Staff Profile: Mark J. Henderson

Mark J. Henderson, Ph.D.

Biology Group Leader

Division of Pre-Clinical Innovation
Early Translation Branch (Contractor)

National Center for Advancing Translational Sciences

National Institutes of Health

Email Mark J. Henderson

Biography

Mark Henderson is a biology group leader in the Early Translation Branch (Thymine Team). Henderson collaborates with both academic and NIH investigators on projects that span a wide range of biological targets. These projects aim to identify small molecules that can be used to understand and/or modulate pathogenic events. He has experience in the design, development and implementation of biochemical and cell-based screening assays using diverse technologies.

Henderson received his doctorate in cellular and molecular medicine from the Johns Hopkins School of Medicine and his bachelor’s degree in biological sciences from North Carolina State University. He then trained as a research fellow under Brandon K. Harvey, Ph.D., at the National Institute on Drug Abuse, where he developed cell-based reporters to study endoplasmic reticulum calcium homeostasis. He has authored more than 30 peer-reviewed scientific publications.

Research Topics

Henderson’s research is focused on studying cellular processes that are dysregulated across multiple disorders (e.g., endoplasmic reticulum dysfunction and protein folding/trafficking). He and his team are devising high-throughput screening assays to identify small molecules that can modulate disease-relevant phenotypes in the following areas:

  • Neurodegeneration (e.g., Huntington’s disease, Parkinson’s disease)
  • Cancer (e.g., metastatic processes)
  • Rare disorders (e.g., Wolfram syndrome)
  • Protein misfolding (e.g., cystic fibrosis, lysosomal storage disorders)
  • Immunology (e.g., macrophage activation, inflammation)

Henderson also has interests in developing novel reporters and screening technologies. For example, he and his colleagues developed a high-throughput cellular thermal shift assay (CETSA) that can be used to detect small-molecule binding to a protein target in the cellular environment.

Selected Publications

  1. A widely-applicable high-throughput cellular thermal shift assay (CETSA) using split Nano Luciferase.
  2. SERCaMP: a carboxy-terminal protein modification that enables monitoring of ER calcium homeostasis.
  3. A Low Affinity GCaMP3 Variant (GCaMPer) for Imaging the Endoplasmic Reticulum Calcium Store.
  4. High-throughput screening with nucleosome substrate identifies small-molecule inhibitors of the human histone lysine methyltransferase NSD2.
  5. Nuclear export of misfolded SOD1 mediated by a normally buried NES-like sequence reduces proteotoxicity in the nucleus.