Research: Discovering Novel, More Accurate and Less Invasive Ways to Diagnose Disease
Identifying Biomarkers of Neurological Diseases

SNIP researchers are leading the efforts in biomarker discovery, a process that focuses on isolating circulating factors in the bloodstream or urine, as well as genetic variations, that relate to specific characteristics of vascular malformations or tumors in patients. Biofluids (blood and urine) are obtained from patients prior to and following treatment and/or removal of their vascular malformation or tumor. Differences in biomarkers before and after treatment are also being related to tissue obtained from surgery to obtain more information about these diseases and to design better treatment. For example, Dr. Steven D. Chang hopes to one day offer his patients a simple blood test that he can use to determine whether a particular patient will benefit from neurosurgery versus radiosurgery. The ultimate goal is to practice personalized medicine, which Dr. Chang calls "the right treatment, in the right patient, at the right time."

Understanding Normal and Abnormal Blood Vessel Growth in the Brain

Image of new blood vessel growth visualized with fluorescent probes.

Blood vessels bring oxygen- and nutrient containing blood to the entire body; however the vessels of the brain are unique from those of the rest of the body, in that they possess a selective ‘gate’ for what goes in and out of the brain, called the blood-brain-barrier. The brain is highly reliant on proper blood flow – while only about 2% of the body mass, the brain consumes 20% of the oxygen. Understanding the process by which blood vessels form, respond to damage, and repair themselves is important for research on:

  • Vascular malformations, characterized by overgrowth or dysfunction of the vessels, as seen in arteriovenous malformations, aneurysms, and Moyamoya Disease
  • Brain tumors, which recruit new blood vessel formation to feed the growing tumor
  • Stroke, the recovery from which depends in part on new blood vessel growth restoring blood flow to vulnerable areas of brain

Elucidating the Connection Between Tumors, Stem Cells and Blood Vessels

Normal human brain tissue: Neural stem cells (green) are organized in a niche that surrounds a blood vessel (V).

Adult stem cells are capable of self-renewal and of producing other types of cells, making them valuable players in repair strategies. Researchers are interested in directing a patient’s own stem cells to regenerate damaged or diseased tissue and restore health.

The ability of stem cells in the brain (called neural stem cells) to regenerate themselves and to produce the cell types of the brain is partly guided by signals from neighboring cells, in particular the cells that make up blood vessels. In fact, recent research has shown that normal neural stem cells are located in a niche surrounding blood vessels. SNIP researchers are currently studying the signals that control this process to understand how these cells function in disease and in normal repair.

Human brain tumor tissue: Cancer stem cells (green) are organized in a niche around the tumor blood vessel (V).

SNIP researchers have succeeded in isolating cells that resemble neural stem cells from brain tumor tissue obtained from patients treated at Stanford. Similar to neural stem cells, these tumor cells are located around the blood vessels that feed the tumor, suggesting there might be a crucial interaction. Understanding this relationship in a healthy brain may shed some light on what occurs in disease. Using the latest genetic and proteomic technologies to determine what changes occurred in these cells to cause them to produce or promote disease, it may soon be possible for SNIP researchers to design new therapies for affected patients, prevent recurrent tumor growth, identify genetic risk factors among family members, and develop preventative therapies to protect at-risk family members against development of disease.

Dr. Steven D. Chang (on right) demonstrates the CyberKnife Radiosurgery arm developed at Stanford.

Moving Toward More Personalized and Effective Treatment

Noninvasive targeting of the brain and spinal cord with directed beams of radiation (called radiosurgery) is used to treat vascular malformations, brain tumors, movement disorders, and psychiatric conditions. Although it is not well understood why some people respond better to radiosurgery than others, Dr. Chang is leading SNIP’s efforts to understand the biology behind these differences in radiation sensitivity in patients with vascular malformations and brain tumors. His group is examining genetic variations and protein expression in patients undergoing radiosurgery, to understand the biology behind these variations in patient response. The ultimate goal is to develop more personalized diagnoses and treatment plans.

Bringing Technology to the Bedside: Using Nanotechnology and Microfluidics to Transform Patient Care

Microfluidic biochips and nanotechnology have the potential to transform the future of neuroscience research and patient care.

Microfluidic biochips and nanotechnology have the potential to transform the future of neuroscience research and patient care. How do basic research experiments occurring on the lab bench best evolve into an easy-to-use, robust, and transportable clinical test? Miniaturizing the research experiment is the goal of microfluidic systems, which can be designed to perform these research experiments on a small chip no larger than the size of a standard glass slide - processes that usually require a laboratory full of equipment. Microfluidic technologies can be completely automated, which enables point-of-care use, particularly in clinical and resource-limited settings where samples need to be processed immediately and in a standardized fashion. For example, some studies require isolation of pure cell populations from the blood. SNIP researchers and collaborators have succeeded in developing miniaturized, microfluidic technologies for sorting these cells from the blood quickly and easily. This technology was validated in a large-scale collaborative project funded by an NIH grant to evaluate inflammation in Intensive Care Unit patients. Results show that this technology performs favorably in comparison to manual processing in large-scale laboratories and can be easily implemented in the clinical setting. SNIP researchers are focusing on the development of new biochips to isolate specific cell populations and to identify biomarkers. These tools will enable SNIP clinicians to improve the diagnosis and treatment decisions for patients affected by neurological conditions.