Peptide and Protease Targets in Brain Disorders for Drug Discovery
Skaggs School of Pharmacy and Pharmaceutical Sciences
Department of Neuroscience and Department of Pharmacology
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, Biotechnology.
- Pharmaceutical Biochemistry for Pharmacy students
- Molecular Neurobiology, Proteomics, Drug Mechanisms, and Research Proposal Design for Graduate students.
- Summer Research Internships for 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 (2008) Proteases for processing proneuropeptides into peptide neurotransmitters. Ann. Rev. Pharmacol. Tox. 48, 393-423.
Gupta et al (2010) Mass spectrometry based neuropeptidomics of secretory vesicles from human pheochromocytoma reveals novel peptide products. Journal of Proteome Res. 9, 5065-5075.
Hook, G. et al. (2011) The cysteine protease inhibitor, E64d, reduces brain amyloid-beta and improves memory deficit in Alzheimer’s disease animal models. J. Alzheimer’s Disease 26, 387-408.
Kindy, M. et al. (2012) Deletion of the cathepsin B gene improves memory deficits in a transgenic Alzheimer’s disease mouse model. Journal of Alzheimer’s Disease 29, 827-840.
Hook, G.R. et al. (2014) The cysteine protease cathepsin B is a drug target and cysteine protease inhibitors ae potential therapeutics for traumatic brain injury. Journal of Neurotrauma 31, 515-529.
Hook, V. et al. (2014) hiPSC neurons display activity-dependent neurotransmitter secretion: aberrant catecholamines in schizophrenia neurons. Stem Cell Reports 3, 531-538.
(from over 150)
- Alzheimer’s disease
- Huntington’s disease
- Schizophrenia, mental health
- Traumatic Brain Injury (TBI)
- Chronic pain
- Biomarkers via neurotransmitter MS/MS profiling