Alexander Bassuk, MD, PhD

Alexander Bassuk, MD, PhDPI and Director, CTSA KL2 Program

Professor, Division of Pediatric Neurology

Professor of Pediatrics – Neurology

Professor of Neurology

Personal statement

I am a pediatric neurologist and my laboratory focuses on the neuroanatomy, molecular biology, protein biochemistry, and genetic mechanisms in human diseases and animal models. I am currently PI on 4 NIH R01 awards. I have trained multiple medical students, resident and fellow researchers, and graduated three PhD students.

Currently I am mentoring two MSTP students, one junior faculty on the K08, and one junior faculty on a KL2, and I serve on nine thesis committees. I have been the recruiter for University of Iowa’s Child Health Research Career Development Award since 2011 and have mentored all junior faculty K12 Pediatrician-scholars during this time (6 K12 funded physician-scientists). I am involved with under-represented minority (URM) recruiting at all levels at the University of Iowa. I have the expertise and the enthusiasm needed to guide KL2 scholars.


  • Fundamental: Issues and Texts BA – University of Chicago, 1991
  • Biology: Pathology PhD – University of Chicago, 1996
  • Medicine MD – University of Chicago, 1999
  • Pediatrics Resident – Northwestern University Children’s Memorial Hospital, 2001
  • Neurology, Child Neurology Resident – Northwestern University Children’s Memorial Hospital, 2004


  • Graduate Student, Jeffrey Leiden, MD, PhD, Supervisor, University of Chicago (1992-1996)
  • Resident in Pediatrics, Children’s Memorial Hospital, Northwestern University (1999-2001)
  • Resident in Pediatric Neurology, Children’s Memorial Hospital, Northwestern University (2001-2004)
  • Instructor of Pediatrics and Neurology, Northwestern University (2004-2005)
  • Assistant Professor Neurology and Pediatrics, Center for Genetic Medicine, Northwestern University (2005-2007)
  • Assistant Professor Pediatrics, Division of Neurology, Interdisciplinary Graduate Program in Genetics, Interdisciplinary Graduate Program in Neuroscience, Medical Scientist Training Program (MSTP), and Molecular and Cellular Biology Graduate Program, University of Iowa (2007-2011)
  • Associate Professor Pediatrics, Division of Neurology, Interdisciplinary Graduate Program in Genetics, Interdisciplinary Graduate Program in Neuroscience, Medical Scientist Training Program (MSTP), and Molecular and Cellular Biology Graduate Program, University of Iowa (2011-2016)
  • Stead Family Professor of Pediatric Neurology, Professor of Pediatrics, Division of Neurology, Interdisciplinary Graduate Program in Genetics, Interdisciplinary Graduate Program in Neuroscience, Medical Scientist Training Program (MSTP), and Molecular and Cellular Biology Graduate Program, University of Iowa (2016-Present)


  • Early Acceptance Program, University of Chicago (1988)
  • Richter Award for Undergraduate Research, University of Chicago (1988)
  • Student Marshall, University of Chicago (1990)
  • A.B., Highest Honors in Fundamentals: Issues & Texts, University of Chicago (1991)
  • Phi Beta Kappa, University of Chicago (1991)
  • NIH-MSTP Scholarship, University of Chicago (1991)
  • National Defense Science and Engineering Graduate Fellowship, DOD (1994)
  • Leon E. Ledbetter Prize for Most Outstanding Research Contribution by a Senior Medical Student, University of Chicago (1999)
  • Mentored Clinical Scientist Development Award (KO8), NIH/NINDS (2004)
  • Young Investigator Award, Northwestern Memorial Faculty Foundation (2005)
  • Ad hoc reviewer for NIH Study Section, Genetics of Human Disease (GHD), NIH (2009)
  • Permanent Study Section member, Genetics of Human Disease (GHD), October 2011-present, NIH (2011)

