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Rajendra Upadhya

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

Selected Publications


Calcineurin controls the cytokinesis machinery during thermal stress in Cryptococcus deneoformans.

Journal Article Proc Natl Acad Sci U S A · May 27, 2025 Calcineurin is a highly conserved phosphatase that plays a central role in sensing calcium and governing transcriptional, posttranscriptional, and posttranslational signaling networks. Calcineurin is a heterodimer consisting of a catalytic A subunit and a ... Full text Link to item Cite

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

Fluorescence and Biochemical Assessment of the Chitin and Chitosan Content of Cryptococcus.

Journal Article Methods Mol Biol · 2024 The cell wall of the fungal pathogens Cryptococcus neoformans and C. gattii is critical for cell wall integrity and signaling external threats to the cell, allowing it to adapt and grow in a variety of changing environments. Chitin is a polysaccharide foun ... Full text Link to item Cite

Cell wall composition in Cryptococcus neoformans is media dependent and alters host response, inducing protective immunity.

Journal Article Front Fungal Biol · 2023 INTRODUCTION: Cryptococcus neoformans is a basidiomycete fungus that can cause meningoencephalitis, especially in immunocompromised patients. Cryptococcus grows in many different media, although little attention has been paid to the role of growth conditio ... Full text Link to item Cite

Membrane Integrity Contributes to Resistance of Cryptococcus neoformans to the Cell Wall Inhibitor Caspofungin.

Journal Article mSphere · August 2022 The fungal pathogen Cryptococcus neoformans causes up to 278 000 infections each year globally, resulting in up to 180,000 deaths annually, mostly impacting immunocompromised people. Therapeutic options for C. neoformans infections are very limited. Caspof ... Full text Cite

Cryptococcus neoformans Cda1 and Cda2 coordinate deacetylation of chitin during infection to control fungal virulence

Journal Article Cell Surface · December 1, 2021 Chitosan, a deacetylated form of chitin, is required for the virulence of Cryptococcus neoformans. There are three chitin deacetylase genes (CDA) that are essential for chitosan production, and deletion of all three genes results in the absence of chitosan ... Full text Cite

Cryptococcus neoformans Chitin Synthase 3 Plays a Critical Role in Dampening Host Inflammatory Responses.

Journal Article mBio · February 18, 2020 Cryptococcus neoformans infections are significant causes of morbidity and mortality among AIDS patients and the third most common invasive fungal infection in organ transplant recipients. One of the main interfaces between the fungus and the host is the f ... Full text Link to item Cite

Chitosan Biosynthesis and Virulence in the Human Fungal Pathogen Cryptococcus gattii.

Journal Article mSphere · October 9, 2019 Cryptococcus gattii R265 is a hypervirulent fungal strain responsible for the recent outbreak of cryptococcosis in Vancouver Island of British Columbia in Canada. It differs significantly from Cryptococcus neoformans in its natural environment, its preferr ... Full text Link to item Cite

Novel Synthetic Polyamines Have Potent Antimalarial Activities in vitro and in vivo by Decreasing Intracellular Spermidine and Spermine Concentrations.

Journal Article Front Cell Infect Microbiol · 2019 Twenty-two compounds belonging to several classes of polyamine analogs have been examined for their ability to inhibit the growth of the human malaria parasite Plasmodium falciparum in vitro and in vivo. Four lead compounds from the thiourea sub-series and ... Full text Link to item Cite

Cryptococcus neoformans Cda1 and Its Chitin Deacetylase Activity Are Required for Fungal Pathogenesis.

Journal Article mBio · November 20, 2018 Chitin is an essential component of the cell wall of Cryptococcus neoformans conferring structural rigidity and integrity under diverse environmental conditions. Chitin deacetylase genes encode the enyzmes (chitin deacetylases [Cdas]) that deacetylate chit ... Full text Link to item Cite

A fluorogenic C. neoformans reporter strain with a robust expression of m-cherry expressed from a safe haven site in the genome.

