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Bryan W. Luikart, PhD

Associate Professor of Molecular and Systems Biology

Molecular and Systems Biology

1999 B.S., Molecular and Cell Biology (Summa Cum Laude), Texas A&M University, College Station, Texas

2004 Ph.D., Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas (Luis F. Parada, mentor)

Neuroscience Center at Dartmouth
Program in Experimental and Molecular Medicine


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Contact Information

Bryan W. Luikart
Vail 604
74 College Street
Hanover NH 03755

Office: 603-650-1633
Phone: 603-650-1643

Professional Interests

The Impact of Pten Dysfunction on Neuronal Physiology - a Model for Autism
Autism Spectrum Disorder (ASD) is a developmental disorder characterized by symptoms such as altered social interaction, restricted communication, and stereotyped behavior. ASD represents a broad class of disorders that have common features, but no single genetic defect is responsible for all forms of ASD. An example of a genetic defect that may cause some forms of ASD is mutations in the gene Pten. Mutations in Pten have been in 5 to 17% of patients with ASD and an enlarged head (macrocephaly). Deletion of Pten in the mouse brain also causes macrocephaly and deficits in social behavior, suggesting that abnormal Pten signaling in neurons may cause this type of ASD. We are currently investigating the functional impact of specific autism-related mutations of Pten on neuronal form and function. We are also examining other genes that may interact with Pten to alter neuronal physiology and synapse formation. We use both in vitro models and in vivo molecular manipulation with viral vectors, whole-cell electrophysiology, and advanced microscopy to test directed hypotheses. Understanding the primary effects of Pten mutations on the function of individual neurons will improve our understanding of the dysfunctional autistic brain. Further, establishing that manipulation of Pten in the mouse can mimic the symptoms of human ASD patients will allow scientists to test treatments that could cure certain forms of ASD.

Cytoskeletal regulation in neuronal development
Autism is clearly a spectrum of disorders in which around half of the cases are associated with a specific genetic mutation. However, no more than 2% of all cases are caused by any one mutation. Autism-associated mutations modeled in the mouse brain cause defects in morphological development and synaptic connectivity of neurons. Thus, regulation of neuronal growth and sculpting of synaptic connectivity may underly the development of cognitive and affective behaviors that are altered in autism. We know that growth factors and related signaling pathways modulate neuronal growth through the regulation of translation and cytoskeletal remodeling. While we have learned a great deal about these pathways and the regulation of translation through the context of autism research, the dysregulation of cytoskeletal dynamics in the context of autism is largely unexplored. In this project we have used a bioinformatic approach to predict whether gene mutations found in patients with autism will directly regulate cytoskeletal proteins. We are now using our retroviral CRISPR system to examine the morphological impact of the genes that likely impact the cytoskeleton. For genes having an impact in this somatic cell screen, we are implementing CRISPR in mouse zygotes to generate novel whole-animal models for autism.

Rotations and Thesis Projects

Rotations can be tailored to the interest of specific students. We commonly use whole-cell electrophysiology, molecular cloning to produce novel viral vectors, in vivo viral injections, histology and advanced microscopy to study the topics described above.

Grant Information

NIMH R01 “The Impact of Pten Signaling on Neuronal Form and Function” (R01MH097949-01)

Courses Taught

Neurogenetics, Neural Circuits and Plasticity; Course in Experimental Molecular Medicine (PEMM101)
Autism Spectrum Disorder; Neurobiology of Disease (PEMM 211)
Endocrinology Lecturer and Small Group Leader; Medical Physiology (PHSL120)
Molecular Neuroscience; Neuroscience II (PEMM 212)
Neurotrophins and Neuronal Morphology; Advanced Biomedical Physiology (PEMM 271)

Selected Publications


TCF4 Mutations Disrupt Synaptic Function Through Dysregulation of RIMBP2 in Patient-Derived Cortical Neurons.
Davis BA, Chen HY, Ye Z, Ostlund I, Tippani M, Das D, Sripathy SR, Wang Y, Martin JM, Shim G, Panchwagh NM, Moses RL, Farinelli F, Bohlen JF, Li M, Luikart BW, Jaffe AE, Maher BJ
Biol Psychiatry. 2023 Aug 10; pii: S0006-3223(23)01488-9. doi: 10.1016/j.biopsych.2023.07.021. Epub 2023 Aug 10.
PMID: 37573005

