Boland Lab

Location and Contact Information

701 West 168th Street, 6-601
New York, NY 10032
United States

Principal Investigators

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

The Boland Lab 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 Institute of Genomic Medicine (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.

 

Lab Members

  • Gabriela De Almeida Sampaio

    Staff Associate

  • Andrew Ressler

    Graduate Student

    Andrew Ressler graduated from Brown University in 2013 with a Bachelor’s of Science in applied math-biology. He then worked at Amgen for two years as a finance associate before joining Columbia’s systems biology PhD program in 2015. As a PhD candidate in the Goldstein and Boland labs, Andrew is developing novel differentiation paradigms to study neurodevelopmental disorders in cultured human neural networks.

    Headshot of Andrew Ressler
  • Damian Williams

    Associate Research Scientist

    Damian has been studying neuronal function using electrophysiology and imaging techniques throughout his research career. For his doctorate in Tom Cunnane’s laboratory in the Department of Pharmacology at the University of Oxford, Damian studied neurotransmission in sympathetic neurons. Damian has used calcium imaging and electrophysiology to study neurotransmitter release at individual nerve terminal varicosities and nicotinic receptor-mediated modulation of sympathetic neurotransmitter release.

    After his DPhil, Damian joined Stephen Ikeda’s lab at NIAAA in Bethesda, Maryland. During this postdoctoral training, Damian studied the mechanisms involved in voltage-gated calcium channel modulation. Damian also developed a method for high-efficiency heterologous proteins expression in adult primary neurons, and a method for rapid modification of proteins in live cells using an inducible protease system.

    Damian continued his postdoctoral training in Amy MacDermott’s laboratory studying the physiological properties of stem cell-derived neurons. During this time and his position of managing the electrophysiology and calcium imaging section of the Columbia Stem Cell Core, Damian has gained extensive experience of stem cell-derived tissues. He has been central to projects which span across the field, including the characterization of stem cell lines, understanding the mechanisms of neuronal development and disease, and the development of drug screening platforms for ALS and neuromuscular disease.

    Research Overview

    The aim of Damian’s research is to understand functional changes in neurons that occur in epilepsy and intellectual disability. Using a variety of electrophysiological and image-based techniques, Damian can identify changes at molecular, individual neuron, and synaptic levels. This work is carried out with the Boland, Goldstein, and Frankel laboratories, using murine and stem cell-based models that harbor disease-causing genetic variants identified at the Institute of Genomic Medicine (IGM). Insight into the mechanism of changes to neuron function will provide novel drug targets to specific biological processes, which has the potential to improve treatment of previously intractable disease.

    Headshot of Damian Williams

Select 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

  • Boland MJ, Goldstein DB, Frankel WN, Amador A, Bostick CD, Olson H, Peters J, Camp CR, Krizay D, Chen W, Han W, Tang W, Kanber A, Kim S, Teoh J, Sah M, Petri S, Paek H, Kim A, Lutz CM, Yang M, Myers SJ, Bhattacharya S, Yuan H, Poduri A, Traynelis SF (2020) Modelling and treating GRIN2A developmental and epileptic encephalopathy in mice. Brain, Volume 143, Issue 7, July 2020, Pages 2039–2057. https://academic.oup.com/brain/article-abstract/143/7/2039/5861741