Steven R. Van Doren, PhD

Professor

Biochemistry

Contact Information

Email VanDorenS@missouri.edu
Phone 573-884-6405
Address 37A Schweitzer Hall
Websites Van Doren Lab
TREND software
Google Scholar
CV Download PDF
Contact

Education

BS Biochemistry/Computer Science Oklahoma State University Stillwater, Okla.
PhD Biophysics University of Illinois Urbana-Champaign, Ill.

Research Areas

Structural biology: Biomolecular recognition, protein structure and dynamics by NMR, software to analyze NMR spectra and cardiac MRI

Research Description

Dynamic biological assemblies are strategic and fascinating. We have been exploring molecular recognition by flexible proteins and automatic tracking of changes in complex spectra and medical images.

Molecular recognition by proteins with intrinsic disorder

A pivotal virus-membrane interaction: Coronaviruses use a region of Spike to merge the viral envelope with the host cell membrane. We continue to be interested in the nature of the lipid interactions with this fusogenic region of Spike. Our articles reported (i) the NMR structure of the fusion peptide in a simple membrane-mimicking environment and (ii) its insertion and distortion of the simple membrane mimic via NMR-guided molecular dynamics simulations:

  • Koppisetti RK, Fulcher YG, Van Doren SR. The Fusion Peptide of SARS-CoV-2 Spike Rearranges into a Wedge Inserted in Bilayered Micelles. Am. Chem. Soc. 2021 Aug. 25. 143 (33) 13205–13211. https://doi.org/10.1021/jacs.1c05435
  • Van Doren SR, Scott BS, Koppisetti RK. SARS-CoV-2 Fusion Peptide Sculpting of a Membrane with Insertion of Charged and Polar Groups. Structure Sneak Peek: https://papers.ssrn.com/sol3/cf_dev/AbsByAuth.cfm?per_id=5632766 Accepted in principle on July 18, 2023
  • Supported by NSF award 2030473 with REU supplement, 2020-23, “RAPID: Structure of Membrane-Bound Fusion Peptide of SARS-CoV-2 Required for Infection”

Control point of biosynthesis of oils in chloroplasts: The making of plant oils, e.g. in soy and canola, begins with the highly regulated first step of fatty acid biosynthesis. This is the conversion of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase (ACCase). Some of the numerous subunits of the ACCase in chloroplasts may regulate the flow of carbon into oil biosynthesis. We are interested in the assembly of the subunits, their intrinsically disordered parts, and relevance to the regulation. We reported evidence of pH-sensing by BADC and BCCP subunits, with potential to regulate the biotin carboxylase activity during the daily light-dark cycle:

  • Ye Y, Fulcher YG, Sliman DJ 2nd, Day MT, Schroeder MJ, Koppisetti RK, Bates PD, Thelen JJ, Van Doren SR. (2020) The BADC and BCCP subunits of chloroplast acetyl-CoA carboxylase sense the pH changes of the light-dark cycle. J Biol Chem. 295(29), 9901-9916. https://www.jbc.org/content/295/29/9901.long

Other highly cited articles on mechanisms of protein-protein and protein-membrane interactions include:

  • Koppisetti R, Fulcher YG, Jurkevic A, Prior SH, Xu J, Lenoir M, Overduin M, and Van Doren SR. (2014) Ambidextrous Binding of Cell and Membrane Bilayers by Soluble Matrix Metallo-proteinase-12. Nature Commun. 5: 555
  • Van Doren, SR. (2015) Matrix metalloproteinase interactions with collagen and elastin. Matrix Biology 44-46:224-231.
  • Zhao Y, Marcink TM, Stawikowska R, Sanganna Gari RR, Marsh BP, King GM, Fields GB, Van Doren SR. (2015) Transient Collagen Triple Helix Binding to a Key Metalloproteinase in Invasion and Development. Structure 23(2):257-269.
  • Marcink TC, Simoncic JA, An B, Knapinska AM, Fulcher YG, Akkaladevi N, Fields GB, Van Doren SR. MT1-MMP Binds Membranes by Opposite Tips of its β-Propeller to Position it for Pericellular Proteolysis. Structure. 2019. 27(2):281-292.

