Makinson Lab
Location and Contact Information
Principal Investigator
The Makinson lab takes a multi-modal approach to understand the complex relationships between early developmental genetic impairments and evolving disease phenotypes. Using genome engineering, we introduce clinically-relevant variants into mice and human induced pluripotent stem cells (hiPSC) to generate rodent and human brain organoid models of neurological and neuropsychiatric disease. We then use these rodent and human models to probe the resulting molecular and neurophysiological impairments that result. From these studies we design targeted manipulations to identify the most relevant points of impairment, potential targets for therapeutic interventions, and often in the process we uncover unexpected roles of these genes in normal/typical brain development.
One area of particular interest for our lab is epilepsy which is a devastating neurological disorder that is characterized by the occurrence of spontaneous seizures. Seizures, which fundamentally reflect hyperexcitability in neural networks, manifest at the cellular, simple microcircuit, and the systems level and are captured well by diverse model systems. This allows us to probe the consequences of epilepsy-related variants at multiple levels of complexity and to make comparisons across rodent and human cell model systems. This paradigm enables us to uncover the most fundamental aspects of a given gene's functions in shaping brain activity, its role in pathogenesis, and its place within the larger, often complex, genetic risk architecture.
We are committed to supporting creative independent thinkers of all backgrounds to do their best work towards making impactful contributions to basic and translational neuroscience. Interested students or trainees are encouraged to reach out to Dr. Makinson to inquire about open positions in the lab.
Lab Members
Damian Williams, PhD
- Associate Research Scientist
Damian began his research career at the University of Oxford where he obtained his doctorate studying how nicotinic receptors regulate neurotransmission in sympathetic nerves. Damian then moved to the US to carry out postdoctoral training at NIH and Columbia University. During this period, he investigated the mechanisms by which voltage gated calcium channels are regulated before moving into the neurological disease field studying ALS using iPSC-derived motor neurons. Following this, Damian led the Electrophysiology and Calcium Imaging Section of Columbia University Stem Cell Core. Damian joined the Makinson lab in 2017 where he has characterized the excitability and synaptic changes in a number of epilepsy models. Damian is particularly interested in axon function in normal and diseased states.
Jane Simko, PhD
- Postdoctoral Fellow
Jane studied at UC Berkeley for her undergraduate degree then pursued a masters and doctorate in Neuroscience at the University of Lausanne and École Polytechnique Fédérale de Lausanne in Switzerland. Her thesis under the direction of Prof. Henry Markram involved studying the morphology and functionality of local interneurons in the thalamus of mice using multiple patch clamp electrophysiology. She is now a Postdoctoral Fellow in the Makinson lab working to understand the role of local interneurons in the thalamus in sensory processing and epilepsy.
Erin Cullen, PhD
- Postdoctoral Fellow
Erin received her undergraduate degree from University of Pittsburgh. She completed her PhD at University of Vermont under the direction of Dr. Matthew Weston. Her thesis research focused on defining the role of the two mTOR complexes in genetic epilepsies that act through the mTOR pathway. She continues to pursue epilepsy research as a postdoc in the Makinson lab, where she utilizes patch clamp electrophysiology and two-photon calcium imaging to study mechanisms of neural dysfunction in sodium channelopathies.
Christine Liu
- Graduate Student Neurobiology & Behavior PhD Program
Christine is a PhD student in the Neurobiology and Behavior program at Columbia University. She completed her undergraduate studies in Computer Science and Electrical Engineering at Stanford University in 2021, while working in the labs of Dr. John Huguenard and Dr. Surya Ganguli on seizure prediction models with machine learning. Currently, she is developing machine learning assisted approaches to seizure detection and classification and helping to build the next generation of human brain organoid models of epilepsy.
