Graduate Studies Faculty
Curtis A. Machida, Ph.D.
Programs:Biochemistry & Molecular Biology
Research Interests:beta-adrenergic receptor transcriptional and post-transcriptional regulatory mechanisms, bZIP transcription factors, nuclear LIM interactor - interaction factors, microbiological determinants of caries risk, viral vectors for gene therapy and transduction into stem cells; medical » PubMed Listing
Preceptor RotationsDr. Machida has not indicated availability for preceptor rotations at this time.
Faculty MentorshipDr. Machida has not indicated availability as a mentor at this time.
Curtis Machida obtained an A.B. degree from the University of California at Berkeley in 1976, and a Ph.D. degree in Microbiology from the Oregon Health & Science University (OHSU) in 1982. Over the next six years, he conducted postdoctoral fellowships in molecular retrovirology at the Department of Biochemistry and Molecular Biology, OHSU, and in molecular neurobiology at the Vollum Institute for Advanced Biomedical Research. In 1988, Dr. Machida joined the faculty at OHSU and currently retains a primary appointment as Research Professor in the Department of Integrative Biosciences. Dr. Machida also holds an adjunct appointment in Biochemistry and Molecular Biology, OHSU.
Summary of Current Research
There is a limited understanding of the molecular mechanisms that regulate beta-adrenergic receptor (beta-AR) activation and expression in the central nervous system (CNS) and in the dysregulation of beta-ARs in depression. The beta 1-adrenergic receptor (beta 1-AR) is the primary beta-AR subtype found in the CNS and is expressed at multiple neuroanatomical locations, including the cortex, striatum, cerebellum, and thalamus. Alterations in adrenergic receptor number have been implicated in the pathophysiology of affective psychiatric disorders, including depression. Furthermore, beta-AR down-regulation occurs during chronic treatment with antidepressants, suggesting that the dysregulation of the beta1-AR subtype may be associated with depressive illness.
My laboratory has examined the molecular mechanisms underlying agonist-mediated beta 1-AR mRNA down-regulation, and has identified several potential transcriptional and post-transcriptional control mechanisms. Firstly, we have determined that specific RNA binding factors interact with the beta 1-AR mRNAs, and become induced in the presence of beta-AR agonist isoproterenol, resulting in the acceleration of beta 1-AR transcript degradation. Secondly, we have determined that exposure of cells to isoproterenol results in the rapid induction of inducible cyclic AMP early repressor (ICER). ICER can interact with elements of the beta 1-AR promoter region to repress beta 1-AR transcription. And thirdly, we have identified another transcriptional repressor region in the rat beta 1-AR gene, and have identified the repressor molecule as a nuclear LIM interactor - interacting factor. This novel factor contains a basic DNA-binding domain, including a leucine zipper motif (bZIP-like), and a phosphatase motif similar to those contained within the RNA polymerase II C-terminal domain (CTD) phosphatases. This research may provide insights in understanding the molecular mechanisms that control beta 1-AR regulation in the pathophysiology of affective psychiatric disorders.
- Ph.D., Oregon Health & Science University, 1982