Ivana Delalle. M.D., Ph.D
Tel. 617 414 7014
- Pathology/Neuropathology residency/fellowship, Massachussets General Hospital, Harvard Medical School;
- M.D./ Ph.D, School of Medicine, University of Zagreb, Croatia
I. miRNAs in schizophrenia and bipolar disorder
This project (funded by R21 NIH MH 86079) applies a novel approach towards the search for biological markers for bipolar disorder (BD) and schizophrenia (SZ). MicroRNAs regulate genes involved in brain functions negatively affected in neuropsychiatric disorders. Exosomes are cellular secretory vesicles containing miRNAs. Once secreted, exosomes are able to attach to recipient cells and release miRNAs potentially modulating the function of the recipient cell. Thus, exosomal miRNA expression in brains of patients diagnosed with SZ and BD may differ from controls, reflecting either disease-specific or common aberrations in SZ and BD patients. Exosomal miRNAs from frozen postmortem cortical samples with well-preserved RNA is isolated and submitted to profiling by Luminex FLEXMAP 3D microfluidic device. Multiple statistical analyses of microarray data suggest that certain exosomal miRNAs were differentially expressed in SZ and BD subjects in comparison to controls. RT-PCR validation confirmed that certain miRNAs have significantly changed expression when compared to control samples (manuscript in submission). We perform these studies in collaboration with Dr. Vanderburg, Director of Advanced Tissue Research Center at Harvard NeuroDiscovery Center.
II. cytoskeleton and Alzheimer’s disease
Brain Derived Neurotrophic Factor (BDNF) and its receptor Tyrosine kinase B (TrkB) may influence brain reserve, the ability of the brain to tolerate pathological changes without significant decline in function. We explore whether a specifically vulnerable population of human neurons shows a compensatory response to the neuropathological changes of Alzheimer Disease (AD) and whether that response depends on an up-regulation of the BDNF pathway. As BDNF/TrkB signaling affects memory formation and retention through modification of the actin cytoskeleton, we also examine the expression of actin capping protein beta 2 (Capzb2), a marker of actin cytoskeleton reorganization. We perform these studies in collaboration with Dr. Seshadri, Professor of Neurology at BUSM and Framingham Heart Study investigator. This work is partially supported by PHS grant T32 AG00015-21.
- Kao PF, Banigan MG, Vanderburg CR, McKee AC, Polgar P, Seshadri S, and Delalle I: Increased expression of TrkB and Capzb2 accompanies preserved cognitive status in early Alzheimer’s disease pathology (accepted for publication in Journal of Neuropathology and Experimental Neurology 2012).
- Kao PF, Davis DA, Banigan MG, Vanderburg CR, Seshadri S, and Delalle I: Modulators of cytoskeletal reorganization in CA1 hippocampal neurons show increased expression in patients at mid-stage Alzheimer’s disease. PLoS One 2010 Oct 13;5(10):e13337.
- Davis DA, Wilson MH, Giraud J, Xie Z, Tseng H-C, England C, Hersckovitz H, Tsai L-H, and Delalle I: Capzb2 interacts with ß-tubulin to regulate growth cone morphology and neurite outgrowth. PLoS Biol 7(10) 2009; e1000208. doi:10.1371/journal.pbio.1000208.
- Graeff J, Guan J-S, Rei D, Wang W-Y, Hennig KM, Nieland TJF, Fass DJ, Kao PF, Kahn M, Joseph N, Haggarty SJ, Delalle I, and Tsai L-H: An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 2012; 483:222-226.
- Zovoilis A, Agbemenyah HY, Agis-Balboa RC, Stilling RM , Rao P , Edbauer D, Farinelli L, Delalle I , Schmitt A, Falkai P, Bahari-Javan, S Burkhardt S , Sananbenesi F, and Fischer A: microRNA-34c is a novel target to treat dementias. The EMBO J 2011;30(20):4299-308.
- Vanderburg CR, Davis DA, Diamond RE, Kao PF, and Delalle I: Capzb2 protein expression in the brains of patients diagnosed with Alzheimer’s disease and Huntington’s disease. Translational Neuroscience 2010; 1(1): 55-58.