V. Jo Davisson
Title:
Professor of Medicinal Chemistry and Molecular Pharmacology
PhD Granting Institution:
University of Utah
Contact:
Email Address: davisson@purdue.edu
Office Phone: 765-494-5238
Lab Website Link: https://www.mcmp.purdue.edu/faculty/davisson
Primary Training Group:
Chemical Biology
Secondary Training Groups:
Biomolecular Structure and Biophysics, Computational and Systems Biology
Research Areas:
Our active core research programs can be stated in 3 broad areas. 1) To discover and develop selective antagonists/agonists of protein assemblies relevant to therapeutic cancer interventions. The current target systems under investigation involve various cellular roles, including: DNA replication and repair cellular vesicle transport and pH control viral-mediated oncogenesis While the first 30 years of research focused primarily on metabolic enzymatic targets, all of the molecular systems under the current investigation are considered non-classical or “undruggable” targets. Our efforts aim to discover and develop small molecule probes of these target systems to address their specific roles in disease contexts and serve as leads for drug discovery. A significant effort is devoted to exploring new approaches to designing and discovering useful chemotypes and drug leads for each target system. We develop probes to test hypotheses regarding protein network interactions and define new target binding sites. Currently, biomolecular screening methods are integrating with computational approaches and novel synthetic chemical libraries to enhance the success of the discovery process. 2) To harness chemical scaffolds and mechanisms of action of natural product drugs. A long-standing interest is in understanding molecular mechanisms of drug actions. Part of the inspiration comes from the rich biological activities of natural products and their synthetic analogs, which have the potential to be developed into new drug therapies. Natural products as molecular tools continue to provide rich sources for drug target discovery and/or serve as starting point scaffolds for designing new therapeutics. We continue to pursue biochemical/proteomic and biophysical/structural biology approaches to understand and exploit the cellular pharmacology of natural products in future drug design. The current projects focus on: Natural product scaffolds that modulate the function of vacuolar-ATPase (v-ATPase) for drug development as antivirals and anti-metastatic activities. The use of ligand-based and structure-based drug design approaches to discover new and improved selective modulators of V-ATPase isoforms 3) To develop or utilize novel high-content, quantitative, phenotypic-based screens for molecular discovery and evaluation. These collaborative efforts involve platform development bridging with chemical biology using bioengineering and data sciences approaches. The variation of biological response to chemical effects as a function of genetic content in biological systems is a problem for integrating genomics and proteomics with high-content phenotypic assay systems. Our collaborative efforts aim to use innovative biosystem screens to evaluate new agents' efficacy, toxicity, or pharmacokinetic properties. Insights from these efforts offer an understanding of how best to target susceptibilities and stage drug therapies from discovery through development. The current projects involve: The use of zebrafish models to guide the development of novel toxicant countermeasures with a current focus on treatments for cyanide exposure; Molecular interventions for mitochondrial dysfunctions to counteract neurodegenerative diseases.
Current Projects:
Area 1: The specific project targets currently under investigation include: >cell proliferating nuclear antigen (PCNA) >human papillomavirus virus E6 protein (HPV-E6) >nuclear localized EGFR and DNA-PK Area 2: The current projects focus on: >Natural product scaffolds that modulate the function of vacuolar-ATPase (v-ATPase) for drug development as antivirals and anti-metastatic activities. >The use of ligand-based and structure-based drug design approaches to discover new and improved selective modulators of V-ATPase isoforms Area 3: The current projects involve: >The use of zebrafish models to guide the development of novel toxicant countermeasures with a current focus on treatments for cyanide exposure >Molecular interventions for mitochondrial dysfunctions to counteract neurodegenerative diseases.
Importance of Interdisciplinary Research:
The general interests are at the intersection of chemistry and disease biology to enhance the drug discovery and development process. Our character is to engage in collaborative efforts to enhance the overall approaches to addressing these objectives and promote the translation to the clinic.