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Rajendra Upadhya

Assistant Research Professor of Molecular Genetics and Microbiology
Molecular Genetics and Microbiology

Overview


My research focuses on fungal disease and virulence pathways in the model yeast Cryptococcus neoformans. During my initial training in Dr. Ian Willis' lab at the Albert Einstein College of Medicine, NY, I discovered a novel yeast protein that is a major regulator of RNA polymerase III transcription and consequently affects cell growth and proliferation. Later, I used this expertise to functionally characterize the genome of Toxoplasma gondii, where I created a number of genome-based methodologies to define the Toxoplasma genomeWe are primarily interested in the characterization of fungal cell walls and how they influence fungal virulence and disease. Fungal cell wall biosynthesis and architecture are good targets for creating new antifungals since the cell wall is important for the yeast but missing in the host. We revealed that cell wall chitosan is necessary for maintaining cell wall integrity in Cryptococcus and is also important for fungal virulence by applying several genomic, molecular biology, and cell biology approaches to the Cryptococcus genome.  Chitosan deficient mutants are avirulent in mice due to their good clearance from the host. This efficient clearance from the host is accompanied by the activation of a protective immunological response, which protects the mice from infection with a virulent wild-type strain later on. As a result, one of our primary goals is to better understand the biogenesis of chitosan in C. neoformans and C. gattii. We discovered that C. neoformans and C. gattii have different mechanisms for controlling chitosan synthesis. Cda1 and Cda2 are both engaged in fugal pathogenesis in C. neoformans, however Cda3 is the sole one implicated in C. gattii virulence. We have observed that different growth circumstances influence the amount of chitosan in the cell wall. In mice, these chitosan-deficient wild-type strains induced protective immunity against C. neoformans infection. Interestingly, the nature of the host immune response varied considerably between chitosan deficient mutants and wild-type that have been grown under different conditions to alter their chitosan levels. These mutants and wild-type strains with varied levels of chitosan allow us to explore the mechanisms of protective immunity evoked by C. neoformans cda1Δ2Δ3Δ.

Current Appointments & Affiliations


Assistant Research Professor of Molecular Genetics and Microbiology · 2022 - Present Molecular Genetics and Microbiology, Basic Science Departments

Recent Publications


Immunological correlates of protection mediated by a whole organism, Cryptococcus neoformans, vaccine deficient in chitosan.

Journal Article mBio · August 14, 2024 UNLABELLED: The global burden of infections due to the pathogenic fungus Cryptococcus is substantial in persons with low CD4+ T-cell counts. Previously, we deleted three chitin deacetylase genes from Cryptococcus neoformans to create a chitosan-deficient, ... Full text Link to item Cite

Measuring Stress Phenotypes in Cryptococcus neoformans.

Journal Article Methods Mol Biol · 2024 Cryptococcus neoformans is an opportunistic human fungal pathogen capable of surviving in a wide range of environments and hosts. It has been developed as a model organism to study fungal pathogenesis due to its fully sequenced haploid genome and optimized ... Full text Link to item Cite

Chitosan-Deficient Cryptococcus as Whole-Cell Vaccines.

Journal Article Methods Mol Biol · 2024 Creating a safe and effective vaccine against infection by the fungal pathogen Cryptococcus neoformans is an appealing option that complements the discovery of new small molecule antifungals. Recent animal studies have yielded promising results for a varie ... Full text Link to item Cite
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Recent Grants


Preclinical studies of a Cryptococcus vaccine for AIDS patients

ResearchAssistant Research Professor · Awarded by National Institute of Allergy and Infectious Diseases · 2022 - 2026

ROLE OF CELL WALL INTEGRITY IN ECHINOCANDIN RESISTANCE IN C. NEOFORMANS

ResearchAssistant Research Professor · Awarded by National Institutes of Health · 2022 - 2023

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