Concepcion Goldberg MD Lab Director

Our laboratory focuses on the molecular underpinnings of Alzheimer’s Disease. We focus on a protein called tau that is found normally in neurons. But when the tau protein aggregates or clumps into neurofibrillary tangles, it disrupts the integrity of the cells. This tau pathology is one of the classic hallmarks of Alzheimer's disease.

In another set of studies we are examining every protein found in the brain using a method based on cutting edge microarray technology. We are studying abnormal expression of proteins in tissue from people at high risk for AD and people with AD. We hope to identify novel brain chemicals that are involved in the pathological processes that result in neurodegenerative disease like AD and also protective factors. This will help us identify brain chemicals that can become treatment targets for new drugs.

Our current work involves gene expression profiling approaches to Alzheimer's disease and cellular models of neurodegeneration.  We have a collaboration with Terry Goldberg, PhD, also at the Center, on the study of post-mortem brain samples to look for regional differences in brain transcripts (i.e. brain chemicals) of people with genes that put them at risk for Alzheimer’s (apoE4 allele carriers) and other tissue from people who have no known genetic risk factors (non apoE4 allele carriers). These differences may help explain why people with this flavor of the apoE gene are at risk for late-onset Alzheimer’s. The post-mortem samples are from people who died of other causes, not Alzheimer’s, so we can isolate early changes in brain before disease.  We are also using microarray studies to look at expression of the tau protein and secondary effects due to the isoforms. In molecular experiments in living cells, we are examining the effects of abnormal tau on different cell functions, and how different drugs may impact tau protein. Tau fills the tangles in the Alzheimer’s brain and understanding how and why tau is involved with the disease can help solve the puzzle of the mind-robbing disease and lead to ways to prevent and treat Alzheimer’s.

Name:   Shufen Chen, MD Position:   Research Assistant Research:   Works with microarray technology in the study of the Molecular genetics of  Alzheimer's disease. Email:   schen3@nshs.edu

Selected Publications:

Conejero-Goldberg, C., Townsend, K., and Davies, P.  Effects of Cell Cycle Inhibitor Drugs on Tau Phosphorylation in N2aTau3R cells. Journal of Molecular Neuroscience, 35:143-150, 2008.

Conejero-Goldberg, C., Davies, P. and Ulloa, L. Alpha7 Nicotinic Acetylcholine Receptor: a Link Between Inflammation and Neurodegeneration. Neuroscience & Biobehavioral Reviews, 32:693-706, 2008.

Conejero-Goldberg, C.,  Wang, E., Yi, C., Goldberg,T.E., Jones-Brando, L.,  Marincola, F.M.,  Webster, M.J., and Torrey E.F. Infectious pathogen detection arrays: viral detection in cell lines and postmortem brain tissue. BioTechniques, 39:741-751, 2005.

Conejero-Goldberg, C., Torrey, E.F., and Yolken, R.H. Herpesviruses and Toxoplasma gondii in orbital frontal cortex of psychiatric patients. Schizophrenia Research, 60 (1):  65-69, 2003.

Ross, K.C., Waldman, B.C., Conejero-Goldberg, C., Freed, W. J. and Coleman, J.R. Transplantation of M213-2O cells with enhanced GAD67 expression into the inferior colliculus alters audiogenic seizures. Exp Neurol 177(1):338-40, 2002.

Truckenmiller, M. E., Vawter, M. P., Zhang, P., Conejero-Goldberg, C., Dillon-Carter, O., Morales, N., Cheadle, C., Becker, K.G. and Freed, W.J.: AF5, a CNS Cell Line Immortalized with an N-Terminal Fragment of SV40 Large T: Growth, Differentiation, Genetic Stability, and Gene Expression. Exp Neurol. 175(2):318-37, 2002.

Conejero-Goldberg, C., Tornatore, C., Abi-Saab, W., Monaco, M. C., Dillon-Carter, O., Vawter, M., Elsworth, J. and Freed, W. Transduction of Human GAD67 cDNA into Immortalized Striatal Cell Lines Using an Epstein Barr Virus-based Plasmid Vector Increases GABA Content. Experimental neurology, 161 (2): 453-461, 2000.

Conejero, C., Wright, R. and Freed, W.: Glutamate and antimitotic agents induce differentiation, p53 activation and apoptosis in rodent neostriatal cell lines immortalized with the tsA58 allele of SV40 large T antigen. Experimental neurology, 158: 109-120, 1999.

Dillon-Carter, O., Conejero, C., Tornatore, C., Poltorak, M. and Freed, W. : N18-RE-105 cells: differentiation and activation of p53 in response to glutamate and adriamycin is blocked by SV40 large T antigen tsA58. Cell Tissue Res., 291: 191-205, 1998.

Conejero, C.:  Anion exchanger AE1 as a candidate pathway for taurine transport in rat erythrocytes.  Am. J. Physiol.: Cell Physiol., 272: C1457-C1464, 1997.

Martin del Rio, R., Galarreta, M., Menendez, N., Conejero, C. and Solis, J.M.: Taurine is a substrate of the anion exchanger transport systems. Taurine 2, edited by Huxtable et al. Plenum Press, New York, 1996.

Moore, K.D., Dillon-Carter, O., Conejero, C., Poltorak, M., Chedid, M., Tornatore, C. and Freed, W.:  In vitro properties of a newly established medulloblastoma cell line, MCD-1.  Mol. Chem. Neuropathol., 29: 107-126, 1996.

Galarreta, M., Solís, J.M., Menéndez, N., Conejero, C. and Martín del Río, R.:  Nicotinamide adenine dinucleotides mimic adenosine inhibition on synaptic transmission by decreasing glutamate release in rat hippocampal slices.  Neurosci. Lett. 159:55-58, 1993.

Menéndez, N., Solís, J.M., Herreras, O., Galarreta, M., Conejero, C. and Martín del Río, R.:  Taurine release evoked by NMDA receptor activation is largely dependent on calcium mobilization from intracellular stores. Eur. J. Neuroscience 5:1273-1279, 1993.