Sanders-Brown Faculty

Peter T. Nelson, M.D.,Ph.D.

Associate Professor

Departmental Affiliation(s):

Pathology, Division of Neuropathology

Research Focus:

Non-coding RNA in neurodegenerative disease

In the lab:

Dr. Wang-Xia Wang

Dr. Bernard R. Wilfred

Ms. Willa Huang

James Dimayuga

Mary Jennings

Kevin Xie

 

 

Kevin and Mary - students in the lab

 

 

 

 

Work on RNA biology may help point toward strategies to 'un-tangle' the biological questions of Alzheimer's disease, such as why neuritic plaques and neurofibrillary tangles develop in the brains of Alzheimer's patients. (lower left figure shows a low-power photomicrograph depicting miRNA in situ hybridization from human hippocampus; and, at lower right, a medium-power photomicrograph shows human brain stained with a silver impregnation technique to highlight the abnormal and unhealthy-appearing brain microenvironment).

 

 

Research Interests:

Dr. Nelson is an experimental neuropathologist whose research focuses upon the molecular neurochemistry of the human brain —in health and in neurodegenerative disease —particularly in the context of RNA biology. The study of small regulatory RNAs is a relatively new and unexplored research field with much potential. Dr. Nelson's work has focused upon the predominant small regulatory RNA subtype in humans (and in all animals), which are termed microRNAs (miRNAs). MiRNAs subserve fundamental biological functions in all animals studied. He invented new techniques to analyze and manipulate these small molecules, and studies how miRNA biology is altered in neurodegenerative diseases. Dr. Nelson seeks both to understand how miRNAs contribute to disease pathogenesis, and to explore how specially-designed RNAs may be applied for therapeutic strategies.

 

Recent Publications:

Nelson PT, Jicha GA, Kryscio RJ, Abner EL, Schmitt FA, Cooper, G, Xu, LO, Smith CD, Patel E, Markesbery WR.  Low sensitivity in clinical diagnoses of dementia with Lewy bodies.  J. Neurology, In Press.

Nelson PT, Schmitt FA, Jicha GA, Kryscio RJ, Abner EL, Cooper, G, Xu, LO, Smith CD, Patel E, Markesbery WR.  Relative preservation of MMSE scores in autopsy-proven dementia with Lewy bodies.  Neurology, In Press.

Berger JR, Fee DB, Nelson P, Nuovo G.  Coxsackie B meningoencephalitis in a patient with acquired immunodeficiency syndrome and a multiple sclerosis-like illness.  J Neurovirol. 2009 May 14:1-6.

Berger JR, Dillon DA, Young BA, Goldstein SJ, Nelson P.  Cystinosis of the brain and spinal cord with associated vasculopathy.  J Neurol Sci. 2009 Sep 15;284(1-2):182-5.

Nelson PT, Abner EL, Schmitt FA, Kryscio RJ, Jicha GA, Santacruz K, Smith CD, Patel E, Markesbery WR.  Brains With Medial Temporal Lobe Neurofibrillary Tangles But No Neuritic Amyloid Plaques Are a Diagnostic Dilemma But May Have Pathogenetic Aspects Distinct From Alzheimer Disease.   J Neuropathol Exp Neurol. 2009 [In press]

Nelson PT, Wilfred BR. In situ hybridization is a necessary experimental complement to microRNA (miRNA) expression profiling in the human brain.  Neurosci Lett. 2009 Apr 23. [In press]

Nelson PT, Kryscio RJ, Abner EL, Schmitt FA, Jicha GA, Mendiondo MS, Cooper G, Smith CB, Markesbery WR.  Acetylcholinesterase inhibitor treatment is associated with relatively slow cognitive decline in patients with Alzheimer's disease and AD + DLB.  J Alzheimers Dis. 2009 Jan;16(1):29-34.

Nelson PT, Braak H, Markesbery WR.  Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship.  J Neuropathol Exp Neurol. 2009 Jan;68(1):1-14.

Jicha GA, Schmitt FA, Abner E, Nelson PT, Cooper GE, Smith CD, Markesbery WR.  Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease.  Neurobiol Aging. 2008 Nov 19.

