Ismael Santa-Maria Perez, PhD

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Overview

Academic Appointments

  • Assistant Professor of Pathology and Cell Biology

Dr. Santa-Maria Perez is a biochemist with a Ph.D. in Molecular Biology. He heads a research laboratory investigating the role of microRNAs and post-transcriptional regulation in the onset and progression of neurodegenerative diseases.

Email: is2395@cumc.columbia.edu

Languages

  • Spanish

Credentials & Experience

Education & Training

  • PhD, 2008 Molecular Biology, Autonomous University of Madrid (Spain)

Honors & Awards

2008 - Spanish Royal Doctors Academy award
2009 - Neurological Diseases Research Centre Foundation and Queen Sofia Foundation’s Alzheimer’s Disease award
2012 - American Health Assistance Foundation Alzheimerʼs Disease Award
2013 - BrightFocus Foundation Alzheimerʼs Disease Award
2014 - Pilot Grant Award 
for Research on Alzheimer’s disease, aging, and related disorders
2015 - Alzheimer's Association New Investigator Research Grant

Research

Research in our laboratory is focused on understanding the mechanisms maintaining or altering tau proteostasis in neurons, and their relevance in aging and Alzheimer's disease (AD). Intracellular accumulation of neurofibrillary tangles of hyperphosphorylated misfolded tau proteins is one of the main hallmarks in many neurodegenerative diseases, including AD. Little is known about the mechanisms underlying tau dysfunction and neurofibrillary degeneration but a dysfunctional regulation of protein expression has been proposed to participate in the pathogenesis of AD and related tauopathies. In addition, it is unclear whether disturbances in the levels of microRNAs or other molecules that directly regulate tau proteostasis contribute to the pathogenesis of AD. Hence, investigating how certain microRNAs impact tau synthesis, hyperphosphorylation and accumulation in the disease is currently the main interest of our laboratory. In our research, we employ a variety of biochemical, cell culture, transgenic animal (Drosophila and mice) and molecular biology techniques to approach all these questions.

Grants

MICRORNA MODULATION OF TAU EXPRESSION AND PHOSPHORYLATION IN TAUOPATHY (PI: SANTA-MARIA, I)

1R01NS095922-01A1

Project Dates: Aug 1 2016 to May 31 2021

ADMIXTURE MAPPING IN LATE-ONSET ALZHEIMER S DISEASE (PI: TOSTO, G; Co-Investigator: SANTA-MARIA, I) 

1R21AG054832-01

Project Dates: Sep 30 2016 to Apr 30 2018

ROLE OF MICRORNAS IN THE REGULATION OF TAU PATHOLOGY (PI: SANTA-MARIA, I)

ALZA NIRG-15-364458

Project Dates: Feb 1 2016 to Jan 31 2018

POST-TRANSCRIPTIONAL REGULATION OF TAU IN AGING AND AD (PI: SMALL, S; Project 3 PI: Santa- Maria, I)

P50AG008702

Project Dates: June 1 2015 to May 31 2020

MICRORNA MODULATION OF TAU EXPRESSION AND PHOSPHORYLATION IN TAUOPATHY (Federal Gov)

Aug 1 2016 - May 31 2021

ADMIXTURE MAPPING IN LATE-ONSET ALZHEIMER S DISEASE (Federal Gov)

Sep 30 2016 - Apr 30 2019

ROLE OF MICRORNAS IN THE REGULATION OF TAU PATHOLOGY (Private)

Feb 1 2016 - Jan 31 2018

ROLE OF MICRORNAS IN TANGLE PREDOMINANT ALZHEIMER S DISEASE (Private)

Jul 1 2012 - Jun 30 2014

FACULTY RECRUITMENT ON THE NEUROBIOLOGY OF AGING (Federal Gov)

Sep 30 2009 - Aug 31 2012

Selected Publications

Santa-Maria I., Alaniz M.E., Renwick N., Cela C., Fulga T.A., Van Vactor D., Tuschl T., Clark L.N., Shelanski M.L., McCabe B.D., Crary J.F. Dysregulation of microRNA-219 promotes neurodegeneration through post-transcriptional regulation of tau. Journal of Clinical Investigation. 2015; 125(2): 681-686. Highlighted in “Crucial role for miR-219 in the development of tauopathies” Nature Reviews Neurology. 2015; 11, 68. 

Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, Arnold SE, Attems J, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Gearing M, Grinberg LT, Hof PR, Hyman BT, Jellinger K, Jicha GA, Kovacs GG, Knopman DS, Kofler J, Kukull WA, Mackenzie IR, Masliah E, McKee A, Montine TJ, Murray ME, Neltner JH, Santa-Maria I, Seeley WW, Serrano-Pozo A, Shelanski ML, Stein T, Takao M, Thal DR, Toledo JB, Troncoso JC, Vonsattel JP, White CL 3rd, Wisniewski T, Woltjer RL, Yamada M, Nelson PT. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol. 2014;128(6):755-66

Santa-Maria I., Haggiagi A., Liu X., Wasserscheid J., Nelson PT., Dewar K., Clark LN., Crary JF. The MAPT H1 haplotype is associated with tangle-predominant dementia. Acta Neuropathologica. 2012; 124(5): 693-704

Santa-Maria I., Varghese M., Ksiezak-Reding H., Dzhun A., Wang J., Pasinetti GM. Paired helical filaments from Alzheimer disease brain induce intracellular accumulation of Tau protein in aggresomes. Journal of Biological Chemistry. 2012; 287(24): 20522-33

Santa-Maria I., Diaz-Ruiz C., Ksiezak-Reding H., Cheng A., Ho L., Wang J., Pasinetti G.M. GSPE interferes with tau aggregation in vivo: implication for treating tauopathy. Neurobiology of Aging. 2012; 33(9): 2072-81

Ksiezak-Reding H., Ho L., Santa-Maria I., Diaz-Ruiz C., Wang J., Pasinetti G.M. Ultrastructural alterations of Alzheimer’s disease paired helical filaments by grape seed polyphenols. Neurobiology of Aging. 2012; 33(7): 1427-39

Wang J*., Santa-Maria I.*, Ksiezak-Reding H., Ho L., Pasinetti G.M. Grape Derived Polyphenols Attenuate Tau Neuropathology in a Mouse Model of Alzheimer's Disease. Journal of Alzheimer´s Disease. 2010; 22(2): 653-61. [*co-authors]

Santa-Maria I., Avila J., Rabano A. Differential gene expression analysis of human entorhinal cortex support a possible role of some extracellular matrix proteins in the onset of Alzheimer disease. Neuroscience Letters. 2010; 468 (3): 225-228.

Perez M*., Santa-Maria I.*, Gomez de Barreda E., Zhu X., Cuadros R., Roman Cabrero J., Sanchez-Madrid F., Dawson HN., Vitek MP., Perry G., Smith MA., Avila J. Tau, an inhibitor of deacetylase HDAC6 function. Journal of Neurochemistry. 2009; 109 (6): 1756-1766. [*co-authors]

Santa-Maria I., Santpere G., MacDonald M. J., Gomez de Barreda E., Felix Hernandez F., Moreno F. J., Ferrer I., Avila J. Coenzyme Q as an inducer in vivo of tau aggregation, tau filaments and Hirano bodies. Journal of Neuropathology and Experimental Neurology. 2008; 67 (5): 428-434.

Mondragón-Rodríguez S., Basurto-Islas G., Santa-Maria I., Mena R., Binder L. I., Avila J., Smith M. A., Perry G., García-Sierra F. Cleavage and Conformational Changes of Tau Protein Follow Phosphorylation During Alzheimer´s Disease. International Journal of Experimental Pathology. 2008; 89 (2): 81-90

Santa-Maria I., Hernandez F., Del Rio J., Moreno F.J., Avila J. Tramiprosate, a drug of potential interest for the treatment of Alzheimer's disease, promotes an abnormal aggregation of tau. Molecular Neurodegeneration. 2007; 2 (1): 17. http://www.alzforum.org/news/research-news/alzhemed-tangles-tau-too

Santa-Maria I., Perez M., Hernandez F., Munoz V., Moreno F.J., Avila J. In vitro tau fibrillization: mapping protein regions. Biochimica et Biophysica Acta. 2006; 1762 (7): 683-692.

Santa-Maria I., Smith M.A., Perry G., Hernandez F., Avila J., Moreno F.J. Effect of quinones on microtubule polymerization: a link between oxidative stress and cytoskeletal alterations in Alzheimer's disease. Biochimica et Biophysica Acta. 2005; 1740 (3): 472-80.

Mendieta J., Fuertes M.A., Kunjishapatham R., Santa-Maria I., Moreno F.J., Alonso C., Gago F., Munoz V., Avila J., Hernandez F. Phosphorylation modulates the alpha-helical structure and polymerization of a peptide from the third tau microtubule-binding repeat. Biochimica et Biophysica Acta. 2005; 1721 (1-3): 16-26.

Santa-Maria I., Hernandez F., Martin C.P., Avila J., Moreno F.J. Quinones facilitate the self-assembly of the phosphorylated tubulin binding region of tau into fibrillar polymers. Biochemistry. 2004; 43 (10): 2888-97.