Research Associate, UCSD
Skaggs School of Pharmacy and Pharmaceutical Sciences
I have worked on research projects focused on a variety of diseases, including viral diseases, heart disease, anthrax, and cancer since 1996. I joined the CDIPD in 2014 and am using my background in developing laboratory disease models to study pathogenesis and test therapeutics to assist the group’s effort to find new medicines to treat neglected tropical diseases.
Tropical diseases, including Lymphatic filariasis, Chagas disease, Leishmaniasis, and Schistosomiasis caused by parasites are responsible for suffering and death disproportionally among those living in poverty. Our group is searching for new medicines that will bring relief to the suffering. In addition to testing compounds we develop, we are collaborating with many groups so that we can test their compounds in our established models. We also work with many groups to screen libraries of compounds against these parasites in an effort to repurpose compounds that were originally made for other diseases, but may inhibit these parasitic diseases because they share a feature of the original target.
Lymphatic filariasis (LF) is caused by three species of thread-like nematode worms, known as filariae – Wuchereria bancrofti, Brugia malayi and Brugia timori. Humans are infected by mosquitos carrying infective stage larvae. The worms make nests in the lymphatic system, which can damage and block the lymphatic vessels, impair the immune system and may cause liver damage. The fluid transfer between blood and tissue is controlled by the lymphatic system and when it is infected with the parasitic worms, the fluid can become trapped in the tissues, which can cause painful swelling and disfigurement commonly known as elephantiasis. In addition to becoming social outcasts due to disfigurement, some people who develop LF become disabled by the physical symptoms of the disease, preventing them from working and bringing more despair. The World Health Organization currently employs an integrative approach to eliminate LF, which includes mass drug administration as well as vector control. However, current drugs are not effective against all stages of the parasite and there is concern that drug resistance by the parasites to current drugs may develop. I test candidate drugs for efficacy against Brugia malayi in a worm assay. We are able to perform high throughput compound screening with a worm assay called the Worminator, which was developed around the computer application “WormAssay” at the CDIPD at UCSF. In addition, we are designing an updated worm box to improve the process.
I also help develop and test models for parasitic disease and test drug candidates for efficacy in these models.
4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection. PLoS Negl Trop Dis. 2017 Dec 27;11(12):e0006132. doi: 10.1371/journal.pntd.0006132. eCollection 2017 Dec. Calvet CM, Choi JY, Thomas D, Suzuki B, Hirata K, Lostracco-Johnson S, de Mesquita LB, Nogueira A, Meuser-Batista M, Silva TA, Siqueira-Neto JL, Roush WR, de Souza Pereira MC, McKerrow JH, Podust LM.
Delayed toxicity associated with soluble anthrax toxin receptor decoy-Ig fusion protein treatment. PLoS One. 2012;7(4):e34611. doi: 10.1371/journal.pone.0034611. Epub 2012 Apr 12. Thomas D, Naughton J, Cote C, Welkos S, Manchester M, Young JA.
Interaction of cowpea mosaic virus nanoparticles with surface vimentin and inflammatory cells in atherosclerotic lesions. Nanomedicine (Lond). 2012 Jun;7(6):877-88. doi: 10.2217/nnm.11.185. Epub 2012 Mar 6. Plummer EM, Thomas D, Destito G, Shriver LP, Manchester M.
Multivalent display of proteins on viral nanoparticles using molecular recognition and chemical ligation strategies. Biomacromolecules. 2011 Jun 13;12(6):2293-301. doi: 10.1021/bm200369e. Epub 2011 May 13. Venter PA, Dirksen A, Thomas D, Manchester M, Dawson PE, Schneemann A.
Detection of carbohydrates and steroids by cation-enhanced nanostructure-initiator mass spectrometry (NIMS) for biofluid analysis and tissue imaging. Anal Chem. 2010 Jan 1;82(1):121-8. doi: 10.1021/ac9014353. Patti GJ, Woo HK, Yanes O, Shriver L, Thomas D, Uritboonthai W, Apon JV, Steenwyk R, Manchester M, Siuzdak G.
Efficient neutralization of antibody-resistant forms of anthrax toxin by a soluble receptor decoy inhibitor. Antimicrob Agents Chemother. 2009 Mar;53(3):1210-2. doi: 10.1128/AAC.01294-08. Epub 2008 Dec 15. Sharma S, Thomas D, Marlett J, Manchester M, Young JA.
A viral nanoparticle with dual function as an anthrax antitoxin and vaccine. PLoS Pathog. 2007 Oct 5;3(10):1422-31. Manayani DJ, Thomas D, Dryden KA, Reddy V, Siladi ME, Marlett JM, Rainey GJ, Pique ME, Scobie HM, Yeager M, Young JA, Manchester M, Schneemann A.
Amiodarone and bepridil inhibit anthrax toxin entry into host cells. Antimicrob Agents Chemother. 2007 Jul;51(7):2403-11. Epub 2007 May 7. Sanchez AM, Thomas D, Gillespie EJ, Damoiseaux R, Rogers J, Saxe JP, Huang J, Manchester M, Bradley KA.
Anthrax toxin receptor 2-dependent lethal toxin killing in vivo. PLoS Pathog. 2006 Oct;2(10):e111. Erratum in: PLoS Pathog. 2008 Oct;4(10).doi:10.1371/annotation/08c1bcf0-da65-4abd-97c7-5df86b1120b5. Scobie HM, Wigelsworth DJ, Marlett JM, Thomas D, Rainey GJ, Lacy DB, Manchester M, Collier RJ, Young JA.
A soluble receptor decoy protects rats against anthrax lethal toxin challenge. J Infect Dis. 2005 Sep 15;192(6):1047-51. Epub 2005 Aug 10. Scobie HM, Thomas D, Marlett JM, Destito G, Wigelsworth DJ, Collier RJ, Young JA, Manchester M.
Lymphotoxin-alpha- and lymphotoxin-beta-deficient mice differ in susceptibility to scrapie: evidence against dendritic cell involvement in neuroinvasion. J Virol. 2002 May;76(9):4357-63. Oldstone MB, Race R, Thomas D, Lewicki H, Homann D, Smelt S, Holz A, Koni P, Lo D, Chesebro B, Flavell R.
Evidence that the hypermutated M protein of a subacute sclerosing panencephalitis measles virus actively contributes to the chronic progressive CNS disease. Virology. 2001 Dec 20;291(2):215-25. Patterson JB, Cornu TI, Redwine J, Dales S, Lewicki H, Holz A, Thomas D, Billeter MA, Oldstone MB.
Disruption of differentiated functions during viral infection in vivo. V. Mapping of a locus involved in susceptibility of mice to growth hormone deficiency due to persistent lymphocytic choriomeningitis virus infection. Virology. 2001 Mar 1;281(1):61-6. Bureau JF, Le Goff S, Thomas D, Parlow AF, de la Torre JC, Homann D, Brahic M, Oldstone MB.
V and C proteins of measles virus function as virulence factors in vivo. Virology. 2000 Feb 1;267(1):80-9. Patterson JB, Thomas D, Lewicki H, Billeter MA, Oldstone MB.
Measles virus infection in a transgenic model: virus-induced immunosuppression and central nervous system disease. Cell. 1999 Sep 3;98(5):629-40. Oldstone MB, Lewicki H, Thomas D, Tishon A, Dales S, Patterson J, Manchester M, Homann D, Naniche D, Holz A.