John Cave, Ph.D.

Ph.D., University of California at Berkeley 
A.B., Kenyon College

Cave JW, Baker H (In press) Adult Neurogenesis in the SVZ and Migration to the Olfactory Bulb. In Handbook of Olfaction and Gustation. R Doty (Ed). New York, NY: Marcel Dekker.

Banerjee K, Akiba Y, Baker H, Cave JW (2013) Epigenetic control of neurotransmitter expression in olfactory bulb interneurons. Int J Dev Neurosci.(In press). PMID: 23220178

Cave JW, Banerjee K, Baker H (2012) Species-specific molecular mechanisms establishing the dopamine neuronal phenotype. In Dopamine: Functions, Regulation and Health Effects. E Kudo & Y Fujii (Eds).Happauge, NY: Nova Science Publishers. 

Cave JW (2011) Selective repression of Notch pathway target gene transcription. Dev Biol 1:123-31.

Cave JW, Li X, Caudy MA (2011) Differential transcriptional regulation through distinct suppressor of hairless DNA binding site architectures in proneural clusters during notch signaling. Mol Cell Biol 31:22-9. PMID: 21041480

Cave JW, Akiba Y, Banerjee K, Berlin RA, Baker H (2010) Differential regulation ofdopaminergic gene expression by Er81. J Neurosci 30:4717-24. PMID: 20357122

Akiba Y, Cave JW, Akiba N, Langley B, Ratan RR, Baker H (2010) Histone deacetylase activity represses tyrosine hydroxylase expression in olfactory bulb interneuron progenitors. Biochem Biophys Res Comm 393:673-7. PMID: 20170631 

Cave JW, Baker H (2009) Dopamine systems in the forebrain. Adv Exp Med Biol 651:15-35. PMID: 19731547

Cave JW, Li X, Caudy MA (2009) The daughterless N-terminus directly mediates synergistic interactions with notch transcription complexes via the SPS+A DNA transcription code. BMC Res Notes 2:65. PMID: 19400956

Akiba N, Jo S, Akiba Y, Baker H, Cave JW (2009) Expression of EGR-1 in a subset of olfactory bulb dopaminergic cells. J Mol Histology 40:151-5. PMID: 19387849 

Akiba Y, Saski H, Baker H, Estevez A, Cave JW (2009) GABA-mediated regulation of the activity-dependent olfactory bulb dopaminergic phenotype. J Neurosci Res 87:2211-21. PMID: 19301430

Cave JW, Caudy MA (2008) Promoter-specific co-activation by mastermind. Biochem Biophys Res Comm 377:658-661. PMID: 18930034

Saino-Saito S, Cave JW, Akiba Y, Sasaki H, Goto K, Kobayashi K, Berlin RA, Baker H (2007) ER81 and CaMKIV identify anatomically and phenotypically defined subsets of olfactory bulb interneurons. J Comp Neurol 502:485-496. PMID: 17394138 

Cave JW, Loh F, Surpris JW, Xia L, Caudy MA (2005) A DNA transcription code for cell-specific gene activation by notch signaling. Current Biology 15:94-104. PMID: 15668164

Cave JW, Cho HS, Batchelder AM, Yokota H, Kim R, Wemmer DE (2001) Solution nuclear magneticresonance structure of a protein disulfide oxidoreductase from methanococcus jannaschii. Protein Science 10:384-396. PMID: 11266624 

Cave JW, Kremer W, Wemmer DE (2001) Backbone dynamics of sequence specific recognition and binding by the yeast Pho4 bHLH domain probed by NMR. ProteinScience 9:2354-2365. PMID: 11206057

Differentiation of the olfactory bulb dopaminergic phenotype
This project focuses on the mechanisms regulating transcription of the tyrosine hydroxylase (Th) and glutamic acid decarboxylase1 (Gad1) genes, which encode the rate-limiting enzymes for biosynthesis dopamine and GABA neurotransmitters, respectively. Both of these enzymes are co-expressed in all dopaminergic interneurons of the olfactory bulb and our laboratory has identified several potentially novel cis-regulatory regions that control the transcription of these genes. We are presently testing the functionality of these novel regions as well as establishing the specific transcription factors that bind to them in order to define the mechanisms by which Th and Gad1 transcription is regulated. This work will provide an unprecedented molecular understanding in the specification of dopaminergic and GABAergic neurotransmitter phenotypes from neural stem cells in the sub-ventricular zone.

Regulation of adult neural stem cell proliferation and differentiation by microRNA
In collaboration with Tao Sun’s Laboratory (Weill Cornell Medical College), this project examines novel regulation of neural stem cell proliferation and differentiation by microRNA in the adult subventricular zone. These studies will establish both the specific target genes for these microRNA and whether these microRNA regulate the differentiation of a specific subset of olfactory bulb interneurons.

 Specification of neuronal phenotypes by transcription factor expression
Neural stem cells within the adult subventricular zone are heterogeneous and producedifferent subsets of olfactory bulb interneuron phenotypes. Many of these phenotypic subsets are defined by the expression of specific transcription factors. The goal of this project is to establish the molecular mechanisms by which these transcription factors specify distinct neuronal fates. We are particularly interested in the unique roles performed by the Er81 (Etv1), Pax6 and Foxp2 proteins. We seek to identify the target genes directly regulated by these transcription factors as well as understand how the expression of transcription factors are differentially controlled in subventricular zone neural stem cells. We are also interested in understanding how the function of these transcription factors compare to the roles they also have in the development of other brains regions, such as the cortex and cerebellum.

 Human olfactory bulb
Throughout the entire life of the animal, studies in rodents indicate that olfactory bulb interneurons continuously turnover and are replaced by interneurons generated by the neural stem cells in the subventricular zone. In humans, however, the extent to which new interneurons generated in the subventricular zone integrate into the adult olfactory bulb is controversial. Our laboratory is interested in establishing whether the relative proportions of specific neuron phenotypes in the human olfactory bulb change through out life and how specific olfactory bulb neuronal populations are affected by aging-related diseases, such as Parkinson’s Disease. Because nearly all cases of sporadic Parkinson’s Disease are associated with an impaired sense of smell many years before the motor symptoms are detected, we are particularly interested in establishing whether there is a select population of olfactory bulb neurons that are sensitive to Parkinson-mediated neurodegeneration. Such an identification would provide novel insight into the etiology of diseaseas well as open new routes to develop novel biomarkers that could greatly advance our ability to identify those at-risk of developing the disease. 

Harriet Baker, Weill Cornell Medical College/Burke Medical Research Institute

NIH R01 DC008955 (6/11-5/16) Plasticity in the Aging Olfactory System