Research
Joyce A. DeLeo, Ph.D.
Principle Investigator
Dr. DeLeo received her B.S. in Biology and Chemistry from the State University of New York at Albany in 1982. She decided to pursue a career in pharmacology and was accepted into the graduate program at University of Oklahoma Health Sciences Center (O.U.). She did much of her pre-doctoral research at the Max Planck Institute of Psychiatry in Martinsried, W. Germany under a Fulbright scholarship investigating the effect of cerebral ischemia on an electrophysiological hippocampal slice preparation and the pharmacological intervention of in vivo ischemia. She received her Ph.D. from O.U. in January 1988 and accepted a post-doctoral fellowship at Harvard University, Department of Neuroscience, where she studied the effects of neonatal hypoxia and seizure susceptibility. She then came to Dartmouth as a post-doctoral fellow in the Anesthesia Research Laboratory and was appointed as an Instructor of Anesthesiology and Pharmacology in July 1989, being promoted to Assistant Professor in 1991, Associate Professor in 1998 and Professor in 2003. In 2003 she was appointed Vice Chair of Pharmacology & Toxicology and the Irene Heinz Given Endowed Professor of Pharmacology in 2005. Dr. DeLeo was then appointed Chair of Pharmacology & Toxicology in July 2008.
Dr. DeLeo has been instrumental in developing and directing the Neuroscience Center at Dartmouth
Research Areas:
The mission of Dr. DeLeo’s laboratory is to create a better understanding of central nervous system mechanisms that lead to chronic pain including neuropathic, inflammatory, post-operative and low back pain. This knowledge will translate into development of new, effective approaches for treatment and even prevention of these chronic pain syndromes. The pain that follows peripheral nerve or root injury is chronic and consistently refractory to available treatments and analgesics. These neuropathic and low back pain syndromes include deafferentation pain, HIV, diabetic, cancer and ischemic neuropathies, phantom limb pain, trigeminal neuralgia, postherpetic neuralgias, nerve injury caused by surgery or trauma and low back pain due to herniated discs (radicular pain).
The central nervous system (CNS) was long considered an immunological priviledged site, a place wherein the immune system performed few functions. Over the past decade this view has altered dramatically. The CNS is actively involved in immunological phenomena that are both physiological and pathological. Work in this laboratory has focused on the mechanisms by which inflammation develops in the CNS in response to distant peripheral nerve injury or central root injury. The broad, long-term objective of Dr. DeLeo’s research is to elucidate mechanisms responsible for the generation and maintenance of chronic pain. Toward this end, the DeLeo group has developed and characterized rodent models of neuropathic (peripheral nerve injury) and radicular (root injury) pain. These models have proved ideal for the study of chronic pain due to the creation of predictable and robust behavioral and neurochemical end-points. Using these models, they first found evidence that glial reactivity and immune cell products (e.g. cytokines/chemokines) contribute to the generation of chronic pain states. The DeLeo laboratory has strong evidence for a CNS role of glia, namely astrocytes and microglia in the etiology of numerous pain states. The laboratory uses behavioral pharmacology, molecular biology, immunohistochemistry, Western Blot analyses, FACs, RT-PCR, and enzyme-linked immunosorbent assays (ELISA) in both experimental animal models and in human clinical studies. In their dissection of these immunological distinct systems, they investigate topics relative to both the innate and adaptive arms of immunity including: cell migration and trafficking, proliferation, adhesion molecule expression, antigen presentation, and cytokine/chemokine release and production. They utilize both in vivo and in vitro methods in parallel to answer specific question related to neuroimmune reactivity and neuroinflammation: trafficking of peripheral leukocytes into the CNS after injury.
The CNS broadly responds similarly, albeit not exactly in an immunologic fashion to autoimmunity, trauma, brain abscess and peripheral nerve or root injury that leads to chronic pain. For the first time, the mechanisms of CNS cellular activation, chemokine elaboration, and leukocyte trafficking in CNS reactions following peripheral nerve, nerve root injury and xenobiotic administration including opioids and cannabinoids are directly compared using identical methodologies. These studies have broad implications to other CNS diseases such as multiple sclerosis, HIV-dementia and Alzheimer’s disease.