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Department of Pharmacology

Department of Pharmacology

Elva Diaz, Ph.D.

Elva Diaz, Ph.D.

Associate Professor
Ph.D.,
Stanford University
(530) 754-6080
e-mail

Recent/Current
Research Funding

National Institutes of Health

National Science Foundation

Graduate Group Affiliations

Biochemistry, Molecular, Cellular and Development Biology

Neuroscience

Pharmacology and Toxicology

Lab Page

Diaz Lab

Research Interests

Functional genomics of nervous system development:

My lab's main research interest is to understand molecular mechanisms of neural development using a rodent model system. In particular, my lab is interested in two areas: neural proliferation and synapse development. We used DNA microarrays as a tool to identify genes that are developmentally regulated during postnatal cerebellum development. We have identified several candidate molecules that increase in gene expression during the period of neural proliferation or synapse formation and we are currently studying the role of two molecules (Mad3 and synDIG1) in these processes.

Research Synopsis 

Mad3 and neural proliferation:

During development, Sonic hedgehog (Shh) regulates the proliferation of cerebellar granule neuron precursors (GNPs) in part via expression of Nmyc. My lab has demonstrated a novel role for the Myc/Max/Mad family member Mad3 in the Shh pathway to regulate Nmyc expression and cerebellar GNP proliferation. Mad3 mRNA is transiently expressed in GNPs during proliferation. Cultured GNPs express Mad3 in response to Shh stimulation in a cyclopamine-dependent manner. Mad3 is necessary for Shh-dependent GNP proliferation as measure by BrdU incorporation and Nmyc expression. Furthermore, overexpression of Mad3, but not other Mad proteins, is sufficient to induce GNP proliferation in the absence of Shh. Interestingly, cerebellar tumors and pre-tumor cells derived from patched (ptc) heterozygous mices express high levels of Mad3 compared with adjacent normal cerebellar tissue. These studies support a novel role for Mad3 in cerebellar GNP proliferation, and possibly tumorigenesis, and challenge the current paradigm that Mad3 should antagonize Nmyc by competition for direct DNA binding via Max dimerization. Our current research aims are: 1) to identify Mad3 target genes in GNPs and tumor cells using chromatin immunoprecipitation (ChIP) coupled to DNA microarrays (ChIP-on-chip); 2) to identify Mad3 interacting proteins using biochemical, genetic and proteomic approaches; and 3) to understand the role of Mad3 in tumor formation using in vivo mouse models.

SynDIG1 and synapse formation:

During development, synapse formation relies on signaling between pre- and postsynaptic neurons and the expression of specific genes. Synapse Differentiation Induced Gene (SynDIG1) was identified as a gene upregulated during synapse development whose upregulation failed in a mutant mouse line with defects in synaptic differentiation. We have shown that SynDIG1 encodes a novel, postsynaptic transmembrane protein that is a critical regulator of synapse development in cultured hippocampal neurons. Interestingly, SynDIG defines a family of four genes within the mouse genome that are expressed in distinct and partially overlapping cell types within nervous sytem tissues. Intriguingly, overexpression or knock-down of synDIG1 in cultured neurons alters the electrophysiological properties of excitatory synaptic transmission, presumably by the altered trafficking of AMPA receptors. Our current research aims are: 1) to characterize mice with a conditional deletion of the SynDIG1 gene; 2) to identify SynDIG1-interacting proteins; and 3) to test if SynDIG1 is subject to activity-dependent regulation at synapses.

Selected Publications

Kalashnikova E, Lorca RA, Kaur I, Barisone GA, Li BH, Ishimaru T, Trimmer JS, Mohapatra DP, and Díaz E. SynDIG1: an activity-regulated AMPA receptor interacting transmembrane protein that regulates excitatory synapse development, Neuron, 2010, 65: 80-93.

Díaz E (2010). Dynamic expression of SynDIG1 mRNA in cerebellar Purkinje neurons. Current Neurobiology, 1(1): 78-81.

Díaz E (2009), From microarrays to mechanisms of brain development and function [Invited review], Biochem Biophys Res Commun. 2009 Jul 24;385(2):129-31. Epub 2009 May 19.

Díaz E (2009), One decade later: What has gene expression profiling told us about neuronal cell types, brain function and disease? [Invited review]. Current Genomics, 10(5): 318-325.

Barisone GA, Yun JS, and Díaz E (2008), From cellellar proliferation to tumorigenesis: novel insights into the role of Mad3 [invited Extra-View], Cell Cycle, [invited Extra-View], Cell Cycle, 7: 423-7. Epub 2007 Dec 6.

Yun JS, Rust JM, Ishimaru T, and Díaz E (2007), A novel role for the Mad family member Mad3 in cerebellar granule neuron precursor proliferation, Mol. Cell. Biol. 27: 8178-8189.

Diaz E, Ge Y, Yang YH, Loh KC, Serafini TA, Okazaki Y, Hayashizaki Y, Speed TP, Ngai J and Scheiffele P. (2002). Molecular analysis of gene expression in the developing pontocerebellar projection system. Neuron 36, 417-434.

Diaz E, Yang YH, Ferreira T, Loh KC, Okazaki Y, Hayashizaki Y, Tessier-Lavigne M, Speed TP and Ngai J (2003). Analysis of gene expression in the developing mouse retina, Proc. Natl. Acad. Sci. USA 100, 5491-5496.

See: Complete List of Publications

Recent/Current Teaching

NSC 224A, Molecular and Deveopmental Neuroscience (Winter)

NSC 298 Topics in Molecular and Developmental Neurobiology Seminar (Winter, Spring)

PHA 250 Functional Genomics: From bench to bedside (Spring)

PHA 445 Integrative Medicine (Spring)

PHA 400B Neuropharmacology for Medical Students (Block 3)

Selected Honors and Awards

  • Helen Hay Whitney Fellowship
  • Alfred P. Sloan Research Fellowship
  • NIH Director's New Innovator Award