Robert George Nagele, PhD
Science Center 313A
Rutgers University, New Brunswick, NJ, PhD, 1980
Our research is focused on two areas. The first emerged from our recent discovery that all human blood contains thousands of autoantibodies which appear to play a role in the clearance of cell and tissue debris generated by the body on a day-to-day basis. We have further shown that this is conserved among all mammals and that ongoing disease leads to an increased production of debris from the organ/tissue affected. This surge of debris enters the blood and subsequently stimulates the immune system to selectively increase the production of autoantibodies that clear this disease-specific debris. We have used human protein microarray technology to detect and identify disease-specific autoantibodies which can now be used as biomarkers to confirm the presence of disease. Thus far, we have thus successfully employed disease-specific autoantibodies as biomarkers to diagnose Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and early-stage breast cancer in human subjects using a single drop of blood. Diagnostic accuracies for each of these diseases exceeds 95% using our analytical strategy. This work was seed-funded by the Foundation Venture Capital Group, and subsequent efforts have led to the establishment of two start-up companies (Durin Technologies, Inc. and Beren Technologies, Inc). The Alzheimer’s diagnostic work is currently funded by a grant from the Osteopathic Heritage Foundation; the Parkinson’s disease studies by the Michael J Fox Foundation. In the future, our new Biomarker Discovery Center, created within the New Jersey Institute for Successful Aging, will spearhead these efforts as well as our new efforts towards diagnosing the effects of traumatic brain injury, where we believe that our diagnostic strategy will be able to detect the presence of neurodegenerative changes in the brain resulting from repeated trauma. We are presently seeking industrial partners to accelerate work on the development of diagnostic test kits for a number of diseases that would lead to eventual FDA approval. A number of patents have been filed with UMDNJ. Our second research focus is to elucidate cellular and molecular mechanisms of Alzheimer’s disease. Most recently, this work has led us to conclude that breakdown of the blood-brain barrier is a requisite early trigger for a number of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. In view of this, we are now investigating factors and conditions that lead to blood-brain barrier breakdown and are utilizing in vitro model systems to screen for drugs that can block this from happening in blood vessels throughout the brain. This work has already led to a patent for the use of darapladib, an inhibitor of atherosclerosis, for the treatment of all neurodegenerative diseases in collaboration with GlaxoSmithKline. This drug is currently in clinical trial for treatment of atherosclerosis. Other drugs are currently being tested for their ability to block blood-brain barrier breakdown.
(Updated May 2016)
- Wu H, Brown EV, Acharya NK, Appelt DM, Marks A, Nagele RG, Venkataraman V. Age-dependent increase of blood-brain barrier permeability and neuron-binding autoantibodies in S100B knockout mice. Brain Res, 1637: 154-67, April 2016.
- Sedeyn JC, Wu H, Hobbs RD, Levin EC, Nagele RG, Venkataraman V. Histamine Induces Alzheimer's Disease-Like Blood Brain Barrier Breach and Local Cellular Responses in Mouse Brain Organotypic Cultures. Biomed Res Int, 937148: 1-12, November 2015.
- DeMarshall CA, Han M, Nagele EP, Sarkar A, Acharya NK, Godsey G, Goldwaser EL, Kosciuk M, Thayasivam U, Belinka B, Nagele RG; Parkinson’s Study Group Investigators. Potential utility of autoantibodies as blood-based biomarkers for early detection and diagnosis of Parkinson's disease. Immunol Lett, 168(1): 80-8, November 2015.
- DeMarshall C, Sarkar A, Nagele EP, Goldwaser E, Godsey G, Acharya NK, Nagele RG. Utility of autoantibodies as biomarkers for diagnosis and staging of neurodegenerative diseases. Int Rev Neurobiol, 122: 1-51, June 2015.
- Acharya NK, Goldwaser EL, Forsberg MM, Godsey GA, Johnson CA, Sarkar A, DeMarshall C, Kosciuk MC, Dash JM, Hale CP, Leonard DM, Appelt DM, Nagele RG. Sevoflurane and Isoflurane induce structural changes in brain vascular endothelial cells and increase blood-brain barrier permeability: Possible link to postoperative delirium and cognitive decline. Brain Res, 1620: 29-41, September 2015.
- Chu HP, Liao Y, Novak JS, Hu Z, Merkin JJ, Shymkiv Y, Braeckman BP, Dorovkov MV, Nguyen A, Clifford PM, Nagele RG, Harrison DE, Ellis RE, Ryazanov AG. Germline quality control: eEF2K stands guard to eliminate defective oocytes. Dev Cell, 28(5): 561-72 , March 2014.
- Acharya NK, Nagele EP, Han M, Nagele RG. Autoantibodies: double agents in human disease.
Sci Transl Med, 5(186): 186fs19, May 2013.
- Nagele EP, Han M, Acharya NK, DeMarshall C, Kosciuk MC and Nagele RG. Natural IgG autoantibodies are abundant and ubiquitous in human sera, and their number is influenced by age, gender, and disease. PLoS ONE, 8(4): e660726, Apr 2013.
- Acharya, NK, Levin EC, Clifford PM, Han M, Tourtellotte R, Chamberlain D, Pollaro M, Coretti NJ, Kosciuk MC, Nagele EP, Demarshall C, Freeman T, Guan C, Shi Y, Wilensky RL, Macphee CH, Nagele RG. Diabetes and hypercholesterolemia increase blood-brain barrier permeability and brain amyloid deposition: beneficial effects of the LpPLA2 inhibitor darapladib. J Alzheimers Dis, 35(1): 179-98, Jan 2013.
