Patrick Sullivan, PhD

Associate Professor of Medicine
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

Laskowitz, Daniel T., Pingping Song, Haichen Wang, Brian Mace, Patrick M. Sullivan, Michael P. Vitek, and Hana N. Dawson. “Traumatic brain injury exacerbates neurodegenerative pathology: improvement with an apolipoprotein E-based therapeutic..” J Neurotrauma 27, no. 11 (November 2010): 1983–95. https://doi.org/10.1089/neu.2010.1396.

PMID
20812776
Full Text

Lukiw, Walter J., Jian Guo Cui, Li Yuan Yuan, Partha S. Bhattacharjee, Madelyn Corkern, Christian Clement, Eli M. Kammerman, et al. “Acyclovir or Aβ42 peptides attenuate HSV-1-induced miRNA-146a levels in human primary brain cells..” Neuroreport 21, no. 14 (October 6, 2010): 922–27. https://doi.org/10.1097/WNR.0b013e32833da51a.

PMID
20683212
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Sullivan, P. M., B. Mace, R. Klein, and S. Moore. “LOSS OF SYNAPTIC INTEGRITY IN AGED APOE4 MICE.” Gerontologist 50 (October 1, 2010): 183–183.

Scholars@Duke

Bales, Kelly R., Feng Liu, Su Wu, Suizhen Lin, Deanna Koger, Cynthia DeLong, Jeffrey C. Hansen, Patrick M. Sullivan, and Steven M. Paul. “Human APOE isoform-dependent effects on brain beta-amyloid levels in PDAPP transgenic mice..” J Neurosci 29, no. 21 (May 27, 2009): 6771–79. https://doi.org/10.1523/JNEUROSCI.0887-09.2009.

PMID
19474305
Full Text

Korwek, Kimberly M., Justin H. Trotter, Mary Jo Ladu, Patrick M. Sullivan, and Edwin J. Weeber. “ApoE isoform-dependent changes in hippocampal synaptic function..” Mol Neurodegener 4 (May 27, 2009). https://doi.org/10.1186/1750-1326-4-21.

PMID
19725929
Full Text

James, Michael L., Patrick M. Sullivan, Christopher D. Lascola, Michael P. Vitek, and Daniel T. Laskowitz. “Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage..” Stroke 40, no. 2 (February 2009): 632–39. https://doi.org/10.1161/STROKEAHA.108.530402.

PMID
19109539
Full Text

Wang, H., D. J. Christensen, M. P. Vitek, P. M. Sullivan, and D. T. Laskowitz. “APOE genotype affects outcome in a murine model of sepsis: implications for a new treatment strategy..” Anaesth Intensive Care 37, no. 1 (January 2009): 38–45. https://doi.org/10.1177/0310057X0903700111.

PMID
19157344
Full Text

Bour, Alexandra, Jeannette Grootendorst, Elise Vogel, Christian Kelche, Jean-Cosme Dodart, Kelly Bales, Pierre-Henri Moreau, Patrick M. Sullivan, and Chantal Mathis. “Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks..” Behav Brain Res 193, no. 2 (November 21, 2008): 174–82. https://doi.org/10.1016/j.bbr.2008.05.008.

PMID
18572260
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Sullivan, Patrick M., Brian E. Mace, Januario C. Estrada, Donald E. Schmechel, and Mark J. Alberts. “Human apolipoprotein E4 targeted replacement mice show increased prevalence of intracerebral hemorrhage associated with vascular amyloid deposition..” Journal of Stroke and Cerebrovascular Diseases : The Official Journal of National Stroke Association 17, no. 5 (September 2008): 303–11. https://doi.org/10.1016/j.jstrokecerebrovasdis.2008.03.011.

PMID
18755411
Full Text

Shelton, Shirley B., David B. Pettigrew, Alison D. Hermann, Weidong Zhou, Patrick M. Sullivan, Keith A. Crutcher, and Kenneth I. Strauss. “A simple, efficient tool for assessment of mice after unilateral cortex injury..” J Neurosci Methods 168, no. 2 (March 15, 2008): 431–42. https://doi.org/10.1016/j.jneumeth.2007.11.003.

PMID
18164073
Full Text

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