Contribution to science

Elucidating the role of PRICKLE mutations in epilepsy

We discovered a mutation in the PRICKLE1 gene in several families with epilepsy. Subsequently, we showed that altering Prickle expression in various model organisms (i.e., fruit flies, zebrafish, mice and humans) can trigger an epilepsy phenotype. When evaluating novel anti-seizure therapies, the evolutionarily conserved nature of the prickle/epilepsy pathway allows us to move rapidly from fly, to fish, to mouse, poising us for a speedy translation to human studies. The proposed studies should not only uncover novel therapeutic strategies, but also elucidate basic mechanisms underlying seizure regulation, across evolution. These studies should have immediate implications for epilepsy patients, particularly those with mutations in Prickle-pathway genes. In a broader sense, however, by uncovering a protein network that is perturbed in epileptics in general, we will illuminate new avenues of research that are globally applicable to all patients with epilepsy.                                                                                                                                                                               

  • Bassuk AG, Wallace RH, Buhr A, Buller AR, Afawi Z, Shimojo M, Miyata S, Chen S, Gonzalez-Alegre P, Griesbach HL, Wu S, Nashelsky M, Vladar EK, Antic D, Ferguson PJ, Cirak S, Voit T, Scott MP, Axelrod JD, Gurnett C, Daoud AS, Kivity S, Neufeld MY, Mazarib A, Straussberg R, Walid S, Korczyn AD, Slusarski DC, Berkovic SF, El-Shanti HI. A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome. Am J Hum Genet. 2008 Nov;83(5):572-81. PMID: 18976727; PMCID: PMC2668041.
  • Tao H, Manak JR, Sowers L, Mei X, Kiyonari H, Abe T, Dahdaleh NS, Yang T, Wu S, Chen S, Fox MH, Gurnett C, Montine T, Bird T, Shaffer LG, Rosenfeld JA, McConnell J, Madan-Khetarpal S, Berry-Kravis E, Griesbach H, Saneto RP, Scott MP, Antic D, Reed J, Boland R, Ehaideb SN, El-Shanti H, Mahajan VB, Ferguson PJ, Axelrod JD, Lehesjoki AE, Fritzsch B, Slusarski DC, Wemmie J, Ueno N, Bassuk AG. Mutations in prickle orthologs cause seizures in flies, mice, and humans. Am J Hum Genet. 2011 Feb 11;88(2):138-49. PMID: 21276947; PMCID: PMC3035715.​
  • Ehaideb SN, Iyengar A, Ueda A, Iacobucci GJ, Cranston C, Bassuk AG, Gubb D, Axelrod JD, Gunawardena S, Wu CF, Manak JR. prickle modulates microtubule polarity and axonal transport to ameliorate seizures in flies. Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):11187-92. PMID: 25024231; PMCID: PMC4121842.​
  • Paemka L, Mahajan VB, Ehaideb SN, Skeie JM, Tan MC, Wu S, Cox AJ, Sowers LP, Gecz J, Jolly L, Ferguson PJ, Darbro B, Schneider A, Scheffer IE, Carvill GL, Mefford HC, El-Shanti H, Wood SA, Manak JR, Bassuk AG. Seizures are regulated by ubiquitin-specific peptidase 9 X-linked (USP9X), a de-ubiquitinase. PLoS Genet. 2015 Mar;11(3):e1005022. PMID: 25763846; PMCID: PMC4357451.

PRICKLE genes in autism

We sequenced PRICKLE2 in a cohort of patients with autism spectrum disorders (ASDs), identifying two families harboring PRICKLE2 variants not in our control population. Notably, in complementation assays of hippocampal neurons from Prickle2-null mice, wild-type Prickle2 rescued neuronal defects, but the two PRICKLE2 variants rescued neither the abnormal morphology nor abnormal spontaneous quantal synaptic activity, suggesting patient variants lacked critical functions. We also examined PRICKLE2 alleles in the autism patients to reveal that rare-protein-sequence-altering variants were significantly overrepresented compared to controls. These findings are particularly relevant because 30% of all ASD patients also have epilepsy; and although few genes are known to contribute to both ASDs and epilepsy, perturbation of the signaling pathways that regulate synaptic development and function are implicated in the etiology of both disorders. In related studies, a yeast 2-hybrid screen revealed Prickle1 physically interacts with Synapsin1 a protein that when mutated in mice and humans leads to both epilepsy and ASD phenotypes

