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

Becchis, M., P. M. Sullivan, P. Ordronneau, P. Petrusz, and D. R. Joseph. “Distribution of immunoreactive androgen-binding protein/sex hormone-binding globulin in tissues of the fetal rat..” Steroids 61, no. 7 (July 1996): 392–400. https://doi.org/10.1016/0039-128x(96)00049-9.

PMID
8837290
Full Text

Xu, P. T., D. Schmechel, T. Rothrock-Christian, D. S. Burkhart, H. L. Qiu, B. Popko, P. Sullivan, et al. “Human apolipoprotein E2, E3, and E4 isoform-specific transgenic mice: human-like pattern of glial and neuronal immunoreactivity in central nervous system not observed in wild-type mice..” Neurobiology of Disease 3, no. 3 (January 1996): 229–45. https://doi.org/10.1006/nbdi.1996.0023.

PMID
8980023
Full Text

Joseph, D. R., D. R. Wang Yan Min, and P. M. Sullivan. “Characterization and sex steroid hormone regulation of multiple alternate androgen-binding protein/sex hormone-binding globulin RNA transcripts in rat brain.” Endocrine 2, no. 8 (January 1, 1994): 749–58.

Scholars@Duke

Reventos, J., P. M. Sullivan, D. R. Joseph, and J. W. Gordon. “Tissue-specific expression of the rat androgen-binding protein/sex hormone-binding globulin gene in transgenic mice..” Molecular and Cellular Endocrinology 96, no. 1–2 (October 1993): 69–73. https://doi.org/10.1016/0303-7207(93)90096-3.

PMID
8276140
Full Text

Sullivan, P. M., Y. M. Wang, and D. R. Joseph. “Identification of an alternate promoter in the rat androgen-binding protein/sex hormone-binding globulin gene that regulates synthesis of a messenger RNA encoding a protein with altered function..” Molecular Endocrinology (Baltimore, Md.) 7, no. 5 (May 1993): 702–15. https://doi.org/10.1210/mend.7.5.7686253.

PMID
7686253
Full Text

Joseph, D. R., P. M. Sullivan, Y. M. Wang, D. E. Millhorn, and D. M. Bayliss. “Complex structure and regulation of the ABP/SHBG gene..” The Journal of Steroid Biochemistry and Molecular Biology 40, no. 4–6 (January 1991): 771–75. https://doi.org/10.1016/0960-0760(91)90302-l.

PMID
1958575
Full Text

Sullivan, P. M., P. Petrusz, C. Szpirer, and D. R. Joseph. “Alternative processing of androgen-binding protein RNA transcripts in fetal rat liver. Identification of a transcript formed by trans splicing..” The Journal of Biological Chemistry 266, no. 1 (January 1991): 143–54.

PMID
1702422
Scholars@Duke

Joseph, D. R., P. M. Sullivan, Y. M. Wang, C. Kozak, D. A. Fenstermacher, M. E. Behrendsen, and C. A. Zahnow. “Characterization and expression of the complementary DNA encoding rat histidine decarboxylase..” Proceedings of the National Academy of Sciences of the United States of America 87, no. 2 (January 1990): 733–37. https://doi.org/10.1073/pnas.87.2.733.

PMID
2300558
Full Text

Wang, Y. M., P. M. Sullivan, P. Petrusz, W. Yarbrough, and D. R. Joseph. “The androgen-binding protein gene is expressed in CD1 mouse testis..” Mol Cell Endocrinol 63, no. 1–2 (May 1989): 85–92.

PMID
2753230
Scholars@Duke

Lubahn, D. B., D. R. Joseph, P. M. Sullivan, H. F. Willard, F. S. French, and E. M. Wilson. “Cloning of human androgen receptor complementary DNA and localization to the X chromosome..” Science 240, no. 4850 (April 15, 1988): 327–30.

PMID
3353727
Scholars@Duke

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