Jack Whitely
- Graduate Student Neurobiology & Behavior PhD Program
Jack is a PhD student in the Neurobiology and Behavior program at Columbia University. As an undergraduate student at the University of California, San Diego (UCSD), he worked as a Lab Technician and Research Assistant in the Fred H. Gage lab at the Salk Institute for Biological Studies under Dr. Tomohisa Toda, Dr. Maria C. Marchetto, and Dr. Jeff Jones. Here, he used stem cell-based models to study neuropsychiatric risk loci and mouse models to better understand how transposable elements play a role in neurodevelopment. In the Makinson lab he will leverage stem cell-derived brain organoids to study genetic epilepsies and the circuit mechanisms of rhythm generation in assembled circuits.
Kyle Helms
- Graduate Student Integrated Program in Cellular, Molecular, and Biomedical Studies
Kyle is a PhD student in the Integrated Program of Cellular, Molecular, and Biomedical Studies at Columbia. He’s coming directly from his undergraduate studies in Biology at New Mexico State University. As an undergraduate MARC Fellow under direction of Dr. Jennifer Curtiss, he used fruit flies as a model to study transcriptional regulation and protein interactions during development. Before coming to NYC, he spent a virtual summer at UCSF developing computational approaches to analyze archaeal replication under direction of Prof. Carol Gross. At Columbia, he is excited to bring his genetics and molecular biology background to the Makinson lab’s endeavor to study neurodevelopmental consequences of voltage-gated sodium channels in health and disease.
Tamina (Keira) Ramirez
- Graduate Student Neurobiology & Behavior PhD Program
Keira is currently pursuing her PhD in the Neurobiology and Behavior program at Columbia University. Keira began her research endeavors in 2012 at Seattle Children’s Research Institute, studying the effect of sensory overstimulation on development. This exploration continued throughout her undergraduate years at Western Washington University. In 2014, Keira embarked on an internship at the University of Washington, collaborating with Dr. Franck Kalume to unravel the pathophysiology of genetic epilepsy using an SCN1A knockout mouse model of Dravet Syndrome. Upon earning her B.S. in Behavioral Neuroscience, Keira transitioned to the Allen Institute for Brain Science. There, she investigated the functional connectivity of the visual system employing high-density Neuropixels probes. Now, she eagerly brings her expertise in electrophysiology, surgery, and mouse neurocircuitry to the Makinson Lab. Her research focuses on examining the role of local interneurons in fundamental thalamic functions and their integration within the thalamocortical circuit, particularly in relation to seizure generation and termination in an SCN8A mouse model of epilepsy.
Büse Özel
- Research Staff Associate
Büse majored in Molecular Biology and Genetics at Middle East Technical University (METU) before completing a Masters degre in Cancer Biology at Bilkent University in Turkey. Buse studied early stages of human development under the supervision of Prof. Austin Smith at the University of Cambridge. While at Cambridge she investigated regulatory networks governing trophectoderm segregation in naive state embryonic stem cells. Buse is now a Staff Associate in the Makinson lab working on 3D-cell culture models of epilepsy derived from human pluripotent stem cells.
Caryn Martin
- Research Technician
Caryn graduated in 2021 from the University at Albany with a BS in Biology and a Minor in Neuroscience. During her undergraduate studies, she spent time working in Dr. Damian Shin’s lab at Albany Medical Center studying the viability of cells and neurons in adult parkinsonian rats. Caryn is now a Research Technician in the Makinson Lab managing administrative, molecular, surgical, and animal support for the lab.
Select Publications
Elleman, A.V., Milicil N., Williams D.J., Simko J., Liu J.C., Haynes A.L., Ehrlich D.E.*, Makinson C.D.*, Du Bois J.*, Behavioral control through the direct, focal silencing of neuronal activity. Cell Chemical Biology (2024).
