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Dr. Anjan Debnath

Drug Discovery for Parasitic Diseases

Victor Nizet

Anjan Debnath, Ph.D.

Assistant Adjunct Professor
Skaggs School of Pharmacy and Pharmaceutical Sciences

Email
adebnath@ucsd.edu

Phone
(858) 822-5265


Research Summary: Drug Development for Parasitic Diseases, Molecular Mechanism of Pathogenesis

My research interests can be categorized into two broad areas: (1) Development of new antimicrobials for parasitic diseases. Amebiasis, giardiasis and Primary Amebic Meningoencephalitis (PAM), caused by the protozoan pathogens Entamoeba histolytica, Giardia lamblia and Naegleria fowleri (brain-eating ameba) continue to be the major causes of morbidity and mortality. Colitis and diarrhea are the most common manifestations of amebiasis and giardiasis and PAM contributes to extensive inflammation and hemorrhage of the brain. My research on drug discovery uses a two-pronged approach, combining a strategy of repurposing compounds that are already in clinical development along with development of compounds with novel scaffolds and improved activity against the parasites. This approach encompasses both robotic-driven technology and close interaction with multiple academic groups, pharmaceutical company partners and non-profit organizations. This aligns well with the mission of the Center for Discovery and Innovation in Parasitic Diseases (CDIPD), which is to discover and develop drugs for neglected parasitic diseases.

(2) Studies on molecular mechanism of pathogenesis. Both E. histolytica and N. fowleri are remarkable organisms with phagocytic and proteolytic capabilities, invading colonic mucosa and human brain. We are using these model systems to identify or validate key virulence factors contributing to colonic and brain infections. In addition, we are using designed small molecule inhibitors to probe the function of important proteins, such as cysteine protease and heat shock protein 90, in Entamoeba and Naegleria biology. These studies are providing important new clues about how a pathogen orchestrates responses to the host environment and the knowledge generated in these studies has the potential for generating new types of therapeutics for the treatment of amebiasis and PAM.

Academic Achievements

Education:B.Sc. (Hons.) in Zoology, University of Calcutta, India (1995); M.Sc. in Zoology, University of Calcutta, India (1997); Ph.D. in Parasitology, National Institute of Cholera and Enteric Diseases, University of Calcutta, India (2005).

Awards and Honors: Lady Tata Memorial Trust Junior Scholarship, India (1998); UNESCO-American Society for Microbiology Travel and Scholarship Award (2002); Bill & Melinda Gates Foundation Keystone Symposia Scholarship (2012); Finalist for the 2012 Deloitte QB3 Award for Innovation; Honorary Sage Scholar, Sage Bionetworks (2016); Guest Associate Editor, Research Topic Editor (“Drug Development for Parasite-induced Diarrheal Diseases”), Frontiers in Microbiology; KL2 award (2016).

Leadership Experience: Director of Amoebozoa Core at the Center for Discovery and Innovation in Parasitic Diseases at UCSD (2015-present).

Key Contributions to Pharmaceutical Sciences

  • Developed a shotgun genomic DNA microarray for E. histolytica
  • Developed high-throughput screening assays for E. histolytica and Naegleria
  • Discovered a new lead, auranofin, for the treatment of amebiasis and a new lead, Corifungin, for the treatment of Primary Amebic Meningoencephalitis
  • Auranofin has entered a Phase II clinical trial for amebiasis
  • Responsible for two successful orphan drug designations by the US FDA auranofin for the treatment of amebiasis and Corifungin for the treatment of PAM

Selected Recent Publications (View More)

Debnath et al. (2013)Reprofiled drug targets ancient protozoans: drug discovery for parasitic diarrheal diseases. Gut Microbes. 4(1):66-71.

Debnath et al. (2014) In Vitro Efficacy of Corifungin against Acanthamoeba castellanii Trophozoites and Cysts. Antimicrob Agents Chemother. 58(3):1523-8.

Debnath et al. (2014) Hsp90 inhibitors as new leads to target parasitic diarrheal diseases. Antimicrob Agents Chemother. 58(7):4138-44.

Shahinas et al. (2015) Heat shock protein 90 inhibitors repurposed against Entamoeba histolytica. Front Microbiol. 6:368.

Jarrad et al. (2016) Nitroimidazole carboxamides as antiparasitic agents targeting Giardia lamblia, Entamoeba histolytica and Trichomonas vaginalis. Eur J Med Chem. 120:353-362.

Potential Collaborative Programs with the Pharmaceutical Industry

  • Active laboratory collaborations with pharmaceutical company partners such as Eli Lilly, Acea Biotech
  • Experience in drug repurposing, success in FDA orphan drug designations and discovery of a new lead that has entered Phase II clinical trial