1. Research
1. Development of insecticides targeting G protein-coupled receptors
I have been interested in developing insecticidal compounds targeting pest neuropeptidergic systems. I have selected two different target systems for different ranges of the spectra as pesticides: one targeting the ecdysis triggering hormone (ETH) system, having a broad spectrum, but still remaining limited to arthropods, and the other is the proctolin system that is lacking in bees, but selectively targets the parasitic acari. We used high throughput screening of the 75,000 compound chemical library using the ETH receptor expressed in a cell line. We currently focus on 12 lead compounds after negative screening and confirmation assays.
I developed an idea based on comparative genetics to develop taxon-specific peptidomimetics. A mite-specific peptidergic proctolin system, lacking in honey bee, was targeted to develop a bee-safe acaricide, proctolin mimetic chemical. So far we found the peptidomimetics are safe to honeybees, while it was orally toxic to Varroa mites. I believe the achievements that we have made require a few more final steps to be applicable in the field. I am further investigating a number of similar cases utilizing comparative genomics-based selective pesticide development. These studies have been in the nexus of comparative genomics, pharmacological tool development, and insecticide toxicology by forming a collaborative group among scientists, Drs. Troy Anderson (U of Nebraska), Ron Nachman (USDA-ARS, Texas), and Ho Ng (K-State). This group of projects has been supported by NIH-R21 and USDA-NIFA and is being further developed for proposals for the next round of funding.
2. Disruption of tick osmoregulatory pathways
Ticks are obligatory ectoparasites that feed on the blood of vertebrate hosts and often transmit pathogens, including bacteria, protozoa, and viruses. The osmoregulation of tick is an important physiology for survival in both off-host tick and feeding stage ticks. The tick physiology relevant to water conservation mechanisms includes directly drinking water, dermal excretions, and deficaiton. We investigate these processes at the behavior, physiology, and molecular levels. In the course of investigations, we found several neuropeptides and biogenic amines are involved in osmoregulation. The physiological and molecular mechanisms involving the signaling molecules are being further investigated. Ultimately, we will develop the means to disrupt the tick osmoregulation in control of this medically important pest.
3. Tick bites as the sensitizer of alpha-gal syndrome (or red meat allergy)
Tick bites (Amblyomma americanum in US) are thought to be the cause of AGS in humans, diagnosed by 3 – 5 hour delayed urticaria and anaphylaxis to dietary red meat. It is caused by an unusual occurrence of enhanced IgE antibody production against galactose-alpha-1,3-galactose (aGal), which is a common glycan in mammalian tissue with the exceptions of old word monkeys and humans. We recently have tested “transmission hypothesis” of the aGal (supported by DoD) by using a mutant murine model system alpha-galatosyltransferase knock out strain, in which the hypothesis was NOT supported. In the course of the extended study, we found that the ticks fed on human blood show significantly higher levels of aGal than the ticks fed on other mammalian blood with large individual tick variations.
