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Thomas Cleveland (Fed)

Physicist

Staff Bio

Thomas received his Ph.D. in 2014 from the Johns Hopkins School of Medicine, Program in Molecular Biophysics, in the laboratory of Prof. Daniel Leahy. During his Ph.D., he performed structural and biochemical studies on extracellular components of the Hedgehog signaling pathway, as well as biochemical studies of the EGFR/HER/ErbB family of receptors. He then joined the NIST Center for Neutron Research as a National Research Council (NRC) postdoctoral fellow in 2014, where he worked under Paul Butler and Susan Krueger. In his postdoctoral work, he used Small-Angle X-ray and Neutron Scattering (SAXS/SANS) to study the process of membrane protein incorporation and crystallization from the lipidic cubic phase (LCP). In addition, Thomas performed scattering studies on nanolipoprotein particles (NLPs), also known as “Nanodiscs,” assembled using a novel cell-free expression method. Modeling of the scattering data demonstrated that NLPs assembled in this way were structurally equivalent to traditionally-assembled NLPs.

In 2018, Thomas joined the NIST Biomolecular Structure and Function Group as a staff physicist, with a joint appointment at the Institute of Bioscience and Biotechnology Research (IBBR). IBBR is a joint research institute composed of groups from NIST, the University of Maryland College Park (UMD), and the University of Maryland Baltimore (UMB). His current research involves developing methods for the joint application of scattering and cryogenic electron microscopy (CryoEM) to heterogeneous systems, where traditional single-particle CryoEM by particle averaging is inapplicable. These include systems with conformational heterogeneity (e.g., flexible proteins such as antibodies) or compositional heterogeneity (such as protein/membrane/surfactant assemblies that may include a distribution of stoichiometries). Specific systems include advanced vaccine and gene therapy formulations, e.g. LNPs and viral vectors, as well as biotherapeutics such as monoclonal antibodies. He also currently serves as co-manager of the NIST/IBBR CryoEM facility.

Publications

Characterization of AI Model Configurations For Model Reuse

Author(s)
Peter Bajcsy, Daniel Gao, Michael Paul Majurski, Thomas Cleveland, Manuel Carrasco, Michael Buschmann, Walid Keyrouz
With the widespread creation of artificial intelligence (AI) models in biosciences, bio-medical researchers are reusing trained AI models from other

Ionization and Structural Properties of mRNA Lipid Nanoparticles that Influence Expression in Intramuscular and Intravascular Administration

Author(s)
Manuel Carrasco, Suman Alishetty, Mohamad-Gabriel Alameh, Hooda Said, Lacey Wright, Mikell Paige, Ousamah Soliman, Drew Weissman, Thomas Cleveland, Alexander Grishaev, Michael Buschmann
Lipid Nanoparticles (LNPs) are used to deliver siRNA and COVID-19 mRNA vaccines. The main factor known to determine their delivery efficiency is the pKa of the

Design of a novel, native-like secreted form of the hepatitis C virus E1E2 heterodimer

Author(s)
Johnathan D. Guest, Ruixue Wang, Khadija Elkholy, Andrezza Chagas, Kinlin L. Chao, Thomas Cleveland, Young C. Kim, Zhen-Yong Keck, Alexander Marin, Roy Mariuzza, Alexander K. Andrianov, Eric A. Toth, Steven Foung, Brian Pierce, Thomas R. Fuerst
Hepatitis C virus (HCV) is a major worldwide health burden, and a preventive vaccine is needed for global control or eradication of this virus. A substantial

Structure of the cell-binding component of the Clostridium difficile binary toxin reveals a di- heptamer macromolecular assembly

Author(s)
Xingjian Xu, Raquel Ruiz, Kaylin Adipietro, Christopher Peralta, Danya Ben-Hail, Kristen Varney, Mary Cook, Braden Roth, Paul Wilder, Thomas Cleveland, Alexander Grishaev, Heather Neu, Sarah Michel, Wenbo Yu, Dorothy Beckett, Richard Rustandi, Alex MacKerell, Amedee des Georges, Edwin Pozharski, David Weber
Targeting Clostridium difficile infection is challenging because treatment options are limited, and high recurrence rates are common. One reason for this is
Created March 26, 2019, Updated September 14, 2023