We investigate the contributions of inflammation in diseases or injuries that affect the nervous system. One of the most important concepts in science that has been translated into medical practice was pioneered by scientists at The Feinstein Institute and elsewhere: the proteins that cause inflammation, called cytokines, which are made by the body in response to infection or injury, are important in low levels to fight infection and help wound healing, while high levels of these same proteins can cause lasting damage to tissues and organs.

Spinal cord injury affects more than 10,000 Americans each year, often in the earliest phases of adulthood. It is well known that physical trauma to the spinal cord causes damage to nerves and other cells at the injury site. Over minutes to days, cells of the immune system are activated and release factors that cause inflammation, which is thought to play a pivotal role in tissue damage. One major focus of our lab is on understanding inflammation in spinal cord injury with the goal of learning how to support a less toxic environment to nerve cells after injury.

Another major project in the lab is to perform pre-clinical studies based on discoveries from Feinstein colleague Dr. Betty Diamond’s laboratory on the causes of lupus. Lupus is a chronic autoimmune disease that affects approximately 1.5 million Americans. The disease is characterized by the presence of antibodies against the patient, which can lead to inflammation in multiple organs, and is often accompanied by many symptoms, including those affecting the nervous system. This project, pursued together with Dr. Diamond and Feinstein colleague Dr. Yousef Al-Abed, aims to develop novel therapeutic agents for the treatment of lupus.

In addition to these pathological settings, we are also interested in understanding the molecules that the nervous and immune systems use to relay information under normal conditions.

Research Description

Research in the laboratory focuses on the impact of inflammation in the nervous system, in both acute and chronic settings. 

The role of cytokines in spinal cord injury and regeneration
Spinal cord injury (SCI) is a devastating condition that affects more than a quarter of a million Americans (www.spinalcord.uab.edu). Immediately after spinal cord injury, local and recruited immune cells produce high levels of pro-inflammatory cytokines. The resulting inflammation is thought to inhibit functional recovery.  Thus, current acute treatment for SCI aims to dampen inflammation, via the administration of steroids, which remains a controversial treatment recommendation due its failure to improve lasting functional recovery.  We are investigating the role of immune cells and their products such as cytokines on spinal cord injury and recovery. Neutralizing cytokines lessens inflammation in multiple disease models and therefore, in collaboration with Feinstein colleagues Dr. Yousef Al-Abed and Dr. Christine Metz, we are investigating the impact of modulating cytokine activity on SCI. We are studying the cellular and molecular pathways of cytokine expression during SCI and regeneration, and the impact of specifically modulating these pathways on the extent and time course of recovery after SCI.
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Rational Drug Design in Lupus

Lupus is a chronic autoimmune disease characterized by the presence of autoantibodies, many of which are directed against DNA and may cross-react with other antigens. These autoantibodies circulate as immune complexes, and activate immune cells or deposit in various organs where they mediate chronic inflammation leading to organ damage. In addition to severe kidney disease, 20-80% of lupus patients are subject to a variety of neuropsychiatric symptoms including depression, cognitive impairment, and seizures. Dr. Betty Diamond’s lab recently showed that a high proportion of anti-DNA antibodies present in lupus that cause kidney symptoms also recognize the NMDA receptor and therefore may contribute to neuropsychiatric symptoms.  In collaboration with Dr. Diamond and Feinstein colleague Dr. Yousef Al-Abed, we are investigating the molecular nature of the antigen-antibody recognition process of lupus autoantibodies in order to promote rational drug design of novel therapeutics for lupus.

Lab Member

Name:   Angelo Papatheodorou
Position:   Research Assistant 
Email:   apapaathe@nshs.edu
 

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