Courses Taught
- Integrated Human Anatomy and Physiology A (HLTH 301 )
- Integrated Human Anatomy and Physiology B (HLTH 302)
- Special Topics in Health Sciences: Molecular Mechanisms of Human Disease (HLTH 380 )
- Health Research Literacy (HLTH 202)
Research Interests
Our laboratory is broadly interested in the identification and characterization of molecular mechanisms underlying various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and traumatic brain injury. While the particular toxic insult necessarily varies with disease, this diverse group of brain disorders shares a common neuropathologic hallmark:
neuroinflammation. Although the process of inflammation is not intrinsically harmful, persistent or disproportionate inflammatory responses can be deleterious, especially in the central nervous system. Critical inflammatory activities in the healthy brain are mediated by microglia and astrocytes, and it is dysfunctional responses from these integral innate immune cellular effectors that drive neuroinflammation in disease. Of particular interest to our work,
APOE is a polymorphic gene in humans known to differentially modulate microglial and astrocyte function. Indeed, inheritance of the
APOE allelic variant epsilon4 represents the single greatest genetic risk factor for development of Alzheimer's disease, and predicts the severity and outcome of many other neurodegenerative diseases. This suggests that
APOE may exert its pathologic influence in part by disrupting normal inflammatory processes in the brain. As experimentalists, we use a variety of biochemical,
in vitro,
in vivo, and behavioral approaches to investigate the precise role that
APOE plays in human brain disease.
Recent PublicationsGraykowski D, Cudaback E. (2021) Don't know what you got till it's gone: microglial depletion and neurodegeneration. Journal of Neuroregeneration. 16(10):1921-1927.
Graykowski D, Kasparian K, Caniglia J, Gritsaeva Y, Cudaback E. (2020). Neuroinflammation drives APOE genotype-dependent differential expression of neprilysin. Journal of Neuroimmunology July 4; 346:577315. doi: 10.1016/j.jneuroim.2020.577315.
Yang Y, Keene CD, Peskind ER, Galasko DR, Hu SC, Cudaback E, Wilson AM, Li G, Yu CE ,Montine KS, Zhang J, Baird GS, Hyman BT, Montine TJ (2015) Cerebrospinal fluid particles in Alzheimer's disease and Parkinson's disease. J Neuropathol Exp Neurol 74(7):672-87.
Wang DB, Kinoshita Y, Kinoshita C, Uo T, Sopher BL,
Cudaback E, Keene CD, Bilousova T, Gylys K, Case A, Jayadez S, Wang HG, Garden GA, Morrison RS (2015) Loss of endophillin-B1 exacerbates Alzheimer's disease pathology.
Brain 138(7):2005-19.
Melief EJ,
Cudaback E, Jorstad NL, Sherfield E, Postupna N, Wilson A, Darvas M, Montine KS, Keene CD, Montine TJ (2015) Partial depletion of striatal dopamine enhances penetrance of cognitive deficits in a transgenic mouse model of Alzheimer's disease.
J Neurosci Res 93(9)1413-22.
Cudaback E, Yang Y, Li X, Montine KS, Montine TJ, Keene CD (2015) APOE genotype-dependent modulation of astrocyte chemokine CCL3 production.
Glia. 63(1):51-65.
Yang Y, Aloi MS,
Cudaback E, Josephsen SR, Rice SJ, Jorstad NL, Keene CD, Montine TJ (2014) Wild-type bone marrow transplant partially reverses neuroinflammation in progranulin-deficient mice.
Lab Invest. 94(11):1224-36.