Graduate Studies Faculty

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Jeffrey Iliff, Ph.D.

Assistant Professor
Admin Unit: SOM-Anesthesiology and Peri-Operative Medicine Department
Phone: 503-494-4047
Office: HRC 561
Mail Code: HRC5N
Neuroscience Graduate Program
Research Interests:
Glial cell biology, cerebrovascular physiology, CSF circulation, glymphatic system, Alzheimer's disease, traumatic brain injury, TBI, 2-photon microscopy, aquaporin-4, AQP4, systems, Neurobiology of Disease » PubMed Listing
Preceptor Rotations
Dr. Iliff has not indicated availability for preceptor rotations at this time.
Faculty Mentorship
Dr. Iliff is available as a mentor for 2016-2017.

The cerebral vasculature is the crossroads of the brain, the site of nutrient delivery to and waste clearance from the CNS, ion and water homeostasis, and peripheral immune surveillance of the brain and spinal cord. The neurogenic niche is maintained within perivascular spaces, while the cerebral vasculature is the site of tumor cell entry into and migration through the brain, amyloid beta deposition in Alzheimer’s disease and cerebral amyloid angiopathy, cerebral edema formation and resolution after stroke and traumatic brain injury (TBI), and peripheral leukocyte infiltration in multiple sclerosis. Research in my lab centers upon this crossroads of the CNS, seeking to define the ways that different cell types (including astrocytes, endothelial cells, pericytes, vascular smooth muscle cells, and others) function in concert to maintain brain function, and how these interactions break down in the setting of pathology. Work in my lab can be broken down into three general domains:

Substrates of age-related vulnerability to amyloid beta deposition and development of Alzheimer’s disease

Neurodegenerative diseases such as Alzheimer’s disease are conditions of the aging brain, yet it is unclear what changes occur in the aging brain that render it vulnerable to the mis-aggregation of amyloid beta and the development of neurodegeneration. Over the past 5 years, we have defined a brain-wide paravascular pathway, termed the ‘glymphatic system’ , that functions as the brain’s waste clearance system, eliminating proteins such as amyloid beta and tau (two pathogenic proteins in Alzheimer’s disease) from the brain interstitium. Glymphatic pathway function is impaired in the aging brain, slowing the clearance of amyloid beta. Ongoing work in my lab is seeking to define the cellular and molecular changes that occur in the aging brain that cause the glymphatic pathway fail, and how those changes might be reveres in the prevention or treatment of Alzheimer’s disease.

Defining the mechanism driving the development of post-traumatic neurodegeneration

TBI is an established risk factor for the development of dementia, including Alzheimer’s disease, which incidence of Alzheimer’s doubling among subjects suffering a substantial TBI early in life. More recent clinical data suggests that even mild TBI (concussion), is associated with an increased risk of early onset dementia. However, it is unclear what takes place in the young post-traumatic brain that appears to set the stage for neurodegeneration later in life. We have reported that after experimental TBI, glymphatic pathway function is impaired, which appears to be underpinned by mis-regulation of an astroglial water channel, aquaporin-4 (AQP4). Ongoing work in my lab is attempting to define the role that AQP4 mis-regulation after TBI has in promoting the aggregation of the protein tau into neurofibrillary tangles and accelerating neurodegeneration in the post-traumatic brain. We are further evaluating whether targeting AQP4 pharmacologically can slow or halt the development of post-traumatic neurodegeneration.


Improving neurotherapeutics delivery to the CNS, through or around the blood brain barrier

The blood brain barrier (BBB) presents a substantial obstacle for the treatment of disease in the CNS. Particularly in the case of recently developed biological therapeutics (such as recombinant enzymes or designer antibodies), un-aided transit through the blood brain is for practical purposes impossible. Several approaches to circumventing the BBB have been developed and are either in clinical use or are under development, including osmotic BBB disruption pioneered by Dr. Ed Neuwelt here at OHSU, intrathecal or intracerebroventricular drug delivery through the cerebrospinal fluid (CSF), or through the use of ‘trojan horse’ strategies to coopt BBB import receptors to transport drug into the brain. However, once these macromolecular therapeutics are able to cross or bypass the BBB, little is known about the physiological and pathophysiological factors that influence drug distribution through the brain parenchyma. Work within my group is seeking to define what biological processes govern CSF and interstitial fluid circulation through the brain and how these processes can be modulated to improve pharmaco-distribution through the CNS.