Eric Blalock, Ph.D.

Assistant Professor,
University of Kentucky, 1997.

Office: MS-310, Chandler Medical Center (0298)
Tel: (859) 323-8033

Research Interests

We are interested in the processes that lead to age, and age-related neurodegenerative changes (e.g., Alzheimer's disease) in the hippocampus, and how these changes affect memory and cognition. In addition, our laboratory, in collaboration with others, studies the effects of stress, estrogen, sleep deprivation, and epileptiform activity on the hippocampal formation using electrophysiologic, behavioral, and molecular techniques.

One difficulty in dovetailing molecular and electrophysiological approaches has been the heterogeneity of brain tissue. Whole brain is made up of several different cell types, roughly classified as neuronal, glial, and vascular. Thus, approaches that examine whole tissue, when compared to approaches that examine only the neuronal components of that tissue (e.g., molecular vs electrophysiologic), must be interpreted with caution.

To more closely align these different assessments of hippocampal function, we have employed the partially dissociated "zipper" slice preparation, which permits the extraction of intact single neurons (with extensive neuritic arbors), for molecular analysis. While this preparation provides a relatively homogenous sample for neuronal gene expression (i.e., the same cell used for both electrophysiological and molecular characterization), it does have clear limitations. For instance, only a few genes can be measured simultaneously with quantitative Real Time PCR, and the mRNA must be carefully amplified.

We are working closely with Dr. Kuey-Chu Chen's laboratory and the microarray core facility regarding these procedures. In collaboration, we have published work demonstrating significant positive correlations between L-type voltage-gated Ca2+ channel activity and the mRNA level of the alpha 1D subunit of that channel in hippocampal cells (Chen et al., 2001; Blalock et al., 2001). Further, Dr. Chen is also developing amplification strategies that allow the examination of single neuron global gene expression with microarrays.

Finally, using powerful new microarray technology (which allows the simultaneous measurement of thousands of genes) we are testing for patterns of change across the transcriptome in subregions of the hippocampus using various treatments (Blalock et al., 2003 & 2004). In the course of these microarray studies, it has become evident that new data analysis methods are necessary. To that end, we are also developing bioinformatic tools (StatiGen zip archive) that assign genes to patterns of change using statistical methodologies. Further, with these tools we hope to provide automated assessments of the probability that such patterns (and the genes of which they are comprised) could have been detected by chance alone.

Selected Publications

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Hulshizer R, Blalock EM (2007)
Post hoc pattern matching: assigning significance to statistically defined expression patterns in single channel microarray data. BMC Bioinformatics 8:240.

Landfield PW, Blalock EM, Chen KC, Porter NM (2007)
A New Glucocorticoid Hypothesis of Brain Aging: Implications for Alzheimer's Disease.
Current Alzheimer's Research 4: 205-212

Rowe* WB, Blalock* EM, Chen KC, Kadish I, Wang D, Barrett JE, Thibault O, Porter NM, Rose GM, Landfield PW (2007)
Hippocampal Expression Analyses Reveal Selective Association of Immediate-Early, Neuroenergetic, and Myelinogenic Pathways with Cognitive Impairment in Aged Rats.
J Neurosci 27: 3098-3110

Norris CM^*, Blalock EM^*, Thibault O, Brewer LD, Clodfelter GV, Porter NM, Landfield PW (2006)
Electrophysiological Mechanisms of Delayed Excitotoxicity: Positive Feedback Loop Between NMDA Receptor Current and Depolarization-Mediated Glutamate Release. J Neurophys 96: 2488-2500.
^*authors contributed equally

Kelly KM, Nadon NL, Morrison JH, Thibault O, Barnes CA, Blalock EM (2005)
"The neurobiology of aging" Epilepsy Res. 67:1-16.

Blalock EM, Chen KC , Stromberg AJ, Norris CM, Kadish I, Kraner SD, Porter NM, Landfield PW (2005)
"Harnessing the Power of Gene Microarrays for the Study of Brain Aging and Alzheimer's Disease: Statistical Reliability and Functional Correlation" Aging Research Reviews 4: 481-512.

Norris CM, Kadish I, Blalock EM, Chen KC, Thibault V, Porter NM, Landfield PW, Kraner SD (2005)
Calcineurin triggers reactive/inflammatory processes in astrocytes and is upregulated in aging and Alzheimer's models. J Neurosci. 25:4649-4658.

Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW (2004)
Incipient Alzheimer's disease: Microarray correlation analyses reveal major transcriptional and tumor suppressor responses. PNAS 101:2174-2178.

Blalock, EM (ed.) (2003)
"A Beginner's Guide to Microarrays" Kluwer Academic Publishers, New York (347 pages)

Blalock EM, Chen KC, Sharrow K, Herman JP, Porter NM, Foster TC, Landfield PW. (2003)
Gene microarrays in hippocampal aging: statistical profiling identifies novel processes correlated with cognitive impairment. J Neurosci. 23:3807-3819.

Peng X, Wood CL, Blalock EM, Chen KC, Landfield PW, Stromberg AJ. (2003)
Statistical implications of pooling RNA samples for microarray experiments. BMC Bioinformatics. 4:26.

Norris CM, Blalock EM, Chen KC, Porter NM, Landfield PW. (2002)
Calcineurin enhances L-type Ca(2+) channel activity in hippocampal neurons: increased effect with age in culture. Neuroscience.110:213-225.

Blalock EM, Chen KC, Vanaman TC, Landfield PW, Slevin JT. (2001)
Epilepsy-induced decrease of L-type Ca2+ channel activity and coordinate regulation of subunit mRNA in single neurons of rat hippocampal 'zipper' slices. Epilepsy Res. 43:211-226.

Chen K-C, Blalock EM, Thibault O, Kaminker P and Landfield PW. (2001)
Expression of alpha 1D subunit mRNA is correlated with L-type Ca2+ channel activity in single neurons of hippocampal "zipper" slices. PNAS 97(8):4357-4362.

Blalock EM, Porter NM, Landfield PW. (1999)
Decreased G-protein-mediated regulation and shift in calcium channel types with age in hippocampal cultures. J Neurosci 19:8674-84.

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