Development of Drugs and Diagnostics for Parasitic Diseases of Poverty
Associate Professor
Skaggs School of Pharmacy and Pharmaceutical Sciences
Drugs and Diagnostics for parasitic diseases of poverty
Infectious diseases associated with poverty, including the neglected tropical diseases, which are caused by eukaryotic pathogens (or parasites), are overlooked in terms of the number, quality and efficacy of the drugs available for treatment. As part of the Center for Discovery and Innovation in Parasitic Diseases (CDIPD) with a focus on schistosomiasis, hookworm disease and African trypanosomiasis. Three broad themes underpin my team’s research: (1) the identification and validation of protein targets (e.g., proteases and kinases) for drug development; (2) the pre-clinical and translational development of drugs, including the development and application of associated technologies (high-content and high-throughput screening platforms, RNA interference, C. elegans as a drug discovery model, protein expression and animal models of infection); and (3) development of point-of care (POC) diagnostics. To facilitate our cross-disciplinary research interests we interface with bioinformaticians, medicinal chemists, pharmaceutical chemists, structural biologists and automated systems biologists, and collaborate with academia and industry worldwide. Our team is also actively engaged in education and capacity-building by training or collaborating with researchers from low-/middle-income countries to translate tools and technologies back to their home institutions.
Education:
B.Sc. (Hons.) in Zoology, University College Dublin, Ireland (1988); Ph.D. in Molecular and Biochemical Parasitology, University College Dublin, Ireland (1994).
Awards and Honors:
Wellcome Trust Traveling Research Fellowship to Europe (1994-1996); Scientific American Magazine’s ‘SciAM50’ award for outstanding contributions to biomedical research (2007); Associate Editor for the Journal of Parasitology (2005-present); Specialist Editorial Board for the International Journal for Parasitology - Drugs and Drug Resistance (2011-present). Associate Editor to the journal Pharmaceuticals (2017-present).
Leadership Experience:
Director of the Biochemistry Core, Sandler Center for Drug Discovery, UCSF (2001-2011); Senior Scientist, Center for Discovery and Innovation in Parasitic Diseases, UCSF (2012-2014); Nematode and Trematode Core Director to the CDIPD at UCSD (2015-present); Vice-Chair UCSD-IACUC (2017-present).
- How parasite proteases contribute to parasitism
- Validated various proteins (e.g., proteases, kinases and phosphodiesterases) as drug targets for parasitic infections
- Identified assorted synthetic and natural product small molecule chemistries as leads for treatment of parasitic infections
- Co-developed a number of technologies for high throughput and high content screening, and automated image analysis of complex large parasites
- Long T et al. (2017). Phenotypic, chemical and functional characterization of cyclic nucleotide phosphodiesterase 4 (PDE4) as a potential anthelmintic drug target. PLoS Negl Trop Dis. 11(7):e0005680.
- Monti L et al. (2018). Brain-Penetrant Triazolopyrimidine and Phenylpyrimidine Microtubule Stabilizers as Potential Leads to Treat Human African Trypanosomiasis. ChemMedChem. 13(17):1751-1754
- Weeks et al. (2018). Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing. Sci Rep. 8(1):975.
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Collaborations with industry are a key component of our research. For example, we work with Merck, Calibr, J&J and Celgene to discover small molecule therapies of infectious diseases of poverty.
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We welcome industry training or placement opportunities for students interested in the drug discovery process. We recently hosted a J&J-supported pharmacy research fellow.