Evans SW, Shi DQ, Chavarha M, Plitt MH, Taxidis J, Madruga B, Fan JL, Hwang FJ, van Keulen SC, Suomivuori CM, Pang MM, Su S, Lee S, Hao YA, Zhang G, Jiang D, Pradhan L, Roth RH, Liu Y, Dorian CC, Reese AL, Negrean A, Losonczy A, Makinson CD, Wang S, Clandinin TR, Dror RO, Ding JB, Ji N, Golshani P, Giocomo LM, Bi GQ, Lin MZ. A positively tuned voltage indicator for extended electrical recordings in the brain. Nature Methods, 1104-1113 (2023).
Colombo S, Reddy HP, Petri S, Williams DJ, Shalomov B, Dhindsa RS, Gelfman S, Krizay D, Bera AK, Yang M, Peng Y, Makinson CD, Boland MJ, Frankel WN, Goldstein DB, Dascal N. Epilepsy in a mouse model of GNB1 encephalopathy arises from altered potassium (GIRK) channel signaling and is alleviated by a GIRK inhibitor. Frontiers in Cellular Neuroscience, 18;17:1175895 (2023).
Teng, S., Zhen F., Wang L., Schalchli J.C., Simko J., Chen X., Jin H., Makinson, C.D., Peng Y., Control of non-REM sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area. Nature Communications, 12;13(1):4748 (2022)
Elleman, A.V., Devienne G.D., Makinson, C.D., Haynes A.L., Huguenard, J.R., Du Bois J., Precise spatiotemporal control of voltage-gated sodium channels by photocaged saxitoxin. Nature Communications, 7;12(1):4171 (2021).
Gordon, A., Yoon, S., Tran S.S., Makinson, C.D., Park Y.J., Andersen, J., Valencia, A.M., Horvath, S., Xiao, X., Huguenard, J.R., Pasca, S.P., Geschwind, D.H., Long term maturation of human cortical organoids matches key early postnatal transitions. Nature Neuroscience, (2021).
Wong, J.C., Makinson, C.D., Lamar, T., Cheng, Q., Wingard, J.C., Terwilliger, E.F., Escayg, A. Selective targeting of Scn8a prevents seizure development in a mouse model of mesial temporal lobe epilepsy. Scientific Reports, 8:126 (2018).
Birey, F.*, Andersen, J.*, Makinson, C.D.*, Islam, S., Wei, W., Huber, N., Fan, H.C., Metzler, K.R.C., Panagiotakos, G., Thom, N., O'Rourke, N.A., Steinmetz, L.M., Bernstein, J.A., Hallmayer, J., Huguenard, J.R. & Pasca, S.P. Assembly of functionally integrated human forebrain spheroids. Nature, 545:54-59 (2017).
Makinson, C.D., Tanaka, B.S., Sorokin, J.M., Wong, J.C., Christian, C.A., Goldin, A.L., Escayg, A. & Huguenard, J.R. Regulation of thalamic and cortical network synchrony by Scn8a. Neuron, 93:1165-1179 (2017).
Makinson, C.D., Dutt, K., Lin, F., Papale, L.A., Shankar, A., Barela, A.J., Liu, R., Goldin, A.L. & Escayg, A. An Scn1a epilepsy mutation in Scn8a alters seizure susceptibility and behavior. Experimental Neurology, 275 Pt 1:46-58 (2016).
Pasca, A.M., Sloan, S.A., Clarke, L.E., Tian, Y., Makinson, C.D., Huber, N., Kim, C.H., Park, J.Y., O'Rourke, N.A., Nguyen, K.D., Smith, S.J., Huguenard, J.R., Geschwind, D.H., Barres, B.A. & Pasca, S.P. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nature Methods, 12:671-678 (2015).
Makinson, C.D. & Huguenard, J.R. Attentional flexibility in the thalamus: Now we're getting SOMwhere. Nature Neuroscience, 18:2-4 (2015).
Makinson, C.D.*, Tanaka, B.S.*, Lamar, T., Goldin, A.L. & Escayg, A. Role of the hippocampus in Nav1.6 (Scn8a) mediated seizure resistance. Neurobiology of Disease, 68:16-25 (2014).