  • Paemka L, Mahajan VB, Skeie JM, Sowers LP, Ehaideb SN, Gonzalez-Alegre P, Sasaoka T, Tao H, Miyagi A, Ueno N, Takao K, Miyakawa T, Wu S, Darbro BW, Ferguson PJ, Pieper AA, Britt JK, Wemmie JA, Rudd DS, Wassink T, El-Shanti H, Mefford HC, Carvill GL, Manak JR, Bassuk AG. PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders. PLoS One. 2013;8(12):e80737. PMID: 24312498; PMCID: PMC3849077.
  • Sowers LP, Loo L, Wu Y, Campbell E, Ulrich JD, Wu S, Paemka L, Wassink T, Meyer K, Bing X, El-Shanti H, Usachev YM, Ueno N, Manak JR, Shepherd AJ, Ferguson PJ, Darbro BW, Richerson GB, Mohapatra DP, Wemmie JA, Bassuk AG. Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction. Mol Psychiatry. 2013 Oct;18(10):1077-89. PMID: 23711981; PMCID: PMC4163749.
  • Sowers LP, Mouw TJ, Ferguson PJ, Wemmie JA, Mohapatra DP, Bassuk AG. The non-canonical Wnt ligand Wnt5a rescues morphological deficits in Prickle2-deficient hippocampal neurons. Mol Psychiatry. 2013 Oct;18(10):1049. PMID: 24056908. PMCID N/A

A role for Prickle genes in developmental pathways

In studies not anticipated by our original findings, we discovered that the Prickle genes likely influence multiple developmental pathways. Abnormalities in bone and palate in the C251X Prickle1 mutant mouse illuminated the role of Prickle1 in general developmental processes. These findings elucidate mechanism; and although we found Prickle1 dysfunction is coupled to Vangl abnormalities in bone development, it works independently of Vangl in palate formation, suggesting the Prickle pathway works differently in various developmental contexts. Our related studies of Prickle mutant mice showed Prickle2 mutants have ultrastructural motile ciliary abnormalities; Prickle1 mutants have abnormal facial branchiomotor motorneuron development; and the phenotypes of Prickle2 and Bbs7 mutants overlap via distinct mechanisms.

  • Sowers LP, Yin T, Mahajan VB, Bassuk AG. Defective motile cilia in Prickle2-deficient mice. J Neurogenet. 2014 Mar-Jun;28(1-2):146-52. PMID: 24708399. PMCID N/A
  • Yang T, Jia Z, Bryant-Pike W, Chandrasekhar A, Murray JC, Fritzsch B, Bassuk AG. Analysis of PRICKLE1 in human cleft palate and mouse development demonstrates rare and common variants involved in human malformations. Mol Genet Genomic Med. 2014 Mar;2(2):138-51. PMID: 24689077; PMCID: PMC3960056.
  • Mei X, Westfall TA, Zhang Q, Sheffield VC, Bassuk AG, Slusarski DC. Functional characterization of Prickle2 and BBS7 identify overlapping phenotypes yet distinct mechanisms. Dev Biol. 2014 Aug 15;392(2):245-55. PMID: 24938409; PMCID: PMC4114335.
  • Yang T, Bassuk AG, Stricker S, Fritzsch B. Prickle1 is necessary for the caudal migration of murine facial branchiomotor neurons. Cell Tissue Res. 2014 Sep;357(3):549-61. PMID: 24927917; PMCID: PMC4149827.

Identifying human neurodevelopment genes

We use a combination of neuroimaging expertise, expert clinical phenotyping and sample collection, massive parallel sequencing, proteomic analysis, and multiple animal model systems (including zebrafish, frog and dog) to identify genes involved in human neurodevelopmental defects.

