Michael Boland

Profile Headshot

Overview

Academic Appointments

  • Assistant Professor of Molecular Sciences (in Neurology and the Institute of Genomic Medicine) at CUMC

Administrative Titles

  • Director, Cellular Models of Disease – Institute for Genomic Medicine

Gender

  • Male

Credentials & Experience

Education & Training

  • BS, Biotechnology, University of Nebraska
  • PhD, Biochemistry & Molecular Biology, University of Nebraska Medical Center

Research

My group applies an integrated developmental and functional approach to model neurological disorders using human induced pluripotent stem cells (hiPSCs), with a primary focus on epilepsy and monogenic autism spectrum disorders. Disease-causing gene variants identified by human genetics studies conducted at the IGM serve as the basis for model development within my group. Our hiPSC models and differentiation schemes are tailored to the gene being studied. We generate patient-derived hiPSC lines and use genomic editing via CRISPR/Cas9 to correct the mutation. Alternatively, a given pathogenic mutation will be edited into the genome of a validated, non-disease hiPSC line in order to match patient genotypes. Depending on the disease/mutation studied, we use monolayer and/or three-dimensional (organoid) neuronal differentiation of hiPSCs into clinically-relevant cell types coupled with morphological studies, and transcriptomic and gene network analyses to identify and understand genotype-specific developmental phenotypes. Additionally, we have developed and advanced the use of patch clamp electrophysiology and multielectrode arrays combined with optogenetic and pharmacological network modulation to understand the functional etiology of these disorders.

In collaboration with other investigators at the IGM, we study microcircuit and neural network behavior of cultured primary neurons and acute brain slices from genetic mouse models of epilepsy for preclinical drug design and development.

Selected Publications

Gelfman S, Wang Q, McSweeney KM, Ren Z, La Carpia F, Halvorsen M, Schoch K, Ratzon F, Heinzen EL, Boland MJ, Petrovski S, Goldstein DB. (2017) Annotating pathogenic variants in non-coding regions. Nat. Commun. 8: 236-247 doi: 10.1038/s41467-017-00141-2.

Boland MJ*, Nazor KL*,Tran HT, Szucs A, Lynch CL, Paredes R, Tassone F, Sanna PP, Hagerman RJ, Loring JF. (2017) Molecular analyses of neurogenic defects in a human pluripotent stem cell model of Fragile X Syndrome. Brain. 140(3):582-598 doi: 10.1093/brain/aww357. *these authors contributed equally.

McSweeney KM, Gussow AB, Bradrick SS, Dugger SA, Gelfman S, Wang Q, Petrovski S, Frankel WN, Boland MJ, Goldstein DG. (2016) Inhibition of microRNA-128 promotes excitability of cultured cortical neuronal networks. Genome Research.26:1411-1416

Hazen JL*, Faust G*, Rodriguez AR, Ferguson W, Shumilina S, Clark RA, Boland MJ, Martin G, Chubukov P, Tsunemoto RK, Torkamani A, Kupriyanov S, Hall IA, Baldwin KK. (2016) The complete genome sequences, unique mutational spectra and developmental potency of adult neurons revealed by cloning. Neuron. 89:1223-1236

Nazor KL, Boland MJ, Bibikova M, Klotzle B, Yu M, Glenn-Pratola VL, Schell JP, Coleman RL, Cabral-da-Silva MC, Schmidt U, Peterson SE, He C, Loring JF, Fan J-B. (2014) Application of a low-cost array-based technique - TAB-Array - for quantifying and mapping both 5mC and 5hmC at single-base resolution in human pluripotent stem cells. Genomics. 104: 358-367

Boland MJ, Nazor KL, Loring JF. (2014) Epigenetic regulation of pluripotency and differentiation. Circulation Res. 115:311-324.

Quinlan AR*, Boland MJ*, Leibowitz ML, Shumilina S, Pehrson SM, Baldwin KK, Hall IM. (2011) Paired-end DNA sequencing of mouse induced pluripotent stem cell genomes reveals rare mutations and retroelement stability. Cell Stem Cell. 9: 366-373 doi: 10.1016/j.stem.2011.07.018. *these authors contributed equally.

Boland MJ*, Hazen JL*, Nazor KL*, Rodriquez AR, Gifford W, Martin G, Kupriyanov S, Baldwin KK. (2009) Adult mice generated from induced pluripotent stem cells. Nature. 46: 91-96 *these authors contributed equally.

Boland MJ and Christman JK. (2008) Characterization of Dnmt3b:thymine-DNA glycosylase interaction and stimulation of thymine glycosylase-mediated repair by DNA methyltransferase(s) and RNA. J. Mol. Biol. 379(3): 492-504