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Genetics Faculty


Ashleigh Schaffer
Assistant Professor
Ph.D. Training Faculty
Department of Genetics
School of Medicine
Case Western Reserve University
Biomedical Research Building 727
2109 Adelbert Road
Cleveland, Ohio 44106-4955
Tel: (216) 368-1892
Fax: (216) 368-3432
E-mail: ashleigh.schaffer@case.edu


About Ashleigh Schaffer

Ashleigh Schaffer graduated with a B.S. in Genetics from University of Wisconsin-Madison and went on to earn her Ph.D. from the University of California, Irvine under the mentorship of Dr. Maike Sander, where she studied transcription factor-mediated mechanisms of cell fate determination in the pancreas. She then continued her training as a postdoctoral fellow at the University of California, San Diego, and Howard Hughes Medical Institute under the guidance of Dr. Joseph G. Gleeson, focused on elucidating the genetic cause, and molecular mechanisms, underlying recessive pediatric neurological disease. During her time with Dr. Gleeson, Ashleigh discovered over 20 novel genetic causes of disease, many of which occurred in proteins that bind to RNA. She was then awarded an NIH K99/R00 Pathway to Independence grant to delve further into RNA-mediated pediatric neurological disease mechanisms in the lab of Gene Yeo at University of California, San Diego. She joined the Department of Genetics and Genomes Sciences at Case Western Reserve University as an Assistant Professor in February 2017. She has a secondary appointment in the Center for RNA Science and Therapeutics.


Research

It has long been assumed that ubiquitously expressed proteins, like those that regulate RNA transcription and translation, function in a conserved manner across tissues and between species. Thus, severe, damaging mutations would lead to systemic phenotypes and cause lethality in humans. Contrary to this idea, we have identified patients with tissue specific disorders harboring variants in a variety of ubiquitously expressed proteins. This finding indicates ubiquitous proteins may function, or regulate, cellular processes in a cell type specific manner.

Our laboratory is primarily interested in understanding the unique functions of ubiquitously expressed proteins in human brain development and pediatric neurological disease. We focus on a set of ubiquitously expressed proteins that regulate RNA biogenesis, stability, and protein translation called RNA binding proteins. We use a variety of animal and stem cell models to investigate protein function on a gross and molecular scale.

Additionally, we aim to uncover new mechanisms of neurological disease through genetic and functional studies conducted in collaboration with our local hospitals.


Selected Publications

Access the recommendation on F1000Prime Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration.
Schaffer AE, Breuss MW, Caglayan AO, Al-Sanaa N, Al-Abdulwahed HY, Kaymakçalan H, Yılmaz C, Zaki MS, Rosti RO, Copeland B, Baek ST, Musaev D, Scott EC, Ben-Omran T, Kariminejad A, Kayserili H, Mojahedi F, Kara M, Cai N, Silhavy JL, Elsharif S, Fenercioglu E, Barshop BA, Kara B, Wang R, Stanley V, James KN, Nachnani R, Kalur A, Megahed H, Incecik F, Danda S, Alanay Y, Faqeih E, Melikishvili G, Mansour L, Miller I, Sukhudyan B, Chelly J, Dobyns WB, Bilguvar K, Jamra RA, Gunel M, Gleeson JG
Nat Genet (2018);
See PubMed abstract

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 (2017);:
See PubMed abstract

An AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development.
Baek ST, Copeland B, Yun EJ, Kwon SK, Guemez-Gamboa A, Schaffer AE, Kim S, Kang HC, Song S, Mathern GW, Gleeson JG
Nat Med (2015);21(12):1445-54
See PubMed abstract

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 (2015);47(5):528-34
See PubMed abstract

Mutations in KATNB1 cause complex cerebral malformations by disrupting asymmetrically dividing neural progenitors.
Mishra-Gorur K, Çağlayan AO, Schaffer AE, Chabu C, Henegariu O, Vonhoff F, Akgümüş GT, Nishimura S, Han W, Tu S, Baran B, Gümüş H, Dilber C, Zaki MS, Hossni HA, Rivière JB, Kayserili H, Spencer EG, Rosti RÖ, Schroth J, Per H, Çağlar C, Çağlar Ç, Dölen D, Baranoski JF, Kumandaş S, Minja FJ, Erson-Omay EZ, Mane SM, Lifton RP, Xu T, Keshishian H, Dobyns WB, Chi NC, Šestan N, Louvi A, Bilgüvar K, Yasuno K, Gleeson JG, Günel M
Neuron (2014);84(6):1226-39
See PubMed abstract

CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration.
Schaffer AE, Eggens VR, Caglayan AO, Reuter MS, Scott E, Coufal NG, Silhavy JL, Xue Y, Kayserili H, Yasuno K, Rosti RO, Abdellateef M, Caglar C, Kasher PR, Cazemier JL, Weterman MA, Cantagrel V, Cai N, Zweier C, Altunoglu U, Satkin NB, Aktar F, Tuysuz B, Yalcinkaya C, Caksen H, Bilguvar K, Fu XD, Trotta CR, Gabriel S, Reis A, Gunel M, Baas F, Gleeson JG
Cell (2014);157(3):651-63
See PubMed abstract

Novel mutation in the fukutin gene in an Egyptian family with Fukuyama congenital muscular dystrophy and microcephaly.
Ismail S, Schaffer AE, Rosti RO, Gleeson JG, Zaki MS
Gene (2014);539(2):279-82
See PubMed abstract

A homozygous IER3IP1 mutation causes microcephaly with simplified gyral pattern, epilepsy, and permanent neonatal diabetes syndrome (MEDS).
Abdel-Salam GM, Schaffer AE, Zaki MS, Dixon-Salazar T, Mostafa IS, Afifi HH, Gleeson JG
Am J Med Genet A (2012);158A(11):2788-96
See PubMed abstract

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
Sci Transl Med (2012);4(138):138ra78
See PubMed abstract