PEOPLE

Naiara Aquizu Lopez, PhD

Assistant Professor of Pathology and Laboratory Medicine
Perelman School of Medicine at the University of Pennsylvania 

Contact InformationThe Children's Hospital of Philadelphia
3501 Civic Center Boulevard
5052 Colket Translational Research Building

Philadelphia, PA, 19104
Office: 215-590-2232
Fax: 215-590-3660

Email: aquizun@email.chop.edu

Itmat Expertise

The Akizu lab studies genetic and epigenetic mechanisms of neurodevelopmental and degenerative disorders that affect children. Our work begins with the identification of the genetic anomaly that causes a disease. We then generate human pluripotent stem cells derived neural models that we use for cellular and molecular studies, and animal models that serve to interrogate our questions in a physiologically complex system. Our ultimate goal is to translate our findings to therapies for brain disorders most of which are currently uncurable.

Research Expertise

OUR RESEARCH INTEREST:
To better understand human brain complexity in health and disease, with the ultimate goal to uncover therapeutic targets for neurological disorders.

KEYWORDS:
Neurogenetics, neurodegeneration, neural development, epigenetics, Polycomb, protein homeostasis, lipids, cell therapies, stem cells, organoids, mouse models of disease.

RESEARCH SUMMARY:
The exponential increase of genetic studies over the last decades has uncovered numerous genetic variants associated to neurological disorders. Often, these variants are widely expressed in every tissue and yet, they exclusively disrupt development, function or viability of specific neural populations. Indeed, specific neuronal vulnerability is surprisingly common in many neurological diseases. But, why are some neurons vulnerable to disease stimuli, and why are others resistant? What determines the response of each neural type to divers physiological and pathological conditions? And how does each neural type acquire and maintain specialized functions? The major goal of our lab is to gain insights into these fundamental questions. To achieve this goal, our current research is focused on uncovering functional and molecular features of cerebellar and motor neurons. These neuronal populations are particularly vulnerable to ubiquitous stimuli that alter protein synthesis and degradation, and lead to perinatal neurodegenerative disorders (i.e. cerebellar ataxias and spastic paraplegias). Treatment strategies for these disorders are limited and focused to the management of symptoms that eventually progress to devastating conditions that impose far-reaching social and economic burden. By combining animal models and human stem cell derived cellular cultures, and interrogating them with sequencing, proteomic and imaging methods our lab is uncovering neuronal subtype particularities in health and disease to better understand human brain complexity and advance in neurological disease treatment options.

OUR RESEARCH APPROACH:
Our current focus is in the study of neurodevelopmental and degenerative disorders. We combine animal models and human stem cell derived cultures, and apply DNA/RNA sequencing, epigenomics, proteomics and imaging methods to gain insights into functional and molecular differences between resistant and vulnerable cells. Information that we gather from these studies will serve to better understand disease mechanisms and develop treatment strategies.

OUR PROJECTS:
1. The role of EZH1 in neural development and disease
2. Protein and lipid homeostasis in the control of human brain function and complexity
3. Mechanisms that lead to generation of neuronal diversity during brain development and are perturbed in neurological diseases
4. Development of high-throughput experimental platform for functional validation of novel genetic variants

LAB PERSONNEL:
Principal investigator: Naiara Akizu, PhD
Research assistant: Sunyimeng Lei and Kelsey Walsh
Postdocs: Thomas Roule, PhD,
Graduate students: Carolina Garcia-Diaz, Vanessa Sanchez, Lilly Ryll
Undergraduate students: Songyi Lee




Education

BS (Biology), University Pompeu Fabra, Barcelona, 2005
PhD (Biomedicine), University of Barcelona, 2010

Specialty Certification

Postgraduate Training

Graduate Student; Epigenetics, Molecular Biology Institute of Barcelona, Spanish National Research Council, Department of Molecular Genomics, 2005-2010
Postdoctoral Fellow; Neurogenetics, University of California, San Diego, Department of Neurosciences, 2010-2014
Postdoctoral Fellow; Neural Development, The Scripps Research Institute, Department of Molecular and Cellular Neurosciences;, 2014-2016

Awards and Honors

Maximum Honor Prize, University Pompeu Fabra, Barcelona, Spain, 2005
Predoctoral Fellowship from Spanish National Research Council (I3P), 2006-2010
Summa cum laude in distinction of Doctoral Thesis, University of Barcelona, Spain, 2010
Postdoctoral Training Grant, California Institute of Regenerative Medicine, 2011-2013
K99/R00 NIH Pathway to Independence Award, The Scripps Research Institute, 2014-2017

Memberships and Professional Organizations

Grant review for Medical Research Council (MRC), UK., 2017 - 2017
Neurogenesis and Cell Fate Study Section, National Institute of Health (NIH), 2022 - 2022
ZRG1 BN-V Study Section, National Institute of Health (NIH), 2023 - 2023
ZRG1 BN-G Study Section, National Institute of Health (NIH), 2024 - 2024

Web Links


Selected Publications

Altered lipid homeostasis underlies selective neurodegeneration in SNX14 deficiency.

Zhou Y, Sanchez VB, Xu P, Flores-Mendez M, Ciesielski B, Yoo D, Teshome H, Henne M, O’Brien T, Mesaros C, Akizu N, bioRxiv, 2022

Loss of Protocadherin-12 Leads to Diencephalic-Mesencephalic Junction Dysplasia Syndrome.

