Marcos Otero-Garcia, PhD

Profile Headshot

Overview

Changes in brain tissue architecture are fundamental to aging and disease. These intricated spatial patterns have limited our ability to decipher neurodegenerative processes. However, recent advances in single-cell and spatial omics methods present an opportunity to leap our understanding of the mechanisms behind neurodegenerative disease progression.

I am deeply interested in technological innovation and neurodegenerative diseases, particularly the development of spatial omics methods to study proteinopathies. During my postdoctoral training at UCLA and Stanford, we designed novel methods for unbiased single-cell probing of human brain tissue. Our approach revealed specific neuronal cell types susceptible to neurofibrillary tangles and the associated molecular signatures in Alzheimer’s Disease patients. However, single-cell sequencing protocols compromise the spatial context. By combining high-throughput molecular profiling with high-resolution imaging, we created spatial omics technologies capable of interrogating hundreds of targets in intact tissue sections. We applied them to the study of brain development and demyelination in both human samples and animal models.

I am currently focused on implementing and developing new spatial methods to map the cellular and molecular heterogeneity of the human brain during healthy aging and neurodegenerative disorders. My goal is to create innovative tools and valuable datasets to enhance our understanding of neurodegenerative processes, identify therapeutic targets, and improve human health.

Administrative Titles

  • Senior Research Scientist

Gender

  • Male

Credentials & Experience

Education & Training

  • UD, 2008 Biology & Biochemistry, University of Valencia
  • MS, 2010 Neuroscience, University of Valencia
  • PhD, 2015 Neuroscience, University of Valencia

Research

Selected Publications

  1. Otero-Garcia M, Mahajani SU., Wakhloo D., Tang W., Xue YQ., Morabito S., Pan J., Oberhauser J., Madira AE., Shakouri T., Deng Y., Allison T., He Z., Lowry WE., Kawaguchi R., Swarup V, Cobos I. Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer’s disease. Neuron, June 2022. 10.1016/j.neuron.2022.06.021
  2. Pandey S., Shen K., Lee SH., Shen YA., Wang Y., Otero-Garcia M., Vito S., Laufer B., Newton D., Rezzonico D., Hanson J., Kaminker JS., Bohlen C., Yuen TJ., Friedman BA. Disease-associated Oligodendrocyte Responses Across Neurodegenerative Diseases. Cell Reports, May 2022. 10.1016/j.celrep.2022.111189
  3. Farrell K, Kim SH, Han N, Iida MA, Gonzalez E, Otero-Garcia M, …, Cairns NJ, Franklin EE, Cohen HT, Raj T, Cobos I, Bess Frost B, Goate A, White III CL, Crary JF. Genome-wide association study and functional validation implicates JADE1 in tauopathy. Acta Neuropathologica, January 2022. 10.1007/s00401-021-02379-z
  4. Allison T, Langerman J, Sabri S, Otero-Garcia M, Lund A, Huang J, Wei X, Samarsinghe R, Pouladakis D, Mody I, Cobos I, Novitch B, Geschwind D, Plath K, Lowry WE. Defining the nature of human pluripotent stem cell-derived interneurons via single cell analysis. Stem Cell Reports, September 2021. 10.1016/j.stemcr.2021.08.006
  5. Bhaduri A.; Sandoval-Espinosa C.; Otero-Garcia M.; Oh I.; Yin R.; Eze U.C.; Nowakowski T.J.; Kriegstein A.R. An Atlas of Arealization Identifies Dynamic Molecular Signatures in the Developing Human Brain. Nature, Oct 2021. 10.1038/s41586-021-03910-8