Philadelphia University + Thomas Jefferson University

Pascal, John

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jmp007

John M. Pascal, PhD

Contact Dr. Pascal

233 South 10th Street
Suite 804
Philadelphia, PA 19107

(215) 503-4596
(215) 923-2117 fax

Research and Clinical Interests

Structural biology of DNA replication, repair and signaling mechanisms; mechanisms of genome maintenance and chromosomal metabolism; biochemical and biophysical studies of nucleic ACID enzymes; macromolecular x-ray crystallography
We study protein structure and function to understand how cells replicate and repair DNA, and how the integrity of the genome is preserved during these processes. A major objective is to determine the three-dimensional structure of proteins to visualize how their architecture and design are related to their functions in the cell. We are particularly interested in the proteins that detect and respond to breaks in the structure of DNA, a common and potentially lethal form of DNA damage. X-ray crystallography is our primary tool for determining the structures of proteins and protein-DNA complexes. We also use other biophysical techniques, biochemical tools, and cell biological approaches to assay protein structure and function.

Publications

Most Recent Peer-Reviewed Publications

  1. NAD+analog reveals PARP-1 substrate-blocking mechanism and allosteric communication from catalytic center to DNA-binding domains
  2. Posttranscriptional regulation of PARG mRNA by HuR facilitates DNA repair and resistance to PARP inhibitors
  3. Purification of DNA damage-dependent PARPs from E. coli for structural and biochemical analysis
  4. The nucleosomal surface is the main target of histone ADP-ribosylation in response to DNA damage
  5. Fluorescent sensors of PARP-1 structural dynamics and allosteric regulation in response to DNA damage
  6. Tail and Kinase Modules Differently Regulate Core Mediator Recruitment and Function In Vivo
  7. Tankyrase-1 Ankyrin Repeats Form an Adaptable Binding Platform for Targets of ADP-Ribose Modification
  8. Evaluating Parp1 domains as gossypol targets
  9. Tankyrase Sterile α Motif Domain Polymerization Is Required for Its Role in Wnt Signaling
  10. A PARP1-ERK2 synergism is required for the induction of LTP
  11. Structural Basis of Detection and Signaling of DNA Single-Strand Breaks by Human PARP-1
  12. PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain
  13. PARP-2 domain requirements for DNA damage-dependent activation and localization to sites of DNA damage
  14. Akt kinase C-terminal modifications control activation loop dephosphorylation and enhance insulin response
  15. The rise and fall of poly(ADP-ribose): An enzymatic perspective
  16. Quantitative site-specific ADP-ribosylation profiling of DNA-dependent PARPs
  17. Discovery and structure-activity relationship of novel 2,3- dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2 h)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 Inhibitors
  18. PARP-2 and PARP-3 are selectively activated by 5' phosphorylated DNA breaks through an allosteric regulatory mechanism shared with PARP-1
  19. Selective phosphorylation modulates the PIP 2 sensitivity of the CaM-SK channel complex
  20. Targeting PARP-1 allosteric regulation offers therapeutic potential against cancer