Toward a better understanding of PHTS heterogeneity: commentary on 'Cell-type specific deficits in PTEN-mutant cortical organoids converge on abnormal circuit activity'.
Tan Z, Luikart BW
Hum Mol Genet. 2023 Sep 5;32(18):2771-2772. doi: 10.1093/hmg/ddad127.
PMID: 37540221

Single-cell analysis of the nervous system at small and large scales with instant partitions.
Frazel PW, Fricano-Kugler K, May-Zhang AA, O'Dea MR, Prakash P, Desmet NM, Lee H, Meltzer RH, Fontanez KM, Hettige P, Agam Y, Lithwick-Yanai G, Lipson D, Luikart BW, Dasen JD, Liddelow SA
bioRxiv. 2023 Jul 18; pii: 2023.07.14.549051. doi: 10.1101/2023.07.14.549051. Epub 2023 Jul 18.
PMID: 37503160

TCF4 mutations disrupt synaptic function through dysregulation of RIMBP2 in patient-derived cortical neurons.
Davis BA, Chen HY, Ye Z, Ostlund I, Tippani M, Das D, Sripathy SR, Wang Y, Martin JM, Shim G, Panchwagh NM, Moses RL, Farinelli F, Bohlen JF, Li M, Luikart BW, Jaffe AE, Maher BJ
bioRxiv. 2023 Jan 20; pii: 2023.01.19.524788. doi: 10.1101/2023.01.19.524788. Epub 2023 Jan 20.
PMID: 36712024

Adult-born neurons inhibit developmentally-born neurons during spatial learning.
Ash AM, Regele-Blasco E, Seib DR, Chahley E, Skelton PD, Luikart BW, Snyder JS
Neurobiol Learn Mem. 2023 Feb;198:107710. doi: 10.1016/j.nlm.2022.107710. Epub 2022 Dec 23.
PMID: 36572174

mTORC2 Inhibition Improves Morphological Effects of PTEN Loss, But Does Not Correct Synaptic Dysfunction or Prevent Seizures.
Cullen ER, Tariq K, Shore AN, Luikart BW, Weston MC
J Neurosci. 2023 Feb 1;43(5):827-845. doi: 10.1523/JNEUROSCI.1354-22.2022. Epub 2022 Dec 16.
PMID: 36526374

Disruption of mTORC1 rescues neuronal overgrowth and synapse function dysregulated by Pten loss.
Tariq K, Cullen E, Getz SA, Conching AKS, Goyette AR, Prina ML, Wang W, Li M, Weston MC, Luikart BW
Cell Rep. 2022 Nov 1;41(5):111574. doi: 10.1016/j.celrep.2022.111574.
PMID: 36323257

Pten heterozygosity restores neuronal morphology in fragile X syndrome mice.
Sathyanarayana SH, Saunders JA, Slaughter J, Tariq K, Chakrabarti R, Sadanandappa MK, Luikart BW, Bosco G
Proc Natl Acad Sci U S A. 2022 Apr 12;119(15):e2109448119. doi: 10.1073/pnas.2109448119. Epub 2022 Apr 8.
PMID: 35394871

PTEN Regulates Dendritic Arborization by Decreasing Microtubule Polymerization Rate.
Getz SA, Tariq K, Marchand DH, Dickson CR, Howe Vi JR, Skelton PD, Wang W, Li M, Barry JM, Hong J, Luikart BW
J Neurosci. 2022 Mar 9;42(10):1945-1957. doi: 10.1523/JNEUROSCI.1835-21.2022. Epub 2022 Jan 31.
PMID: 35101965

Striking a balance: PIP(2) and PIP(3) signaling in neuronal health and disease.
Tariq K, Luikart BW
Explor Neuroprotective Ther. 2021;1:86-100. doi: 10.37349/ent.2021.00008. Epub 2021 Oct 29.
PMID: 35098253

View more publications on PubMed