Taking Signal Tracking to Heart

We developed an automatic way to resolve many kinds of change from series of complicated spectra or images, e.g., changes like ligand binding, protein unfolding, and heartbeat. We have developed software approaches that include applications to NMR-based drug screening, mitigation of breathing motion in free-breathing cardiac MRI, and characterization of irregular heartbeats in real-time MRI:

  • Xu J and Van Doren SR. Binding Isotherms and Time Courses Readily from Magnetic Resonance. Anal. Chem. 2016 Aug 16;88(16):8172-8.
  • Xu J and Van Doren SR. Tracking Equilibrium and Non-equilibrium Shifts in Data with TREND. Biophysical J. 2017 Jan 24; 112(2):224-233.
  • Namanja AT, Xu J, Wu H, Sun Q, Upahyay AK, Sun C, Van Doren SR*, Petros AM*. (2019) NMR-based Fragment Screening and Lead Discovery Accelerated by Principal Component Analysis. J. Biomol. NMR 73(12), 675-685.
  • Shammi AU, Luan Z, Xu J, Hamid A, Flors-Blasco L, Cassani J, Altes T, Thomen RP, Van Doren SR. Simplification of Free-Running Cardiac Magnetic Resonance by Respiratory Phase. medRxiv preprint (2022) https://medrxiv.org/cgi/content/short/2022.08.29.22279299v1
  • Recent support: American Heart Assn. 19IPLOI34760520, 2019-22, “Quantifying Cardiac Motion Abnormalities on MR Exams using Principal Component Analysis”

More information and software downloads are available at the TREND website at: https://trend.missouri.edu/

Notable Honors and Service

Selected Publications

Van Doren SR, Scott BS, Koppisetti RK. SARS-CoV-2 Fusion Peptide Sculpting of a Membrane with Insertion of Charged and Polar Groups. Structure 2023 Oct 5.31, 1-16. https://authors.elsevier.com/a/1heOA3SNvc6noU

Koppisetti RK, Fulcher YG, Van Doren SR. The Fusion Peptide of SARS-CoV-2 Spike Rearranges into a Wedge Inserted in Bilayered Micelles. J. Am. Chem. Soc. 2021 Aug. 25. 143 (33) 13205–13211. https://doi.org/10.1021/jacs.1c05435

Marcink TC, Simoncic JA, An B, Knapinska AM, Fulcher YG, Akkaladevi N, Fields GB, Van Doren SR. (2019). MT1-MMP Binds Membranes by Opposite Tips of Its β Propeller to Position It for Pericellular Proteolysis. Structure. 27(2):281-292.e6. doi: 10.1016/j.str.2018.10.008. [PubMed]

Xu J, Van Doren SR. (2018). Affinities and Comparisons of Enzyme States by Principal Component Analysis of NMR Spectra, Automated using TREND Software. Methods Enzymol. 607:217-240. doi: 10.1016/bs.mie.2018.05.016. [PubMed]

Van Doren SR. (2018). Domain Gymnastics of an ABC Transporter. Structure. 26(7):917-918. doi: 10.1016/j.str.2018.06.005. [PubMed]

Stiers KM, Xu J, Lee Y, Addison ZR, Van Doren SR, Beamer LJ. (2017). Phosphorylation-Dependent Effects on the Structural Flexibility of Phosphoglucosamine Mutase from Bacillus anthracis. ACS Omega. 2(11):8445-8452. doi: 10.1021/acsomega.7b01490. eCollection 2017 Nov 30. [PubMed]

Xu J, Sarma AVS, Wei Y, Beamer LJ, Van Doren SR. (2017). Multiple Ligand-Bound States of a Phosphohexomutase Revealed by Principal Component Analysis of NMR Peak Shifts. Sci Rep. 7(1):5343. doi: 10.1038/s41598-017-05557-w. [PubMed]

Fulcher YG, Prior SH, Masuko S, Li L, Pu D, Zhang F, Linhardt RJ, Van Doren SR. (2017). Glycan Activation of a Sheddase: Electrostatic Recognition between Heparin and proMMP-7. Structure. 25(7):1100-1110.e5. doi: 10.1016/j.str.2017.05.019. [PubMed]

