Naiara Aquizu Lopez, Ph.D.

faculty photo
Assistant Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
The 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
Lab: 267-425-3957
Education:
BS (Biology)
University Pompeu Fabra, Barcelona, 2005.
PhD (Biomedicine)
University of Barcelona, 2010.
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Description of 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

Selected Publications

Zhou Y, Sanchez VB, Xu P, Flores-Mendez M, Ciesielski B, Yoo D, Teshome H, Henne M, O’Brien T, Mesaros C, Akizu N: Altered lipid homeostasis underlies selective neurodegeneration in SNX14 deficiency. bioRxiv Dec 2022 Notes: Accepted in JCI Insight.

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.: Loss of Protocadherin-12 Leads to Diencephalic-Mesencephalic Junction Dysplasia Syndrome. Ann Neurol 84(5): 638-647, Nov 2018.

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: Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing. Nat Genet 49((3)): 457-464, Mar 2017.

Akizu N, García MA, Estarás C, Fueyo R, Badosa C, de la Cruz X, Martínez-Balbás MA.: EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21. Open Biol 6(4): 150227, April 2016.

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.: Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome. Nat Genet 47(7): 809-13, Jul 2015.

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.: Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction. Nat Genet 47(5): 528-34, May 2015.

Petazzi P, Akizu N, García A, Estarás C, Martínez de Paz A, Rodríguez-Paredes M, Martínez-Balbás MA, Huertas D, Esteller M.: An increase in MECP2 dosage impairs neural tube formation. Neurobiol Dis 67: 49-56, Jul 2014.

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.: Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science 343(6170): 506-11, Jan 2014.

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.: AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder. Cell 154(3): 505-17, Aug 2013.

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.: Exome sequencing can improve diagnosis and alter patient management. Science Transl Med 4(138): 138ra78, Jun 2012.

Novarino G, Akizu N, Gleeson JG.: Modeling human disease in humans: the ciliopathies. Cell 147(1): 70-9, September 2011.

Akizu N, Estarás C, Guerrero L, Martí E, Martínez-Balbás MA.: H3K27me3 regulates BMP activity in developing spinal cord. Development 137(17): 2915-25, Sep 2010.

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Last updated: 03/18/2024
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