- Ochoa-Alvarez JA, Krishnan H, Shen Y, Acharya NK, Han M, McNulty DE, Hasegawa H, Hyodo T, Senga T, Geng JG, Kosciuk M, Shin SS, Goydos JS, Temiakov D, Nagele RG, Goldberg GS. Plant lectin can target receptors containing sialic acid, exemplified by podoplanin, to inhibit transformed cell growth and migration. PLoS One, 7(7): e41845, 2012.
- Acharya NK, Nagele EP, Han M, Coretti NJ, DeMarshall C, Kosciuk MC,Nagele RG. Neuronal PAD4 expression and protein citrullination: possible role in production of autoantibodies associated with neurodegenerative disease. J Autoimmun, 38(4): 369-80, Jun 2012.
- Han M, Nagele E, DeMarshall C, Acharya N, Nagele R. Diagnosis of Parkinson's disease based on disease-specific autoantibody profiles in human sera. PLoS One, 7(2): e32383, 2012.
- Bakshi K, Kosciuk M, Nagele RG, Friedman E, Wang HY. Prenatal cocaine exposure increases synaptic localization of a neuronal RasGEF, GRASP-1 via hyperphosphorylation of AMPAR anchoring protein, GRIP. PLoS One, 6(9): e25019, 2011.
- Nagele E, Han M, DeMarshall C, Belinka B, Nagele R. Diagnosis of Alzheimer's disease based on disease-specific autoantibody profiles in human sera. PLoS One, 6(8): e23112, 2011.
- Nagele RG, Clifford PM, Siu G, Levin EC, Acharya NK, Han M, Kosciuk MC, Venkataraman V, Zavareh S, Zarrabi S, Kinsler K, Patel N, Nagele EP, Dash J, Wang HY, Levitas A. Brain-reactive autoantibodies prevalent in human sera increase intraneuronal amyloid-β1-42 deposition. J Alzheimers Dis, 25: 605-622, Mar 2011.
- Levin EC, Acharya NK, Han M, Zavareh SB, Sedeyn JC, Venkataraman V, Nagele RG. Brain-reactive autoantibodies are nearly ubiquitous in human sera and may be linked to pathology in the context of blood-brain barrier breakdown. Brain Res, 1345(23): 221-32, Jul 2010.
- Levin EC, Acharya NK, Sedeyn JC, Venkataraman V, Wang HY, D'Andrea MR, Nagele RG. Neurons expression of vimentin in the Alzheimer's disease brain may be part of a generalized dendritic damage-response mechanism. Brain Res, 1298: 194-207, Nov 2009.
- Bakshi K, Gennaro S, Chan CY, Kosciuk M, Liu J, Stucky A,Trenkner E, Friedman E, Nagele RG, Wang HY. Prenatal cocaine reduces AMPA receptor synaptic expression through hyperphosphorylation of the synaptic anchoring protein GRIP. J Neurosci, 29(19): 6308-19, May 2009.
- Clifford PM, Zarrabi S, Siu G, Kinsler KJ, Kosciuk MC, Venkataraman V, D'Andrea MR, Dinsmore S, Nagele RG. Abeta peptides can enter the brain through a defective blood-brain barrier and bind selectively to neurons. Brain Res, 1 142: 223-36, Apr 2007.
- Siu, G, P Clifford, M Kosciuk, V Venkataraman and RG Nagele. Glial cells and Abeta peptides in Alzheimer’s disease pathogenesis. In: Abeta Peptides and Alzheimer’s Disease, ed. Colin Barrow and David H Small, Springer-Verlag, pp. 216-233, 2006.
- D’Andrea MR, Nagele RG. Targeting the alpha 7 nicotinic acetylcholine receptor to reduce amyloid accumulation in Alzheimer's disease pyramidal neurons. Curr Pharm Des, 12(6): 677-84, 2006.
- Nagele RG, Wegiel J, Venkataraman V, Imaki H, Wang KC, Wegiel J. Contribution of glial cells to the development of amyloid plaques in Alzheimer's disease. Neurobiol Aging, 25(5): 663-74, May 2004.
- Nagele RG, D'Andrea MR, Lee H, Venkataraman V, Wang HY. Astrocytes accumulate A beta 42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains. Brain Res, 971(2): 197-209, May 2003.
- D’Andrea MR, Nagele RG, Wang HY, Lee DHS. Consistent immunohistochemical detection of intracellular beta-amyloid42 in pyramidal neurons of Alzheimer’s disease entorhinal cortex. Neurosci Lett, 333(3): 163-6, Nov 2003.
- Nagele, RG, D’Andrea MR, Lee DHS, Wang H. Intracellular accumulation of beta-amyloid(1-42) in neurons is facilitated by the alpha 7 nicotinic acetylcholine receptor in Alzheimer’s disease. Neuroscience, 110(2): 199-211, 2002.
- Wang, H-Y, MR D’Andrea and RG Nagele. Cerebellar diffuse amyloid plaques are derived from dendritic AB42 accumulations in Purkinje cells. Neurobiol Aging, 23(2): 213-23, Mar-Apr 2002.
- Venkataraman V, Nagele RG. Calcium-sensitive ROS-GC1 signaling outside of photoreceptors: a common theme. Mol Cell Biochem, 230(1-2): 117-24, Jan 2002.
Webpage Updated May 2013