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

Trommer, BL, Shah, C, Yun, SH, Gamkrelidze, G, Pasternak, ES, Stine, WB, Manelli, A, Sullivan, P, Pasternak, JF, and LaDu, MJ. "ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42." Neurobiology of Disease 18, no. 1 (February 2005): 75-82.

PMID
15649697
Full Text

Walsh, MM, Malek, G, Saloupis, P, Sullivan, PM, Mace, B, Schmechel, DE, Rickman, CB, and Rickman, DW. "Apolipoprotein (APOE) allelic expression, advanced age, and diet contribute to atrophic degenerative changes in retinal ganglion cells and optic nerve in a mouse model: Predictors of severity of glaucoma?." 2005.

Scholars@Duke

Trommer, BL, Shah, C, Yun, SH, Gamkrelidze, G, Pasternak, ES, Ye, GL, Sotak, M, Sullivan, PM, Pasternak, JF, and LaDu, MJ. "ApoE isoform affects LTP in human targeted replacement mice." Neuroreport 15, no. 17 (December 2004): 2655-2658.

PMID
15570172
Full Text

Murphy, GM, Mitrasinovic, OM, and Sullivan, PM. "P2-293 Microarray comparison of gene expression in the hippocampus of aged apoE E3 and E4 transgenic mice.": Elsevier BV, July 2004.

Full Text

Blain, J-F, Sullivan, PM, and Poirier, J. "P2-085 Response to brain injury in human apolipoprotein E targeted replacement mice is genotype-specific.": Elsevier BV, July 2004.

Full Text

Sullivan, PM, Mace, BE, Maeda, N, and Schmechel, DE. "Marked regional differences of brain human apolipoprotein E expression in targeted replacement mice." Neuroscience 124, no. 4 (January 2004): 725-733.

PMID
15026113
Full Text

Lynch, JR, Tang, W, Wang, H, Vitek, MP, Bennett, ER, Sullivan, PM, Warner, DS, and Laskowitz, DT. "APOE genotype and an ApoE-mimetic peptide modify the systemic and central nervous system inflammatory response." J Biol Chem 278, no. 49 (December 5, 2003): 48529-48533.

PMID
14507923
Full Text

DeKroon, RM, Mihovilovic, M, Goodger, ZV, Robinette, JB, Sullivan, PM, Saunders, AM, and Strittmatter, WJ. "ApoE genotype-specific inhibition of apoptosis." Journal of Lipid Research 44, no. 8 (August 2003): 1566-1573.

PMID
12754278
Full Text

Malek, G, Sullivan, PM, Mace, BE, Schmechel, D, and Rickman, CB. "Effect of diet and targeted replacement human APOE isoforms in aged mice." May 2003.

Scholars@Duke

Hinsdale, ME, Sullivan, PM, Mezdour, H, and Maeda, N. "ApoB-48 and apoB-100 differentially influence the expression of type-III hyperlipoproteinemia in APOE*2 mice." Journal of Lipid Research 43, no. 9 (September 2002): 1520-1528.

PMID
12235184
Full Text

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