Peptide and Protease Targets in Brain Disorders for Drug Discovery
Skaggs School of Pharmacy and Pharmaceutical Sciences
Department of Neuroscience and Department of Pharmacology, School of Medicine
The focus of research in the Hook Laboratory is to identify peptide and protease neurochemical mechanisms as new drug target strategies for brain disorders including neurological, neurodegenerative, and mental health diseases. The research addresses discovery of new drug strategies for Alzheimer’s and Huntington’s neurodegenerative diseases, traumatic brain injury (TBI), chronic pain, and mental health conditions of schizophrenia and bipolar disease. The neurochemical drug target strategies involve neurotransmitter profiling analyses by peptidomics and metabolomics mass spectrometry combined with proteomics, chemical biology of protease targets, genetics, via human brain focused investigations. Drug discovery combines evaluation of marine natural products with analyses of clinical drug molecules. This research addresses the unmet need for new therapeutic drugs to treat brain disorders
Education: B.S. in Biomedical Sciences, UC Berkeley; Ph.D. in Pharmacology, UC San Francisco.
Awards and Honors: Pharmacology Research Fellow (PRAT), Burroughs Wellcome Scientist Award (NIH Career Award, J & J Focused Giving Award, NIH grant review committee, Journal of Biological Chemistry Editorial Board (2014-2019), NARSAD Distinguished Investigator Award (2014-2015).
Leadership Experience: Chair of the SSPPS Faculty, Chair SPPSCAP Academic Review Committee, Chair Research Committee, Chair Faculty Recruitment Committee, Chair SSPPS Graduate Education, Director of NIH Training Program in Neurosciences, Director of the Graduate Training Program in Pharmaceutical Sciences and Drug Development.
- Pharmaceutical Biochemistry for Pharmacy students
- Molecular Neurobiology, Proteomics, Drug Mechanisms, and Research Proposal Design for Graduate students.
- Principles of Drug Discovery and Development for graduate students.
- Research Internships for graduate, pharmacy and undergraduate students.
- Protease Pathways for Peptide Neurotransmitter Production, Chemical Biology, Mass Spectrometry
- Alzheimer’s and Neurodegenerative Disease Protease Drug Targets. Alzheimer’s disease (AD), Huntington’s disease, and other neurodegenerative diseases produce neurotoxic peptides by proteases. These proteases represent new drug targets for discovery of novel therapeutic agents.
- Traumatic Brain Injury (TBI) protease drug target prevents cell death and brain dysfunction.
- Chronic pain is improved by targeting spinal dynorphin neurotransmitter.
- Neurotransmitter Profiling by Mass Spectrometry in Brain Disorders: Drug Targets and Biomarkers.
- Modeling of Schizophrenia and Brain Neurons by Human Induced Pluripotent Stem Cell Neurons.
- Hook et al (2018). Diversity of neuropeptide cell-cell signaling molecules generated by proteolytic processing revealed by neuropeptidomics mass spectrometry. J Am Soc Mass Spectrom. 29(5), 807-816.
- Bouttee et al (2020). Penetrating traumatic brain injury triggers dysregulation of cathepsin B protein levels independent of cysteine protease activity in brain and cerebral spinal fluid. J Neurotrauma 37(13):1574-1586.
- Podvin et al (2020). Dysregulation of exosome cargo by mutant tau expressed in human-induced pluripotent stem cell (iPSC) neurons revealed by proteomics analyses. Mol Cell Proteomics 9, 1017-1034.
- Hook et al (2020). Cathepsin B in neurodegeneration of Alzheimer's disease, traumatic brain injury, and related brain disorders. Biochim Biophys Acta Proteins Proteom. 1868, 140428.
- Yoon et al (2021) Selective neutral pH inhibitor of cathepsin B designed based on clvage preferences at cytosolic and lysosomal pH conditions. ACS Chem Biol. 16, 1628-1643.
- Alzheimer’s, Huntington's and neurodegenerative diseases
- Traumatic Brain Injury (TBI)
- Chronic pain
- Biomarkers via neurotransmitter MS/MS profiling