Naiara Aquizu Lopez, Ph.D.

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
3501 Civic Center Boulevard
5052 Colket Translational Research Building
Philadelphia, PA 19104
Office: 215-590-2232
Fax: 215-590-3660
Lab: 267-425-3957
Fax: 215-590-3660
Lab: 267-425-3957
Email:
aquizun@chop.edu
aquizun@chop.edu
Publications
Education:
BS (Biology)
University Pompeu Fabra, Barcelona, 2005.
PhD (Biomedicine)
University of Barcelona, 2010.
Permanent linkBS (Biology)
University Pompeu Fabra, Barcelona, 2005.
PhD (Biomedicine)
University of Barcelona, 2010.
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
2. Gracia-Diaz C, Zhou Y, Yang Q, Lee C-H, Espana-Bonilla P, Zhang S, Padilla N, Fueyo R, Otrimski G, Li D, Sheppard S, Mark P, Harr MH, Hakonarson H, Rodan L, Jackson A, Vasudevan P, Powel C, Mohammed S, Maddirevula S, Alzaidan H, Faqeih EA, Efthymiou S, Turchetti V, Rahman F, Maqbool S, Salpietro V, Ibrahim SH, di Rosa G, Houlden H, Estaras C, Hurst ACE, Thompson ML, Chassevent A, Smith-Hicks CL, de la Cruz X, Holtz A, Torti E, Hajianpour MJ, Rieubland C, Braun D, Banka S, Heller EA, Saade M, Song H, Ming GL, Alkuraya FS, Maroofian R, Agrawal PB, Reinberg D, Bhoj EJ, Martinez-Balbas MA, Akizu N: Gain and loss of function variants in EZH1 disrupt neurogenesis timing and cause overlapping neurodevelopmental disorders. medRxiv 2022 Notes: ACCEPTED in Nat Commun.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 2022 Notes: In revision for JCI Insights.
Sheppard, S. E., Bryant, L., Wickramasekara, R. N., Vaccaro, C., Robertson, B., Hallgren, J., Hulen, J., Watson, C. J., Faundes, V., Duffourd, Y., Lee, P., Simon, M. C., de la Cruz, X., Padilla, N., Flores-Mendez, M., Akizu, N., Smiler, J., Pellegrino Da Silva, R., Li, D., March, M., Diaz-Rosado, A., Peixoto de Barcelos, I., Choa, Z. X., Lim, C. Y., Dubourg, C., Journel, H., Demurger, F., Mulhern, M., Akman, C., Lippa, N., Andrews, M., Baldridge, D., Constantino, J., van Haeringen, A., Snoeck-Streef, I., Chow, P., Hing, A., Graham, J. M., Jr., Au, M., Faivre, L., Shen, W., Mao, R., Palumbos, J., Viskochil, D., Gahl, W., Tifft, C., Macnamara, E., Hauser, N., Miller, R., Maffeo, J., Afenjar, A., Doummar, D., Keren, B., Arn, P., Macklin-Mantia, S., Meerschaut, I., Callewaert, B., Reis, A., Zweier, C., Brewer, C., Saggar, A., Smeland, M. F., Kumar, A., Elmslie, F., Deshpande, C., Nizon, M., Cogne, B., van Ierland, Y., Wilke, M., van Slegtenhorst, M., Koudijs, S., Chen, J. Y., Dredge, D., Pier, D., Wortmann, S., Kamsteeg, E. J., Koch, J., Haynes, D., Pollack, L., Titheradge, H., Ranguin, K., Denomme-Pichon, A. S., Weber, S., Perez de la Fuente, R., Sanchez Del Pozo, J., Lezana Rosales, J. M., Joset, P., Steindl, K., Rauch, A., Mei, D., Mari, F., Guerrini, R., Lespinasse, J., Tran Mau-Them, F., Philippe, C., Dauriat, B., Raymond, L., Moutton, S., Cueto-Gonzalez, A. M., Tan, T. Y., Mignot, C., Grotto, S., Renaldo, F., Drivas, T. G., Hennessy, L., Raper, A., Parenti, I., Kaiser, F. J., Kuechler, A., Busk, O. L., Islam, L., Siedlik, J. A., Henderson, L. B., Juusola, J., Person, R., Schnur, R. E., Vitobello, A., Banka, S., Bhoj, E. J. and Stessman, H. A. F: Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice. Science Advances March 10 2023.