Van Doren SR, Marcink TC, Koppisetti RK, Jurkevich A, Fulcher YG. (2017). Peripheral membrane associations of matrix metalloproteinases. Biochim Biophys Acta Mol Cell Res. 1864(11 Pt A):1964-1973. doi: 10.1016/j.bbamcr.2017.04.013. Review. [PubMed]

Marcink TC, Koppisetti RK, Fulcher YG, Van Doren SR. (2017). Mapping Lipid Bilayer Recognition Sites of Metalloproteinases and Other Prospective Peripheral Membrane Proteins. Methods Mol Biol. 1579:61-86. doi: 10.1007/978-1-4939-6863-3_5. [PubMed]

Xu J, Van Doren SR. (2017). Tracking Equilibrium and Nonequilibrium Shifts in Data with TREND. Biophys J. 112(2):224-233. doi: 10.1016/j.bpj.2016.12.018. [PubMed]

Fulcher YG, Fotso M, Chang CH, Rindt H, Reinero CR, Van Doren SR. (2016). Noninvasive Recognition and Biomarkers of Early Allergic Asthma in Cats Using Multivariate Statistical Analysis of NMR Spectra of Exhaled Breath Condensate. PLoS One. 11(10):e0164394. doi: 10.1371/journal.pone.0164394. eCollection 2016. [PubMed]

Xu J, Van Doren SR. (2016). Binding Isotherms and Time Courses Readily from Magnetic Resonance. Anal Chem. 88(16):8172-8. doi: 10.1021/acs.analchem.6b01918. [PubMed]

Prior SH, Byrne TS, Tokmina-Roszyk D, Fields GB, Van Doren SR. (2016). Path to Collagenolysis: COLLAGEN V TRIPLE-HELIX MODEL BOUND PRODUCTIVELY AND IN ENCOUNTERS BY MATRIX METALLOPROTEINASE-12. J Biol Chem. 291(15):7888-901. doi: 10.1074/jbc.M115.703124. [PubMed]

Prior SH, Fulcher YG, Koppisetti RK, Jurkevich A, Van Doren SR. (2015). Charge-Triggered Membrane Insertion of Matrix Metalloproteinase-7, Supporter of Innate Immunity and Tumors. Structure. 23(11):2099-110. doi: 10.1016/j.str.2015.08.013. [PubMed]

Zhao Y, Marcink TC, Sanganna Gari RR, Marsh BP, King GM, Stawikowska R, Fields GB, Van Doren SR. (2015). Transient collagen triple helix binding to a key metalloproteinase in invasion and development. Structure. 23(2):257-69. doi: 10.1016/j.str.2014.11.021. [PubMed]

Xu J, Lee Y, Beamer LJ, Van Doren SR. (2015). Phosphorylation in the catalytic cleft stabilizes and attracts domains of a phosphohexomutase. Biophys J. 108(2):325-37. doi: 10.1016/j.bpj.2014.12.003. [PubMed]

Van Doren SR. (2015). Matrix metalloproteinase interactions with collagen and elastin. Matrix Biol. 44-46:224-31. doi: 10.1016/j.matbio.2015.01.005. Review. [PubMed]

A mostly complete list of Van Doren’s publications can be found here.

Current Funding

NSF / MCB 1716688. A New Paradigm for Regulation of De Novo Fatty Acid Synthesis in Plants (Thelen, PI; Bates & Van Doren, coIs). 8/17 – 8/20

American Heart Association 19IPLOI34760520. Quantifying Cardiac Motion Abnormalities on MR Exams using Principal Component Analysis. (Van Doren, PI; Thomen, Flors Blasco, & Altes, coIs). 7/19 – 6/21

Hirshberg Foundation for Pancreatic Cancer Research. Early-Stage Drug Discovery Targeting a Marker of Pancreatic Cancer and its Metastasis. (Van Doren, PI; Brekken, co-I—UT Southwestern).

Coulter Translational Partnership at MU. HeartSpeed for Fast Cardiac MR Exams with Freedom to Breathe. (Van Doren, PI; Thomen & Altes, coIs). 7/18 – 6/20
MU Research Council URC-19-059. Early Stage Anti-Cancer Drug Screening: New Strategy to Block a Key Enzyme. 11/18 – 4/20


News Featuring Steven Van Doren