Guemez-Gamboa A, Caglayan AO, Stanley V, Gregor A, Zaki MS, Saleem SN, Musaev D, McEvoy-Venneri J, Belandres D, Akizu N, Silhavy JL, Schroth J, Rosti RO, Copeland B, Lewis SM, Fang R, Issa MY, Per H, Gumus H, Bayram AK, Kumandas S, Akgumus GT, Erson-Omay EZ, Yasuno K, Bilguvar K, Heimer G, Pillar N, Shomron N, Weissglas-Volkov D, Porat Y, Einhorn Y, Gabriel S, Ben-Zeev B, Gunel M, Gleeson JG., Ann Neurol 84(5): 638-647, 2018, PMID:30178464

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Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing.

Lardelli RM, Schaffer AE, Eggens VR, Zaki MS, Grainger S, Sathe S, Van Nostrand EL, Schlachetzki Z, Rosti B, Akizu N, Scott E, Silhavy JL, Heckman LD, Rosti RO, Dikoglu E, Gregor A, Guemez-Gamboa A, Musaev D, Mande R, Widjaja A, Shaw TL, Markmiller S, Marin-Valencia I, Davies JH, de Meirleir L, Kayserili H, Altunoglu U, Freckmann ML, Warwick L, Chitayat D, Blaser S, Çağlayan AO, Bilguvar K, Per H, Fagerberg C, Christesen HT, Kibaek M, Aldinger KA, Manchester D, Matsumoto N, Muramatsu K, Saitsu H, Shiina M, Ogata K, Foulds N, Dobyns WB, Chi NC, Traver D, Spaccini L, Bova SM, Gabriel SB, Gunel M, Valente EM, Nassogne MC, Bennett EJ, Yeo GW, Baas F, Lykke-Andersen J, Gleeson JG, Nat Genet 49((3)): 457-464, 2017

EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21.

Akizu N, García MA, Estarás C, Fueyo R, Badosa C, de la Cruz X, Martínez-Balbás MA., Open Biol 6(4): 150227, 2016, PMID:27248655

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Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction.

Akizu N, Cantagrel V, Zaki MS, Al-Gazali L, Wang X, Rosti RO, Dikoglu E, Gelot AB, Rosti B, Vaux KK, Scott EM, Silhavy JL, Schroth J, Copeland B, Schaffer AE, Gordts PL, Esko JD, Buschman MD, Field SJ, Napolitano G, Abdel-Salam GM, Ozgul RK, Sagıroglu MS, Azam M, Ismail S, Aglan M, Selim L, Mahmoud IG, Abdel-Hadi S, Badawy AE, Sadek AA, Mojahedi F, Kayserili H, Masri A, Bastaki L, Temtamy S, Müller U, Desguerre I, Casanova JL, Dursun A, Gunel M, Gabriel SB, de Lonlay P, Gleeson JG., Nat Genet 47(5): 528-34, 2015, PMID:25848753

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Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome.

Guemez-Gamboa A, Nguyen LN, Yang H, Zaki MS, Kara M, Ben-Omran T, Akizu N, Rosti RO, Rosti B, Scott E, Schroth J, Copeland B, Vaux KK, Cazenave-Gassiot A, Quek DQ, Wong BH, Tan BC, Wenk MR, Gunel M, Gabriel S, Chi NC, Silver DL, Gleeson JG., Nat Genet 47(7): 809-13, 2015, PMID:26005868

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Exome sequencing can improve diagnosis and alter patient management.

Dixon-Salazar TJ, Silhavy JL, Udpa N, Schroth J, Bielas S, Schaffer AE, Olvera J, Bafna V, Zaki MS, Abdel-Salam GH, Mansour LA, Selim L, Abdel-Hadi S, Marzouki N, Ben-Omran T, Al-Saana NA, Sonmez FM, Celep F, Azam M, Hill KJ, Collazo A, Fenstermaker AG, Novarino G, Akizu N, Garimella KV, Sougnez C, Russ C, Gabriel SB, Gleeson JG., Science Transl Med 4(138): 138ra78, 2012, PMID:22700954

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AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder.

Akizu N, Cantagrel V, Schroth J, Cai N, Vaux K, McCloskey D, Naviaux RK, Van Vleet J, Fenstermaker AG, Silhavy JL, Scheliga JS, Toyama K, Morisaki H, Sonmez FM, Celep F, Oraby A, Zaki MS, Al-Baradie R, Faqeih EA, Saleh MA, Spencer E, Rosti RO, Scott E, Nickerson E, Gabriel S, Morisaki T, Holmes EW, Gleeson JG., Cell 154(3): 505-17, 2013, PMID:23911318

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Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders.

Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL, Heiberg AD, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al-Aama JY, Abdel-Salam GMH, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben-Omran T, Mojahedi F, El Din Mahmoud IG, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N, Al-Allawi N, Bindu PS, Azam M, Gunel M, Caglayan A, Bilguvar K, Tolun A, Issa MY, Schroth J, Spencer EG, Rosti RO, Akizu N, Vaux KK, Johansen A, Koh AA, Megahed H, Durr A, Brice A, Stevanin G, Gabriel SB, Ideker T, Gleeson JG., Science 343(6170): 506-11, 2014, PMID:24482476

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An increase in MECP2 dosage impairs neural tube formation.

Petazzi P, Akizu N, García A, Estarás C, Martínez de Paz A, Rodríguez-Paredes M, Martínez-Balbás MA, Huertas D, Esteller M., Neurobiol Dis 67(): 49-56, 2014, PMID:24657916

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Modeling human disease in humans: the ciliopathies.

Novarino G, Akizu N, Gleeson JG., Cell 147(1): 70-9, 2011, PMID:21962508

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H3K27me3 regulates BMP activity in developing spinal cord.

Akizu N, Estarás C, Guerrero L, Martí E, Martínez-Balbás MA., Development 137(17): 2915-25, 2010, PMID:20667911

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