Nelson PT, Abner, EA, Scheff, SW, Schmitt, FA, Kryscio, RJ, Jicha, GA, Smith, CD, Patel, E, Markesbery, WR, Alzheimer pathology in the precuneus is not increased relative to other areas of neocortex across a range of cognitive impairment.  Neurosci Letters (In Press).

Nelson PT, Abner, EA, Schmitt, FA, Kryscio, RJ, Jicha, GA, Smith, CD, Davis, DG, Poduska, JW, Patel, E, Mendiondo, MS, Markesbery, WR, Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons, Brain Pathol, (In Press).

Jicha, GA, Schmitt, FA, Abner, EL, Nelson, PT, Cooper, GE, Smith, CD, and Markesbery, WR, Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease.  Neurobiol Aging, 2008 (In Press)

Nelson PT, Smith, CD, Abner, EA, Schmitt, FA, Scheff, SW, Davis, GD, Keller, JN, Jicha, GA, Davis, D, Wang, W-X, Hartman, A, Katz, DG, and Markesbery WR, Human cerebral neuropathology of Type 2 diabetes mellitus.  BBA-Mol Basis of Disease, 2008 (In Press)

Nelson PT*, Wang WX, Wilfred BR, Tang G.  Technical variables in high-throughput miRNA expression profiling: Much work remains to be done.  Biochim Biophys Acta. 2008 Apr 7.

Cuellar TL, Davis TH, Nelson PT, Loeb GB, Harfe BD, Ullian E, McManus MT.  Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration.  Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5614-9.

Wang WX, Wilfred BR, Baldwin DA, Isett RB, Ren N, Stromberg A, Nelson PT.  Focus on RNA isolation: Obtaining RNA for microRNA (miRNA) expression profiling analyses of neural tissue.  Biochim Biophys Acta. 2008 Feb 13.

Wang, W-X, Nelson PT, and Tang, G, RNA interference and miRNA pathways: mechanisms and protein machinery.  Wiley Encyclopedia of Chemical Biology.  2008

 Wang W-X, Rajeev, BW, Stromberg AJ, Ren N, Tang G, Huang Q, Rigoutsos I, and Nelson PT.  The expression of microRNA miR-107 decreases early in Alzheimer’s disease and may accelerate disease progression through regulation of BACE1.  J Neuroscience 2008 28(5): 1213-23.

Nelson PT, Wang, W-X, and Rajeev, BW.  MicroRNAs in neurodegeneration.  Brain Pathology 2008 18(1): 130-8.

Nelson PT, Jicha, GA, Schmitt, FA, Liue, H, Davis, DG, Mendiondo, MS, Abner, EL, and Markesbery, WR, Clinicopathological correlations in a large Alzheimer Disease Center autopsy cohort: neuritic plaques and neurofibrillary tangles "do count" when staging disease severity. J Neuropathol Exp Neurol. 2007 Dec; 66(12): 1136-1146.

Nelson PT, De Planell-Saguer M, Lamprinaki S, Kiriakidou M, Zhang P, O'Doherty U, Mourelatos Z. A novel monoclonal antibody against human Argonaute proteins reveals unexpected characteristics of miRNAs in human blood cells. RNA. 2007 Oct;13(10):1787-92.

Nelson PT, Keller JN.  RNA in brain disease: no longer just "the messenger in the middle". J Neuropathol Exp Neurol. 2007 Jun;66(6):461-8.

Kiriakidou M, Tan GS, Lamprinaki S, De Planell-Saguer M, Nelson PT, Mourelatos Z. An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell. 2007 Jun 15;129(6):1141-51.

Wilfred BR, Wang WX, Nelson PT.  Energizing miRNA research: a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways.  Mol Genet Metab. 2007 Jul;91(3):209-17.

Nelson PT, Zhang PJ, Spagnoli GC, Tomaszewski JE, Pasha TL, Frosina D, Caballero OL, Simpson AJ, Old LJ, Jungbluth AA.  Cancer/testis (CT) antigens are expressed in fetal ovary.  Cancer Immun. 2007 Jan 12;7:1.