Zvi Kelman

Research Biologist

Kelman Group

Contact

Email: zkelman@umd.edu

Call: (240) 314-6294

Education

  • Helen Hay Whitney Foundation Post-Doctoral Fellow, Memorial Sloan-Kettering Cancer Center, 1997-2000
  • Helen Hay Whitney Foundation Post-Doctoral Fellow, Johns Hopkins School of Medicine, 1995-1996
  • Ph.D., Molecular Biology, Cornell University Graduate School of Medical Sciences, New York, 1995
  • MSc., Cell Biology, Weizmann Institute of Science, Rehovot, Israel, 1989
  • BSc., Agriculture, Hebrew University of Jerusalem, Rehovot, Israel, 1987

Profile

Dr. Zvi Kelman’s research is focused on developing tools and reagents for the labeling of biomolecules with stable isotopes to support biophysical and bioanalytical measurements. The NIST Biomolecular Labeling Laboratory also provides support to external users through a proposal process. The Kelman laboratory has the equipment and reagents necessary for production, purification, and characterization of labeled proteins and other biomolecules, including peptides and nucleic acids. 

The lab also studies the mechanism of DNA replication in archaea and other organisms. Through biochemical, structural, and genetic approaches, the lab studies the initiation and elongation phases of DNA replication using the thermophilic archaeon Thermococcus kodakarensis as a model organism.

(Left) Ishino, S., Kelman, L., Kelman, Z. and Ishino, Y. (2013). The archaeal DNA replication machinery: past, present and future. Genes Genet. Syst. 88, 315-319.
(Right) Altieri, A.S., Ladner, J.E., Li, Z., Robinson, H., Sallman, Z.F., Marino, J.P. and Kelman, Z. (2016). A small protein inhibits proliferating cell nuclear antigen by breaking the DNA clamp. Nucleic Acids Res. 44, 6232-6241.

CURRENT RESEARCH

Expression and purification of monoclonal antibodies

Monoclonal antibodies (mAbs) are commonly developed by the pharmaceutical industry as drugs to fight a large variety of diseases, including cancer and autoimmune disease. Some structural studies on mAbs will benefit from the ability to label the antibodies with stable isotopes, including 2H, 13C, and 15N. The lab is developing tools for Escherichia coli expression and purification of full-length labeled mAbs, as well as Fc and Fab antibody fragments.

Labeled protein expression in yeast

Overexpression of recombinant proteins in yeast enables studies of eukaryotic proteins that require post-translational modifications by pathways that are not present in E. coli. However, in yeast, overexpression of recombinant proteins is reduced several-fold in 2H-enriched media. The lab is using the yeast Pichia pastoris as a model organism to improve protein production in the presence of 2H2O. Using a combination of mutagenesis and genetic manipulation, the team is engineering P. pastoris cells that can produce high levels of labeled protein in high (>85%) 2H2O growth conditions.

Studies on the archaeal primase

During the study of T. kodakarensis primase, the Kelman lab discovered a unique enzymatic activity. In the presence of dATP and small molecules (SM) with an OH group, the enzyme will make an AMP-SM adduct. The lab is using structure-based mutagenesis to modify the enzyme and enable it to form adducts between larger molecules and additional nucleotides, including deoxy- and ribonucleotides.

Publications
2021
Preface.
Preface.
The emerging landscape of single-molecule protein sequencing technologies.
Recombinant expression of computationally designed peptide-bundlemers in Escherichia coli.
Creation and filtering of a recurrent spectral library of CHO cell metabolites and media components.
2020
Leveraging nature's biomolecular designs in next-generation protein sequencing reagent development.
Unwinding 20 Years of the Archaeal Minichromosome Maintenance Helicase.
2019
Strategies for Development of a Next-Generation Protein Sequencing Platform.
Characterization of the internal translation initiation region in monoclonal antibodies expressed in Escherichia coli.
Editorial: The DNA Replication Machinery as Therapeutic Targets.
Engineering ClpS for selective and enhanced N-terminal amino acid binding.
Neutron scattering in the biological sciences: progress and prospects.
2018
DNA Sliding Clamps as Therapeutic Targets.
Platform development for expression and purification of stable isotope labeled monoclonal antibodies in Escherichia coli.
Heterologous recombinant expression of non-originator NISTmAb.
Archaeal DNA replication and repair: new genetic, biophysical and molecular tools for discovering and characterizing enzymes, pathways and mechanisms.
2017
Do Archaea Need an Origin of Replication?
Genome Replication in Thermococcus kodakarensis Independent of Cdc6 and an Origin of Replication.
The GAN Exonuclease or the Flap Endonuclease Fen1 and RNase HII Are Necessary for Viability of Thermococcus kodakarensis.
2016
A small protein inhibits proliferating cell nuclear antigen by breaking the DNA clamp.