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Areas of Ongoing Clinical Research

Helping the Eye Repair Itself
The retina is the light-sensitive layer of delicate nervous tissue that lines the inside of the eye and sends visual messages through the optic nerve to the brain. If lifted or pulled from its normal position, the retina can detach, causing permanent vision loss if not promptly treated. Surgery is often used to reattach the retina, but some vision loss typically remains, frustrating ophthalmologists and patients alike. Columbia ophthalmologist Dr. Stephen Tsang is working with embryonic stem cells to develop regenerative capabilities in mouse models with retinal degenerations. Dr. Tsang and his research team, from Columbia's Harkness Eye Institute, believe that if they can uncover how stem cell-derived retinal neurons communicate, the findings may also impact other neurodegenerative diseases such as Alzheimer's and Parkinson's.

Shedding Light on the Relationship Between Gum and Heart Disease
Investigators at Columbia's College of Dental Medicine and College of Physicians & Surgeons have studied animal models to better understand the relationship between plaque deposits on teeth and fatty deposits that can grow in blood vessels. These fatty deposits can lead to atherosclerosis, a narrowing of the blood vessels that significantly increases the risk of heart attack or stroke. The researchers demonstrated a plausible 'smoking gun' link between gum disease and atherosclerosis by showing that P. gingivalis-bacteria implicated in the gum disease periodontitis-escalates the process of plaque build-up in the arteries of mice. Based on this finding, the Columbia team conducted studies in human patients that confirmed the link between periodontal bacteria and atherosclerosis. This research, reported in 2005, may ultimately help physicians and dentists identify patients at-risk for heart disease who would not otherwise be so considered.

Improving In Vitro Fertilization
Columbia researchers, led by Dr. Joyce Lustbader, are working to improve the protocols currently used in vitro fertilization (IVF) cycle. IVF is a complex process in which eggs are inseminated with sperm in a laboratory and the resulting embryos transferred to the woman's uterus for implantation with the ultimate goal of a successful pregnancy. IVF benefits many couples who have difficulty conceiving children by natural methods. Current research utilizing a mouse model may allow for significantly fewer hormone injections, which are required to stimulate the ovaries to increase egg production for IVF. Dr. Lustbader is also working with a rat model to prevent ovarian hyperstimulation syndrome (OHSS), a potentially serious outcome that can occur in women who are pursuing fertility treatments or those who have been egg donors.

New Hope For People With Anxiety Disorders
In the past, scientists were only able to view and understand anxiety solely as a product of fear, within the limited context of negative emotions. Now, using mouse models, a team of Columbia neurobiologists-including Nobel Laureate Eric Kandel and his colleague Michael Rogan-has turned conventional scientific wisdom on its head, uncovering deep within the brain an independent system associated with feelings of safety and security that may malfunction in people with anxiety disorders. The discovery of this "safety circuit" has shed greater light on the neurobiology of happiness and the anatomy of chronic anxiety. It also has opened up new and important avenues for more comprehensive treatments targeting anxiety disorders.

Understanding How the Brain Guides Our Judgment
How we interact with our world and make judgments about what we see has always been a source of mystery, but Columbia neuroscientists are doing exciting research to shed some light on the process. Based on research with rhesus monkeys, the team, led by Dr. C. Daniel Salzman, has demonstrated that nerve cells in the brain seem to function as part of a pathway that allows the brain to learn whether certain images are pleasant or unpleasant, and to respond appropriately. These findings have provided insight into aspects of emotional processes, visually based behavior and cognition in humans. In many neuropsychiatric disorders, such as mood and anxiety disorders, the neural circuits that link the sensory world to emotions become dysfunctional. By advancing our understanding of these processes, this work represents an important step towards understanding the pathophysiology of many neuropsychiatric illnesses.

Regulating a Receptor that Activates Life-Threatening Diseases
RAGE, a receptor that is highly active in inflammation and cancerous tumors throughout the body, was discovered by Columbia scientists through research involving rodents. Today, research is being conducted on many different diseases to try to inhibit the activity of the receptor. For example, Columbia researchers found that by inhibiting the activity of RAGE in certain cancers, tumor growth decreased. These researchers found that inhibiting RAGE also sharply limited the complications of diabetes in rodent models. Other key diseases being studied include Alzheimer's and other neurodegenerative diseases, bowel inflammation, vascular disease and liver disease.

Treating Acute Heart Failure
Columbia researchers have demonstrated the beneficial effects of biventricular pacing—simultaneous pacing of the left and right ventricles of the heart—in acute heart failure. Biventricular pacing helps the heart pump blood more efficiently and coordinates contractions between the ventricles. Coordinated pumping between the ventricles is vital as research has found that if synchronization is off just a fraction of a second, the result can be a 10 percent reduction in cardiac pumping output. Results of this research, conducted in pigs, support the hypothesis that biventricular pacing may be beneficial for people with acute heart failure following open heart surgery.

Developing New Treatments for Asthma and Allergy
Although many treatments are available for asthma and allergy, most have side effects and others do not work all the time. To develop new treatments, Columbia scientists studied a protein called STAT-6, which is essential for the development of allergy and asthma in mice. Their findings have identified more than 100 genes controlled by STAT-6. These genes may be important regulators of allergy and asthma and are potential targets for the development of new drugs to prevent these disorders.

Developing New Therapies for Depression
Depression is not just a case of the blues. Weeks, months or years of feeling sad, worthless and irritable can sap a personís interest in life, ruin family relationships and even ignite thoughts of suicide. Antidepressants are frequently effective at lifting sufferers out of depression, but they can take several weeks or even months to kick in. Columbia researchers are investigating how current therapies work in order to develop new treatments that work faster and more effectively. Recent experiments with mice have demonstrated how antidepressants alleviate depression by stimulating the growth of new neurons in the brain. The researchersí next challenges are to determine the role of these new neurons and why they lift mood—they hope the answers to these questions will put them on the path to developing new therapies for depression.

Achieving Greater Understanding of Alzheimer's Disease
Medical experts believe that being able to detect the very earliest stages of Alzheimer's disease may, in the future, enable them to prescribe medications to stop the progression of this disease before symptoms of dementia appear. Columbia researchers are studying the brain function of rodents, using imaging tools and measures of brain function to increase our understanding of a complex brain circuit that controls memory, and often fails early in people with Alzheimer's disease. In doing so, they have focused on particular neurons most vulnerable to early Alzheimer's and have begun isolating rogue molecules that cause memory decline during the course of the disease.

Testing the Safety of Cancer Treatments
Scientists at Columbia set out to examine the potential side effects of new cancer drugs, called angiogenesis inhibitors, designed to block the development of new blood vessels in tumors, thus starving the cancerous growths. Some cancer specialists were worried these treatments could interfere with normal blood vessel function or development, causing severe side effects. The results of their research found that blocking blood vessel development in healthy adult monkeys and mice appears to cause few side effects, indicating that they may be safe for widespread cancer treatment.
© 2005 Columbia University