Drug Development for Parasitic Diseases, Molecular Mechanism of Pathogenesis
Assistant Adjunct Professor
Skaggs School of Pharmacy and Pharmaceutical Sciences
My research interests can be categorized into two broad areas: (1) Development of new antimicrobials for parasitic diseases. Amebiasis, giardiasis Primary Amebic Meningoencephalitis (PAM) Acanthamoeba keratitis, caused by the protozoan pathogens Entamoeba histolytica, Giardia lamblia and Naegleria fowleri (brain-eating ameba) and Acanthamoeba castellanii 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. Acanthamoeba keratitis is a painful eye infection that can lead to blindness and occurs in healthy individuals wearing contact lenses.
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, thioredoxin reductase, steroidogenic enzymes in Entamoeba 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 PAM and Acanthamoeba kerititis.
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). Masters of Advanced Studies (MAS) in Clinical Research, UC San Diego (2018).
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); KL2 Award (2016);, Research Topic Editor ("Drug Development for Parasite-induced Diarrheal Diseases"), Frontiers in Microbiology (2014-2017); Research Topic Editor ("Recent Progresses in Amebiasis"), Frontiers in Cellular and Infection Microbiology (2017-2019); Judge Travel Award for the Annual Biomedical Research Conference for Minority Students (ABRCMS) (2017); National Center of Leadership in Academic Medicine (NCLAM), UC San Diego (2018).
Leadership Experience: Director of Amoebozoa Core at the Center for Discovery and Innovation in Parasitic Diseases at UCSD (2015-present); Associate Editor, Frontiers in Microbiology (2017-present); Associate Editor, BMC Infectious Diseases (2018-present).
- Advanced Experimental Methods in Biology (BGGN 271)
- Individual Research for Undergraduates (BISP 199)
- Drugs for Bugs: From High-throughput Technology to New Discovery (WARR 87).
- Problem Based Learning (SOMC 224ABC, SOMC 236AB), Student Research Project (SPPS 210), Course Chair, P2 Co-Curricular Program (SPPS 211B).
- 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 and giardiasis
- Responsible for two successful orphan drug designations by the US FDA auranofin for the treatment of amebiasis and Corifungin for the treatment of PAM
- Probst et al. (2019) Bioactivity of farnesyltransferase inhibitors against Entamoeba histolytica and Schistosoma mansoni. Front Cell Infect Microbiol. 9:180.
- Debnath et al. (2019) Predictors of failure from primary therapy for giardiasis in San Diego: a single institution retrospective review. Pathogens 8:165.
- Kangussu-Marcolino MM et al. (2019) Identification of plicamycin, TG02, panobinostat, lestaurtinib, and GDC-0084 as promising compounds for the treatment of central nervous system infections caused by the free-living amebae Naegleria, Acanthamoeba and Balamuthia. Int J Parasitol Drugs Drug Resist. 11:80-94.
- Shing et al. (2020) The antifungal drug isavuconazole is both amebicidal and cysticidal against Acanthamoeba castellanii. Antimicrob Agents Chemother. 64:e02223-19.
- Escrig et al. (2020) Activity of auranofin against multiple genotypes of Naegleria fowleri and its synergistic effect with amphotericin B in vitro. ACS Chem Neurosci. doi:10.1021/acschemneuro.0c00165.
- Active laboratory collaborations with pharmaceutical company partners such as Takeda, Eli Lilly, Acea Biotech
- Drug susceptibility testing of medically important protozoan parasites
- Experience in drug repurposing, success in FDA orphan drug designations and discovery of a new lead that has entered Phase II clinical trial