  • Aldinger KA, Lehmann OJ, Hudgins L, Chizhikov VV, Bassuk AG, Ades LC, Krantz ID, Dobyns WB, Millen KJ. FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nat Genet. 2009 Sep;41(9):1037-42. PMID: 19668217; PMCID: PMC2843139.​
  • Safra N, Bassuk AG, Ferguson PJ, Aguilar M, Coulson RL, Thomas N, Hitchens PL, Dickinson PJ, Vernau KM, Wolf ZT, Bannasch DL. Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans. PLoS Genet. 2013;9(7):e1003646. PMID: 23874236; PMCID: PMC3715436.​
  • Bassuk AG, Muthuswamy LB, Boland R, Smith TL, Hulstrand AM, Northrup H, Hakeman M, Dierdorff JM, Yung CK, Long A, Brouillette RB, Au KS, Gurnett C, Houston DW, Cornell RA, Manak JR. Copy number variation analysis implicates the cell polarity gene glypican 5 as a human spina bifida candidate gene. Hum Mol Genet. 2013 Mar 15;22(6):1097-111. PMID:23223018 PMCID:PMC3578410.​
  • Darbro BW, Mahajan VB, Gakhar L, Skeie JM, Campbell E, Wu S, Bing X, Millen KJ, Dobyns WB, Kessler JA, Jalali A, Cremer J, Segre A, Manak JR, Aldinger KA, Suzuki S, Natsume N, Ono M, Hai HD, Viet le T, Loddo S, Valente EM, Bernardini L, Ghonge N, Ferguson PJ, Bassuk AG. Mutations in extracellular matrix genes NID1 and LAMC1 cause autosomal dominant Dandy-Walker malformation and occipital cephaloceles. Hum Mutat. 2013 Aug;34(8):1075-9.PMID:23674478 PMCID:PMC3714376

Retinal disease genes

Using techniques similar to those proposed in this application. I have worked with Dr.Mahajan to identify new causes and cures for retinal diseases. We found that Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy (ADNIV; a type of uveitis) can be caused by mutations in the cysteine protease CAPN5 (calpain-5), one member of a family of proteins that uses proteolysis to control a spectrum of molecular events. Together with Dr. Mahajan, we are building on this initial finding to discover novel mechanisms and treatments for uveitis.

  • Mahajan VB, Skeie JM, Bassuk AG, Fingert JH, Braun TA, Daggett HT, Folk JC, Sheffield VC, Stone EM. Calpain-5 mutations cause autoimmune uveitis, retinal neovascularization, and photoreceptor degeneration. PLoS Genet. 2012;8(10):e1003001. PMID: 23055945; PMCID: PMC3464205.
  • Wert KJ, Skeie JM, Bassuk AG, Olivier AK, Tsang SH, Mahajan VB. Functional validation of a human CAPN5 exome variant by lentiviral transduction into mouse retina. Hum Mol Genet. 2014 May 15;23(10):2665-77. PMID: 24381307; PMCID: PMC3990166.​
  • Bassuk AG, Yeh S, Wu S, Martin DF, Tsang SH, Gakhar L, Mahajan VB. Structural modeling of a novel CAPN5 mutation that causes uveitis and neovascular retinal detachment. PLoS One. 2015;10(4):e0122352. PMID: 25856303; PMCID: PMC4391918.
  • Wert KJ, Bassuk AG, Wu WH, Gakhar L, Coglan D, Mahajan M, Wu S, Yang J, Lin CS, Tsang SH, Mahajan VB. CAPN5 mutation in hereditary uveitis: the R243L mutation increases calpain catalytic activity and triggers intraocular inflammation in a mouse model. Hum Mol Genet. 2015 May 20;PubMed PMID: 25994508. PMCID: PMC4512628

Published works

My Bibliography

Ongoing research support

  • 1R01EY024665 (PI, Mahajan).


Structure and Function of Calpain-5

Role Co-investigator.


Gene Silencing and Gene Editing in Phototransduction

Role, MPI

  • 2R01AR059703-06A1 (MPI, Bassuk, Ferguson)


Genetic and Immunologic etiology of chronic recurrent multifocal osteomylitis (CRMO)

Role MPI​

  • 5R01EY026682 (MPI, Bassuk, Mahajan, Tsang)


Mechanistic Studies on Regenerative Medicine Approaches to Childhood Blindness

Role MPI, Contact PI

  • 5R01NS098590


Exploring Novel Epilepsy Pathways

Role. PI

  • NIH 5R01NS098590-03S1


Exploring Novel Epilepsy Pathways

Role: PI supervising Diversity Supplement for Lindsay Agostinelli

Completed research support

  • 1R01EY025225-01 (PI, MAHAJAN).


Mechanism-based therapies for photoreceptor degeneration

Role Co-investigator

  • CCOM Carver Medical Research Initiative


The Role of IL-1 in Traumatic Brain Injury Pathogenesis

Role PI


Evaluating GWAS AMD Candidate Loci by Gene Editing in Human iPS Cells

Role, MPI