Murielle Saade, Diego S Ferrero, José Blanco-Ameijeiras, Elena Gonzalez-Gobartt, Marco Flores-Mendez, Victor M Ruiz-Arroyo, Elena Martínez-Sáez, Santiago Ramón Y Cajal, Naiara Akizu, Nuria Verdaguer, Elisa Martí: Multimerization of Zika Virus-NS5 Causes Ciliopathy and Forces Premature Neurogenesis. Cell Stem Cell 27(6): 920-936, Dec 3 2020.
Guemez-Gamboa A, Çağlayan 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, November 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. Nature Genet 49((3)): 457-464, March 2017 Notes: Dr. Aquizu Lopez's name appears as Akizu Naiara in this citation.
Akizu Naiara, García Maria Alejandra, Estarás Conchi, Fueyo Raquel, Badosa Carmen, de la Cruz Xavier, Martínez-Balbás Marian A: EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21. Open Biol 6(4): 150227, April 2016 Notes: Dr. Aquizu Lopez's name appears as Akizu N. in this citation.
Guemez-Gamboa Alicia, Nguyen Long N, Yang Hongbo, Zaki Maha S, Kara Majdi, Ben-Omran Tawfeg, Akizu Naiara, Rosti Rasim Ozgur, Rosti Basak, Scott Eric, Schroth Jana, Copeland Brett, Vaux Keith K, Cazenave-Gassiot Amaury, Quek Debra Q Y, Wong Bernice H, Tan Bryan C, Wenk Markus R, Gunel Murat, Gabriel Stacey, Chi Neil C, Silver David L, Gleeson Joseph G: Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome. Nature Genet 47(7): 809-13, Jul 2015 Notes: Dr. Aquizu Lopez's name appears as Akizu Naiara in this citation.
Akizu Naiara, Cantagrel Vincent, Zaki Maha S, Al-Gazali Lihadh, Wang Xin, Rosti Rasim Ozgur, Dikoglu Esra, Gelot Antoinette Bernabe, Rosti Basak, Vaux Keith K, Scott Eric M, Silhavy Jennifer L, Schroth Jana, Copeland Brett, Schaffer Ashleigh E, Gordts Philip L S M, Esko Jeffrey D, Buschman Matthew D, Field Seth J, Napolitano Gennaro, Abdel-Salam Ghada M, Ozgul R Koksal, Sagıroglu Mahmut Samil, Azam Matloob, Ismail Samira, Aglan Mona, Selim Laila, Mahmoud Iman G, Abdel-Hadi Sawsan, Badawy Amera El, Sadek Abdelrahim A, Mojahedi Faezeh, Kayserili Hulya, Masri Amira, Bastaki Laila, Temtamy Samia, Müller Ulrich, Desguerre Isabelle, Casanova Jean-Laurent, Dursun Ali, Gunel Murat, Gabriel Stacey B, de Lonlay Pascale, Gleeson Joseph G: Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction. Nature Genet 47(5): 528-34, May 2015 Notes: Dr. Aquizu Lopez's name appears as Akizu Naiara in this citation.
Petazzi Paolo, Akizu Naiara, García Alejandra, Estarás Conchi, Martínez de Paz Alexia, Rodríguez-Paredes Manuel, Martínez-Balbás Marian A, Huertas Dori, Esteller Manel: An increase in MECP2 dosage impairs neural tube formation. Neurobiol Dis 67: 49-56, Jul 2014 Notes: Dr. Aquizu Lopez's name appears as Akizu Naiara in this citation.
