Patrick Sullivan, PhD

Associate Professor in Medicine, Geriatrics
Campus mail 508 Fulton St., Grecc 182, Durham, NC 27705
Phone (919) 286-0411
Email address p.sullivan@duke.edu

The primary focus of my lab is to investigate the relationship between APOE genotype and late onset Alzheimer’s disease (AD).  The single most common and influential gene in AD is the APOE gene.  The APOE gene is polymorphic; encoding three different alleles designated APOE2, E3 or E4.  APOE4 carriers have the highest risk for AD while APOE3 carriers have an essentially neutral risk and APOE2 carriers may be protected against AD.  The APOE4 gene is also linked to increased risk for atherosclerosis, cerebral amyloid angiopathy, peripheral neuropathy, multiple sclerosis, stroke and type II diabetes; as well as an increased susceptibility to HIV and Chlamydia infections, head injury and cognitive decline following coronary bypass surgery.  The fact that 28% of the US population are carriers of the APOE4 gene, underscores the need for a better understanding of APOE’s relationship to disease.  The major challenge facing researchers today is determining why some APOE4 carriers succumb to disease while others do not.  Genetic modifiers and environmental risk factors likely explain different individual outcomes. The primary environmental risk factors are thought to be; a Westernized diet, low physical activity, chronic stress, poor sleep habits, andro/menopause and most importantly, age.

We are currently working to test novel drug formulations that specifically target putative apoE dependent mechanisms involved in neurodegeneration.  Our initial screens involve neuronal-glial cell culture models that eventually will lead to testing in animals.  We currently use the best available animal model of apoE-linked AD, the human apoE targeted replacement (TR) or “knock in” mice.  I created three lines of human apoE TR mice, each expressing one the three human apoE isoforms and have since made multiple crosses to other AD related genes (e.g. APP, PS1 and tau).  I have given the apoE TR mice and made the crosses available to over 70 labs worldwide.

We are also working to build a better model of late onset AD by combining the apoE TR mice with non-mutated human APP and tau KI mice.  We think this is important because over 98% of all AD cases contain no mutations in the APP or tau genes.  Our hope is to better understand the true etiology and progression of late onset AD.  If successful this new model should aid in both novel target identification and new drug testing to produce therapeutics with greater efficacy in treating AD.

Education and Training

  • Ph.D., University of North Carolina at Chapel Hill, 1993

Publications

Shelton, SB, Pettigrew, DB, Hermann, AD, Zhou, W, Sullivan, PM, Crutcher, KA, and Strauss, KI. "A simple, efficient tool for assessment of mice after unilateral cortex injury." Journal of Neuroscience Methods 168, no. 2 (March 2008): 431-442.

PMID
18164073
Full Text

Ding, J-D, Lin, J, Mace, BE, Herrmann, R, Sullivan, P, and Bowes Rickman, C. "Targeting age-related macular degeneration with Alzheimer's disease based immunotherapies: anti-amyloid-beta antibody attenuates pathologies in an age-related macular degeneration mouse model." Vision Research 48, no. 3 (February 2008): 339-345.

PMID
17888483
Full Text

Malek, G, Jamison, JA, Mace, B, Sullivan, P, and Rickman, CB. "ERG responses and microarray analysis of gene expression in a multifactorial murine model of age-related retinal degeneration." Adv Exp Med Biol 613 (2008): 165-170.

PMID
18188941
Full Text

Osorio, C, Sullivan, PM, He, DN, Mace, BE, Ervin, JF, Strittmatter, WJ, and Alzate, O. "Mortalin is regulated by APOE in hippocampus of AD patients and by human APOE in TR mice." Neurobiol Aging 28, no. 12 (December 2007): 1853-1862.

PMID
17050040
Full Text

Manelli, AM, Bulfinch, LC, Sullivan, PM, and LaDu, MJ. "Abeta42 neurotoxicity in primary co-cultures: effect of apoE isoform and Abeta conformation." Neurobiology of Aging 28, no. 8 (August 2007): 1139-1147.

PMID
16837105
Full Text

Wang, H, Durham, L, Dawson, H, Song, P, Warner, DS, Sullivan, PM, Vitek, MP, and Laskowitz, DT. "Corrigendum to "an apolipoprotein e-based therapeutic improves outcome and reduces alzheimer's disease pathology following closed head injury: Evidence of pharmacogenomic interaction". [Neuroscience 144 (2007) 1324-1333]{star, open} (DOI:10.1016/j.neuroscience.2006.11.017)." Neuroscience 146, no. 2 (May 11, 2007): 874-null.

Full Text

Mihovilovic, M, Robinette, JB, DeKroon, RM, Sullivan, PM, and Strittmatter, WJ. "High-fat/high-cholesterol diet promotes a S1P receptor-mediated antiapoptotic activity for VLDL." J Lipid Res 48, no. 4 (April 2007): 806-815.

PMID
17264352
Full Text

Mace, BE, Wang, H, Lynch, JR, Moss, J, Sullivan, P, Colton, H, Morgan, K, Renauld, J-C, and Laskowitz, DT. "Apolipoprotein E modifies the CNS response to injury via a histamine-mediated pathway." Neurological Research 29, no. 3 (April 2007): 243-250.

PMID
17509222
Full Text

Wang, H, Durham, L, Dawson, H, Song, P, Warner, DS, Sullivan, PM, Vitek, MP, and Laskowitz, DT. "An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: evidence of pharmacogenomic interaction." Neuroscience 144, no. 4 (February 23, 2007): 1324-1333.

PMID
17187933
Full Text

Yun, SH, Park, KA, Kwon, S, Woolley, CS, Sullivan, PM, Pasternak, JF, and Trommer, BL. "Estradiol enhances long term potentiation in hippocampal slices from aged apoE4-TR mice." Hippocampus 17, no. 12 (January 2007): 1153-1157.

PMID
17696167
Full Text

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