Professor, Department of Biology
Ph.D. University of California, San Diego
B.S. Massachusetts Institute of Technology
Upcoming Seminar: 4/7/2016
Office: 209 Huestis
Research Interests: Technology development for drug screening platforms, including anthelmintic (anti-nematode worm) drugs for human and animal health; nematode neurobiology and genetics; synaptic physiology; neural circuits for behavior; insect neurobiology; tropical infectious and parasitic diseases; research and education capacity building in Africa.
Overview: Traditionally, research in the Weeks lab investigated hormonal regulation of the structure, function and survival of neurons and neural circuits, using methods including electrophysiology, biophysics, genetics, genomics and behavioral analysis. This work focused on an extreme example of natural neural plasticity: insect metamorphosis in the moth, Manduca sexta, and fruit fly, Drosophila melanogaster, when neural circuits are reorganized to accommodate different life stages. Hormones similarly influence the vertebrate nervous system with relevance to human health such as Alzheimer's Disease and stress-induced cognitive decline.
Since the mid-1990s, Weeks has increasingly been involved with research and education in Africa, and the study of tropical parasitic and infectious diseases. Infection with parasitic nematodes causes chronic, debilitating disease in humans and animals in many resource-limited regions of the world. Existing anthelmintic (anti-nematode) drugs are losing potency due to increasing drug resistance in the parasites, and new drugs are critically needed. Within this context, the Weeks lab turned its focus to the small roundworm, Caenorhabditis elegans, a powerful model organism for biological inquiry. The Weeks lab is using combined microfluidic and electrophysiological platforms developed with Shawn Lockery to accelerate the screening process for new anthelmintic drugs, using C. elegans. The ScreenChip platform is also useful for C. elegans models of human aging and disease. Recently, the Bill & Melinda Gates Foundation funded the successful modification of this technology for use with human parasites such as hookworm (Ancylostoma spp.) and roundworm (Ascaris). In 2011, Weeks and Lockery founded a UO spin-off company, NemaMetrix Inc., to enhance commercialization of these devices.
Weeks has taught in and organized advanced neuroscience courses throughout Africa (e.g., Senegal, Egypt, Kenya, Democratic Republic of Congo, South Africa, Ghana) for graduate and medical students, and neuroscience faculty, under the auspices of the International Brain Research Organization. A member of the African Studies Program, Weeks performs healthcare fieldwork in Zimbabwe and is a student and performer of Zimbabwean music. At UO, she teaches courses in global health [“Tropical Diseases in Africa” (Bi309) and “HIV/AIDS in Africa” (CHC434)] and helps direct a global-health-focused study abroad and internship program in Accra, Ghana, for undergraduates.
Microfluidic platform for electrophysiological recordings from host-stage hookworm and Ascaris suum larvae: a new tool for anthelmintic research. Weeks JC, Roberts WM, Robinson KJ, Keaney M, Vermeire JJ, Urban Jr., JF, Lockery SR, Hawdon JM.. International Journal for Parasitology: Drugs and Drug Resistance, in press.
Anthelmintic drug actions in resistant and susceptible C. elegans revealed by electrophysiological recordings in a multichannel microfluidic device.
Int J Parasitol Drugs Drug Resist. 2018 Dec;8(3):607-628
Authors: Weeks JC, Robinson KJ, Lockery SR, Roberts WM
Many anthelmintic drugs used to treat parasitic nematode infections target proteins that regulate electrical activity of neurons and muscles: ion channels (ICs) and neurotransmitter receptors (NTRs). Perturbation of IC/NTR function disrupts worm behavior and can lead to paralysis, starvation, immune attack and expulsion. Limitations of current anthelmintics include a limited spectrum of activity across species and the threat of drug resistance, highlighting the need for new drugs for human and veterinary medicine. Although ICs/NTRs are valuable anthelmintic targets, electrophysiological recordings are not commonly included in drug development pipelines. We designed a medium-throughput platform for recording electropharyngeograms (EPGs)-the electrical signals emitted by muscles and neurons of the pharynx during pharyngeal pumping (feeding)-in Caenorhabditis elegans and parasitic nematodes. The current study in C. elegans expands previous work in several ways. Detecting anthelmintic bioactivity in drugs, compounds or natural products requires robust, sustained pharyngeal pumping under baseline conditions. We generated concentration-response curves for stimulating pumping by perfusing 8-channel microfluidic devices (chips) with the neuromodulator serotonin, or with E. coli bacteria (C. elegans' food in the laboratory). Worm orientation in the chip (head-first vs. tail-first) affected the response to E. coli but not to serotonin. Using a panel of anthelmintics-ivermectin, levamisole and piperazine-targeting different ICs/NTRs, we determined the effects of concentration and treatment duration on EPG activity, and successfully distinguished control (N2) and drug-resistant worms (avr-14; avr-15; glc-1, unc-38 and unc-49). EPG recordings detected anthelmintic activity of drugs that target ICs/NTRs located in the pharynx as well as at extra-pharyngeal sites. A bus-8 mutant with enhanced permeability was more sensitive than controls to drug treatment. These results provide a useful framework for investigators who would like to more easily incorporate electrophysiology as a routine component of their anthelmintic research workflow.
PMID: 30503202 [PubMed - in process]
Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing.
Sci Rep. 2018 01 17;8(1):975
Authors: Weeks JC, Roberts WM, Leasure C, Suzuki BM, Robinson KJ, Currey H, Wangchuk P, Eichenberger RM, Saxton AD, Bird TD, Kraemer BC, Loukas A, Hawdon JM, Caffrey CR, Liachko NF
Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. To expedite drug discovery, we screened a small-molecule library of compounds with histories of use in human clinical trials for anthelmintic activity against the soil nematode Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life stages including embryos, developing larvae and gravid adults. These drugs act rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline, paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris whipworms, prevent hatching and development of Ancylostoma caninum hookworms and kill Schistosoma mansoni flatworms, three widely divergent parasitic helminth species. C. elegans mutants with resistance to known anthelmintic drugs such as ivermectin are equally or more susceptible to these three drugs, suggesting that they may act on novel targets to kill worms. Sertraline, paroxetine, and chlorpromazine have long histories of use clinically as antidepressant or antipsychotic medicines. They may represent new classes of anthelmintic drug that could be used in combination with existing front-line drugs to boost effectiveness of anti-parasite treatment as well as offset the development of parasite drug resistance.
PMID: 29343694 [PubMed - indexed for MEDLINE]