUMPY OLD NEURONS

The brain develops from the inside out. Nerve cells, or neurons, first develop in the lower layers of the brain. The newly generated cells then are pushed toward the brain's outer regions, passing the older neurons. The youngest neurons find themselves nearest the brain's surface. City of Hope researchers under the direction of Qiang Lu, Ph.D., associate professor in the Department of Neurosciences, use dyes that help them distinguish between older neurons (pink) and younger neurons (green), so they can see where each type ends up at different stages of development. Observing this process could help scientists understand what might go wrong and lead to brain cancer as well as neurological diseases such as Parkinson's and Alzheimer's diseases.

THE RIGHT PATH

Pathologists, doctors who study blood, fluid or tissue to diagnose disease, can trace the beginnings of their discipline at least as far back as the early 19th century. Despite significant advances in technology since then, cancer still must be diagnosed by a pathologist peering through a microscope. These highly skilled experts rely on distinct visual cues from stained tissue samples to determine if cancerous cells are present and to what stage the disease has developed.

As technology advances, however, new tools allow pathologists to determine more subtle characteristics of a patient's disease. For example, nearly all cervical cancers arise from human papillomavirus, or HPV, but the virus comes in many different strains. The two most common strains are HPV16 and HPV18. New laboratory techniques enable pathologists to determine if a cervical cancer was caused by HPV16 (top) or HPV18. This type of insight one day may guide oncologists and patients in their treatment choices.

COURTESY OF SHARON WILCZYNSKI/DEPARTMENT OF PATHOLOGY

MERLIN MAGIC

Scientists call it transformation. It is the mysterious process that pushes cells from normal to cancerous. The term implies an almost magical change, one that Toshifumi Tomoda, M.D., Ph.D., assistant professor of neurosciences at City of Hope, aims to demystify by studying a protein fittingly called Merlin.

Also known as neurofibromin 2 or schwannomin, Merlin (green) can cause tumors in the nervous system when it is mutated. When it undergoes a chemical change through an enzyme called ULK1/ATG1 (red), Merlin can cause cells to abnormally change their shape. By tracking ULK1/ATG1 and Merlin in cells, researchers hope to better understand their interaction and the events leading up to cancer.