Research Interests

My overarching research goal is to understand how ion channels regulate vital physiological processes by elucidating their structure-function inter-relationship. Recently, we achieved a 4.7 Å resolution structure of the Ca2+ release channel IP3R and filled a significant knowledge gap for how native Ca2+ channel gating machinery is assembled in the full-length tetrameric structure in the absence of channel regulators. IP3Rs are masterful signal integrators, with over 100 regulatory molecules/proteins, that can finely tune cell Ca2+ concentrations to achieve precise conditions to control learning and memory, fertilization, gene transcription, etc., and channel dis-regulation is connected to many human health impacts including cancer, cardiovascular and neurodegenerative diseases. My work is committed to answering key questions regarding how Ca2+ channels process complex regulatory signals, and how these signals affect channel gating on a structural basis in normal and disease conditions. Our research strategy utilizes successfully implemented multidisciplinary methods that include biochemical and biophysical characterization, single-particle electron cryomicroscopy (cryo-EM), computational methods, molecular modeling and bioinformatics to define the molecular interactions regulating IP3R function. With this approach we are now well positioned to achieve atomic resolution structural information of IP3R in different functional states, which is key to understanding channel function in Ca2+ signaling and Ca2+ channel related diseases.

Publications

  • Baker MR, Fan G, Serysheva II. Structure of IP3R channel: high-resolution insights from cryo-EM. Curr Opin Struct Biol. 2017 Jun 12;46:38-47. doi: 10.1016/j.sbi.2017.05.014. Link
  • Fan G, Baker ML, Wang, Z, Baker MR, Sinyagovskiy PA, Chiu W, Ludtke SJ and Serysheva II. Gating Machinery of IP3R Channels Revealed by Electron Cryo-Microscopy. Nature 2015 Nov 19;527(7578):336-41. Link
  • Baker MR, Fan G, Serysheva II. Single-particle cryo-EM of the ryanodine receptor channel in an aqueous environment. Eur J Transl Myol. 2015;25(1):35-48. Link
  • Popova OB, Baker MR, Tran TP, Le T, Serysheva II. Identification of ATP-Binding Regions in the RyR1 Ca2+ Release Channel. PLoS One. 2012 Nov;7(11), PMC3492408. Link
  • Baker MR, Rees I, Ludtke SJ, Chiu W, Baker ML. Constructing and Validating Initial Cα Models from Subnanometer Resolution Density Maps with Pathwalker. Structure. 2012 Mar 7;20(3):450-63, PMC3307788. Link
  • Baker, ML, Baker MR, Hryc C, Ju T, Chiu W. Gorgon and Pathwalking: Macromolecular Modeling Tools for Subnanometer Resolution Density Maps. Biopolymers. 2012 Sep;97(9):655-68. Link
  • Baker ML, Baker MR, Cong Y. Computational methods for interpretation of EM maps at subnanometer resolution. 2012 Jan, In: eLS. John Wiley & Sons Ltd, Chichester. Link
  • Baker, ML, Baker, MR, Hryc, CF, and DiMaio, F. Analyses of Subnanometer Resolution Cryo-EM Density Maps. Methods in Enzymology. 2010 May; 483:1-29, PMC3107677. Link
  • Fallon J*, Baker MR*, Xiong L*, Loy RE, Yang G, Dirksen RT, Hamilton SL, Quiocho FA. Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca2+·calmodulins. Proc Natl Acad Sci U S A. 2009 Mar;106(13):5135–5140, PMC2654391. Link
  • Durham WJ, Aracena-Parks P, Long C, Goonasekera SA, Boncompagni S, Gilman CP,Galvan DL, Rossi AE, Baker MR, Shirokova N, Protasi F, Dirksen RT, Hamilton SL. RyR1 S-nitrosylation underlies Environmental Heat Stroke and Sudden Death in Y522S RyR1 Knock-in mice. Cell. 2008 April;133(1):53–65, PMC2366094. Link
  • Serysheva II, Ludtke SJ, Baker MR, Chiu W, Hamilton SL. Structure of the voltage-gated L-type Ca2+ channel by electron cryomicroscopy. Proc Natl Acad Sci. 2002 Aug;99(16):10370-5, PMC124921. Link
  • Lalani SR, Ware SM, Wang X, Zapata G, Tian Q, Franco LM, Jiang Z, Bucasas K, Scott DA, Campeau PM, Hanchard N, Umaña L, Cast A, Patel A, Cheung SW, McBride KL, Bray M, Craig Chinault A, Boggs BA, Huang M, Baker MR, Hamilton S, Towbin J, Jefferies JL, Fernbach SD, Potocki L, Belmont JW. MCTP2 is a dosage-sensitive gene required for cardiac outflow tract development. Hum Mol Genet. 2013 Jun 27. PMID: 23773997. Link

Education

Post-doctoral Fellow at UTHSC - Department of Biochemistry and Molecular Biology, Advisor: Irina Serysheva, 2012-present

NLM Bioinformatics Post-doctoral Fellow at Baylor College of Medicine - National Center for Macromolecular Imaging, Advisor: Wah Chiu, 2009-2012

Ph.D., Baylor College of Medicine - Structural and Computational Biology and Molecular Biophysics, Advisor: Susan Hamilton, 2009

© Copyright 2008-Present - The University of Texas Health Science Center at Houston (UTHealth)