Location

Jacksonville, Florida

Contact

Caulfield.Thomas@mayo.edu

SUMMARY

As a computational chemist-scientist with a multidisciplinary training in biochemistry, biophysics, computer-aided modeling and in silico drug modeling, Thomas Caulfield, Ph.D., is interested in studying molecular targets with clinical potential for future "drugability."

Dr. Caulfield's laboratory is focused on investigating structure-function behavior of neurological disease targets and cancer biology targets from a dynamics behavior viewpoint for proteins, protein-protein interactions or nucleic acid complexes. The complex interplay between molecular targets, which is central to cellular pathways, can be examined at the level of the gene, message transcript, protein and various macroscopic readouts. Dr. Caulfield's laboratory is primarily interested in the atomic level of detail that governs the interactions of the cellular components.

As a scientist, Dr. Caulfield's expertise is in molecular simulations, virtual screening of large libraries of compounds for targets, in silico modeling of proteins and nucleic acids, de novo drug design for inhibitors and activators, and complex structural data analyses for molecular partners. Dr. Caulfield's collaborative research includes work with several laboratories, including those of Asher A. Chanan-Khan, M.D.; John A. Copland III, Ph.D.; Leonard Petrucelli, Ph.D.; Evette S. Radisky, Ph.D.; Wolfdieter Springer, Ph.D.; and Han W. Tun, M.D. The principal aim of these collaborations is to accelerate drug discovery and focus experimental design for improved efficiency.

Currently, Dr. Caulfield has ongoing collaborations with colleagues at University of California, Riverside; Ichan School of Medicine at Mount Sinai; and Uppsala University, Sweden.

Focus areas

  • Neurodegeneration. Dr. Caulfield receives National Institutes of Health RO1 funding for Parkinson's disease research. Specifically, he studies Parkin protein dynamics and model structure-function behavior of Parkin mutants' effect on mitophagy. In collaboration with Dr. Springer, Dr. Caulfield is screening and designing "activators" that will enhance Parkin translocation to the mitochondria, with funding from The Michael J. Fox Foundation.
  • Dual inhibitors to slow tumorogenesis. Dr. Caulfield is focused on resistant strains of blood cancer. His research team is focused on delivering dual inhibitors that may be employed in conjunction with the standard of care, to prevent onset of aggressive resistant relapse.
  • Renal cell cancer collaboration. Dr. Caulfield is investigating the effect of the enzyme SCD1 on the endoplasmic reticulum (ER) stress-signaling pathway as well as the correlation between inhibition of SCD1 and inhibition of tumor development in associated cancers. In collaboration with Dr. Copland's Cancer Biology and Translational Oncogenomics Laboratory, new SCD1 inhibitors with novel (and patentable) compound structures have been developed (in silico) and then synthesized and tested for activity.
  • Brain lymphoma. Other cancer projects include investigation of CNS specific compounds, such as Agelastatin A analogs, neurological tumors and osteopontin-related cancers in collaboration with Dr. Tun.
  • Drug and technology development. Dr. Caulfield also serves as a principle investigator for studies on ribosome modeling and design of next-generation antibiotics; antimalarial compounds; anti-aging compounds modeled in "wheelhouse" organisms (rotifera); and computational methods development for improving cutting-edge technologies including docking, simulations and complex data analyses.

Significance to patient care

Dr. Caulfield anticipates that through his accelerated drug discovery and research platform, small molecule modulators for selected targets can be devised to help study the cellular pathways related to these targets. This in turn allows a better understanding of the important protein targets. The ultimate goal of his research is to develop novel pharmacological interventions that can prevent and treat diseases with clearly identified macromolecular targets.

Professional highlights

  • Co-investigator, Molecular Mechanisms of Parkin-Directed Mitochondrial Quality Control, research project grant, National Institutes of Health, 2014-2019
  • Co-investigator, Identification of Parkin Activators Through Structure-Function Analyses, The Michael J. Fox Foundation Award, 2014-2015
  • Journal reviewer, Nature Structural & Molecular Biology (2014-present); PLOS Computational Biology (2014-present); Molecular BioSystems, Royal Society of Chemistry (RSC) (2013-present); Computational and Structural Biotechnology Journal (2013-present); MedChemComm, RSC (2012-present); BioMed Central online publisher (2012-present)

PUBLICATIONS

See my publications

PROFESSIONAL DETAILS

Administrative Appointment

  1. Associate Consultant I-Research, MCF Neuroscience

Academic Rank

  1. Assistant Professor of Neuroscience

EDUCATION

  1. Research Fellowship - Drug discovery in neuroscience & cancer Mayo Clinic
  2. Post-Doc - Drug discovery, cancer, neuro, diabetes, apoA, apoE Torrey Pines Institute for Molecular
  3. Visiting Scholar - Chromatin Remodeling, Biophysics, Nanoengineering University of California, San Diego
  4. Ph.D. - Chemistry, Minor: Biophysics/Biochemistry Georgia Institute of Technology
  5. MS - Chemistry, Minor: Biochemistry Georgia Institute of Technology
  6. BS - Physics University of Florida
.
BIO-00055161

Mayo Clinic Footer