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Genetics Faculty


Helen Miranda
Assistant Professor
Department of Genetics
School of Medicine
Case Western Reserve University
Biomedical Research Building 719
2109 Adelbert Road
Cleveland, Ohio 44106-4955
Tel: (216) 368-8811
Fax: (216) 368-3432
E-mail: helen.miranda@case.edu


About Helen Miranda

Helen Miranda graduated with a B.S. in Biomedicine and a M.S. in Immunopathology from the State University of Londrina In Brazil. She then went to earn her PhD in Cell and Molecular Biology in the University of Sao Paulo, also in Brazil, under the mentorship of Dr. Lewis Joel Greene. In her graduate work, Helen performed proteomics comparisons of Adult Stem Cells from two different sources (bone marrow and umbilical cord vein). As a graduate student, Helen was one of only 10 Brazilians selected by the renowned stem cell biology experts in the UK for the "Embryonic Stem (ES) Cells as a Model System for Embryonic Development" course. During this experience, she became fascinated by the use of induced pluripotent stem cells (iPSCs) for modeling human diseases. For that reason, Helen chose to come to the USA as a joint postdoctoral fellow in the La Spada lab and in the Muotri lab at the University of California San Diego (UCSD). During her postdoctoral training, Helen developed stem cell models for two different motor neuron disorders, spinal bulbar muscular atrophy and amyotrophic lateral sclerosis. She joined the Department of Genetics and Genomes Sciences at Case Western Reserve University as an Assistant Professor in May 2018 to continue her studies on the pathophysiology of motor neuron diseases.


Research

A substantial number of drugs found to alleviate symptoms of motor neuron diseases (MNDs) in animal models have failed in clinical trials. While the reasons for this are not clear, modeling with disease cell types from affected patients may yield novel targets and pathways, and setting the stage for the discovery of drugs targeting MNDs. Our lab focus on the investigations of cell autonomous and non-cell autonomous molecular events involved in spinal bulbar muscular atrophy and amyotrophic lateral sclerosis using induced pluripotent stem cell (iPSC) models. New advents in stem cell research currently include the possibility of exploring co-cultures of multiple cell types to study their interactions. Therefore, our lab uses iPSCs developed for SBMA and ALS8 to dissect the contributions of motor neurons, astrocytes and skeletal muscles for motor neuron diseases.


Selected Publications

Badders NM, Korff A, Miranda HC, Vuppala PK, Smith RB, Winborn BJ, Quemin ER, Sopher BL, Dearman J, Messing J, Kim NC, Moore J, Freibaum BD, Kanagaraj AP, Fan B, Tillman H, Chen PC, Wang Y, Freeman BB, Li Y, Kim HJ, La Spada AR, Taylor JP (2018)
Selective modulation of the androgen receptor AF2 domain rescues degeneration in spinal bulbar muscular atrophy.
Nat Med;24(4):427-437
See PubMed abstract

Polanco MJ, Parodi S, Piol D, Stack C, Chivet M, Contestabile A, Miranda HC, Lievens PM, Espinoza S, Jochum T, Rocchi A, Grunseich C, Gainetdinov RR, Cato AC, Lieberman AP, La Spada AR, Sambataro F, Fischbeck KH, Gozes I, Pennuto M (2016)
Adenylyl cyclase activating polypeptide reduces phosphorylation and toxicity of the polyglutamine-expanded androgen receptor in spinobulbar muscular atrophy.
Sci Transl Med;8(370):370ra181
See PubMed abstract

Dickey AS, Pineda VV, Tsunemi T, Liu PP, Miranda HC, Gilmore-Hall SK, Lomas N, Sampat KR, Buttgereit A, Torres MJ, Flores AL, Arreola M, Arbez N, Akimov SS, Gaasterland T, Lazarowski ER, Ross CA, Yeo GW, Sopher BL, Magnuson GK, Pinkerton AB, Masliah E, La Spada AR (2016)
PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically.
Nat Med;22(1):37-45
See PubMed abstract

Todd TW, Kokubu H, Miranda HC, Cortes CJ, La Spada AR, Lim J (2015)
Nemo-like kinase is a novel regulator of spinal and bulbar muscular atrophy.
Elife;4:e08493
See PubMed abstract

Cortes CJ, Miranda HC, Frankowski H, Batlevi Y, Young JE, Le A, Ivanov N, Sopher BL, Carromeu C, Muotri AR, Garden GA, La Spada AR (2014)
Polyglutamine-expanded androgen receptor interferes with TFEB to elicit autophagy defects in SBMA.
Nat Neurosci;17(9):1180-9
See PubMed abstract

Miranda HC, Herai RH, Thomé CH, Gomes GG, Panepucci RA, Orellana MD, Covas DT, Muotri AR, Greene LJ, Faça VM (2012)
A quantitative proteomic and transcriptomic comparison of human mesenchymal stem cells from bone marrow and umbilical cord vein.
Proteomics;12(17):2607-17
See PubMed abstract

Nunes SO, Itano EN, Amarante MK, Reiche EM, Miranda HC, de Oliveira CE, Matsuo T, Vargas HO, Watanabe MA (2008)
RNA from Borna disease virus in patients with schizophrenia, schizoaffective patients, and in their biological relatives.
J Clin Lab Anal;22(4):314-20
See PubMed abstract

Reiche EM, Ehara Watanabe MA, Bonametti AM, Kaminami Morimoto H, Akira Morimoto A, Wiechmann SL, Breganó JW, Matsuo T, Vissoci Reiche F, Miranda HC, Brajão Oliveira K, Vogler IH, Siscar AR (2006)
The effect of stromal cell-derived factor 1 (SDF1/CXCL12) genetic polymorphism on HIV-1 disease progression.
Int J Mol Med;18(4):785-93
See PubMed abstract

Miranda HC, Nunes SO, Calvo ES, Suzart S, Itano EN, Watanabe MA (2006)
Detection of Borna disease virus p24 RNA in peripheral blood cells from Brazilian mood and psychotic disorder patients.
J Affect Disord;90(1):43-7
See PubMed abstract

Zimiani K, Guarnier FA, Miranda HC, Watanabe MA, Cecchini R (2005)
Nitric oxide mediated oxidative stress injury in rat skeletal muscle subjected to ischemia/reperfusion as evaluated by chemiluminescence.
Nitric Oxide;13(3):196-203
See PubMed abstract