Novarino Gaia, Fenstermaker Ali G, Zaki Maha S, Hofree Matan, Silhavy Jennifer L, Heiberg Andrew D, Abdellateef Mostafa, Rosti Basak, Scott Eric, Mansour Lobna, Masri Amira, Kayserili Hulya, Al-Aama Jumana Y, Abdel-Salam Ghada M H, Karminejad Ariana, Kara Majdi, Kara Bulent, Bozorgmehri Bita, Ben-Omran Tawfeg, Mojahedi Faezeh, Mahmoud Iman Gamal El Din, Bouslam Naima, Bouhouche Ahmed, Benomar Ali, Hanein Sylvain, Raymond Laure, Forlani Sylvie, Mascaro Massimo, Selim Laila, Shehata Nabil, Al-Allawi Nasir, Bindu P S, Azam Matloob, Gunel Murat, Caglayan Ahmet, Bilguvar Kaya, Tolun Aslihan, Issa Mahmoud Y, Schroth Jana, Spencer Emily G, Rosti Rasim O, Akizu Naiara, Vaux Keith K, Johansen Anide, Koh Alice A, Megahed Hisham, Durr Alexandra, Brice Alexis, Stevanin Giovanni, Gabriel Stacy B, Ideker Trey, Gleeson Joseph G: Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science 343(6170): 506-11, Jan 2014 Notes: Dr. Aquizu Lopez's name appears as Akizu Naiara in this citation.
Akizu Naiara, Cantagrel Vincent, Schroth Jana, Cai Na, Vaux Keith, McCloskey Douglas, Naviaux Robert K, Van Vleet Jeremy, Fenstermaker Ali G, Silhavy Jennifer L, Scheliga Judith S, Toyama Keiko, Morisaki Hiroko, Sonmez Fatma M, Celep Figen, Oraby Azza, Zaki Maha S, Al-Baradie Raidah, Faqeih Eissa A, Saleh Mohammed A M, Spencer Emily, Rosti Rasim Ozgur, Scott Eric, Nickerson Elizabeth, Gabriel Stacey, Morisaki Takayuki, Holmes Edward W, Gleeson Joseph G: AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder. Cell 154(3): 505-17, Aug 2013 Notes: Dr. Aquizu Lopez's name appears as Akizu Naiara in this citation.
Dixon-Salazar Tracy J, Silhavy Jennifer L, Udpa Nitin, Schroth Jana, Bielas Stephanie, Schaffer Ashleigh E, Olvera Jesus, Bafna Vineet, Zaki Maha S, Abdel-Salam Ghada H, Mansour Lobna A, Selim Laila, Abdel-Hadi Sawsan, Marzouki Naima, Ben-Omran Tawfeg, Al-Saana Nouriya A, Sonmez F Müjgan, Celep Figen, Azam Matloob, Hill Kiley J, Collazo Adrienne, Fenstermaker Ali G, Novarino Gaia, Akizu Naiara, Garimella Kiran V, Sougnez Carrie, Russ Carsten, Gabriel Stacey B, Gleeson Joseph G: Exome sequencing can improve diagnosis and alter patient management. Science Transl Med 4(138): 138ra78, Jun 2012 Notes: Dr. Aquizu Lopez's name appears as Akizu Naiara in this citation.
Novarino Gaia, Akizu Naiara, Gleeson Joseph G: Modeling human disease in humans: the ciliopathies. Cell 147(1): 70-9, Sep 2011 Notes: Dr. Aquizu Lopez's name appears as Akizu Naiara in this citation.
Akizu Naiara, Estarás Conchi, Guerrero Laura, Martí Elisa, Martínez-Balbás Marian A: H3K27me3 regulates BMP activity in developing spinal cord. Development 137(17): 2915-25, Sep 2010 Notes: Dr. Aquizu Lopez's name appears as Akizu Naiara in this citation.