Our research

Our projects include:

Macrofilaricide studies to find lead compounds that treat filarial diseases in life cycle stages where current treatment is ineffective. Lead compounds that have approved as safe and can be repurposed to treat neglected diseases are of particular interest. This includes screening of drug libraries to find safe lead compounds that may have previously unknown efficacy in treating diseases. Currently, our research includes searches for macrofilaricides for the organisms causing river blindness (Onchocerca volvulus) and lymphatic filariasis (Wuchereria bancrofti, Brugia malayi, and Brugia timori) using a model based of a Brugia pahangi model. 

An example can be seen in our publication:
Bulman CA, Bidlow CM, Lustigman S, Cho-Ngwa F, Williams D, Rascón AA, Tricoche N, Samje M, Bell A, Suzuki B, Lim KC, Supakorndej N, Supakorndej P, Wolfe AR, Knudsen GM, Chen S, Wilson C, Ang KH, Arkin M, Gut J, Franklin C, Marcellino C, McKerrow JH, Debnath A, Sakanari JA. Repurposing auranofin as a lead candidate for treatment of lymphatic filariasis and onchocerciasis. PLoS Negl Trop Dis. 2015 Feb; 9(2):e0003534. PMID: 25700363.

Separating Males from females

In Vitro screening of leads and high throughput analysis of compounds is a major focus of the laboratory. Our team recently developed a low cost, simple visual imaging system that utilizes a novel software program to capture video recordings to assay compounds against these large worms. Instead of depending on laborious manual subjective methods of analyzing the data, we can now quantify multiple worms' movements simultaneously on a single plate, with each plate taking only a few seconds to read. We also research other areas of parasitic disease, including characterizing various parasite proteins as potential drug targets.

The technique is discussed in our publication:
Storey B, Marcellino C, Miller M, Maclean M, Mostafa E, Howell S, Sakanari J, Wolstenholme A, Kaplan R. Utilization of computer processed high definition video imaging for measuring motility of microscopic nematode stages on a quantitative scale: "The Worminator". Int J Parasitol Drugs Drug Resist. 2014 Dec; 4(3):233-43. PMID: 25516834.
and
Marcellino C, Gut J, Lim KC, Singh R, McKerrow J, Sakanari J. WormAssay: a novel computer application for whole-plate motion-based screening of macroscopic parasites. PLoS Negl Trop Dis. 2012 Jan; 6(1):e1494. PMID: 22303493; PMCID: PMC3269415

Plate 2

Noninvasive diagnostics to measure the viability of Onchocerca nodules are being tested to find fast and convenient methods to determine the effectiveness of drug treatments directly inside a patient without surgical intervention. 

nodules

Continuing studies in drug models for Cryptosporidium to explore the biochemistry and biology of the protozoa to find effective treatments for a disease that is the most common water-borne illness in the world. 

Crypto

Schistosoma mansoni studies in pursuit of diagnostic and therapeutic solutions for a helminth disease that is second only to malaria as the most common parasitic disease. We maintain a cell line for use in drug discovery and screening studies. 

A publication of interest is:
Ingram JR, Rafi SB, Eroy-Reveles AA, Ray M, Lambeth L, Hsieh I, Ruelas D, Lim KC, Sakanari J, Craik CS, Jacobson MP, McKerrow JH. Investigation of the proteolytic functions of an expanded cercarial elastase gene family in Schistosoma mansoni. PLoS Negl Trop Dis. 2012; 6(4):e1589. PMID: 22509414; PMCID: PMC3317910.

Schisto

Planaria studies include the flatworm, Schmidtea mediterranea, as a safe and convenient model for parasitic study due to its conservation of key proteases and ease of manipulation. 

Planeria