Journal Article Fungal Genet Biol · November 2017 C. neoformans is an encapsulated fungal pathogen with defined asexual and sexual life cycles. Due to the availability of genetic and molecular tools for its manipulation, it has become a model organism for studies of fungal pathogens, even though it lacks ... Full text Link to item Cite

Intracellular Action of a Secreted Peptide Required for Fungal Virulence.

Journal Article Cell Host Microbe · June 8, 2016 Quorum sensing (QS) is a bacterial communication mechanism in which secreted signaling molecules impact population function and gene expression. QS-like phenomena have been reported in eukaryotes with largely unknown contributing molecules, functions, and ... Full text Link to item Cite

Induction of Protective Immunity to Cryptococcal Infection in Mice by a Heat-Killed, Chitosan-Deficient Strain of Cryptococcus neoformans.

Journal Article mBio · May 10, 2016 UNLABELLED: Cryptococcus neoformans is a major opportunistic fungal pathogen that causes fatal meningoencephalitis in immunocompromised individuals and is responsible for a large proportion of AIDS-related deaths. The fungal cell wall is an essential organ ... Full text Link to item Cite

Toxoplasma gondii Arginine Methyltransferase 1 (PRMT1) Is Necessary for Centrosome Dynamics during Tachyzoite Cell Division.

Journal Article mBio · February 2, 2016 UNLABELLED: The arginine methyltransferase family (PRMT) has been implicated in a variety of cellular processes, including signal transduction, epigenetic regulation, and DNA repair pathways. PRMT1 is thought to be responsible for the majority of PRMT acti ... Full text Link to item Cite

Cross talk between the cell wall integrity and cyclic AMP/protein kinase A pathways in Cryptococcus neoformans.

Journal Article mBio · August 12, 2014 UNLABELLED: Cryptococcus neoformans is a fungal pathogen of immunocompromised people that causes fatal meningitis. The fungal cell wall is essential to viability and pathogenesis of C. neoformans, and biosynthesis and repair of the wall is primarily contro ... Full text Link to item Cite

Cryptococcus at work: gene expression during human infection.

Journal Article mBio · April 22, 2014 Meningitis is a frequent manifestation of infection due to Cryptococcus neoformans and a major cause of increased morbidity in patients with AIDS. Numerous in vitro gene expression and genetic studies of the fungus have predicted a myriad of genes, pathway ... Full text Link to item Cite

Sulphiredoxin plays peroxiredoxin-dependent and -independent roles via the HOG signalling pathway in Cryptococcus neoformans and contributes to fungal virulence.

Journal Article Mol Microbiol · November 2013 Mechanisms of oxidative stress resistance are crucial virulence factors for survival and proliferation of fungal pathogens within the human host. In this study we have identified and functionally characterized the role of sulphiredoxin, Srx1, in oxidative ... Full text Link to item Cite

Global transcriptome profile of Cryptococcus neoformans during exposure to hydrogen peroxide induced oxidative stress.

Journal Article PLoS One · 2013 The ability of the opportunistic fungal pathogen Cryptococcus neoformans to resist oxidative stress is one of its most important virulence related traits. To cope with the deleterious effect of cellular damage caused by the oxidative burst inside the macro ... Full text Link to item Cite

Response of adipose tissue to early infection with Trypanosoma cruzi (Brazil strain).

Journal Article J Infect Dis · March 1, 2012 Brown adipose tissue (BAT) and white adipose tissue (WAT) and adipocytes are targets of Trypanosoma cruzi infection. Adipose tissue obtained from CD-1 mice 15 days after infection, an early stage of infection revealed a high parasite load. There was a sign ... Full text Link to item Cite

Analysis of the glycoproteome of Toxoplasma gondii using lectin affinity chromatography and tandem mass spectrometry.

Journal Article Microbes Infect · December 2011 Glycoproteins are involved in many important molecular recognition processes including invasion, adhesion, differentiation, and development. To identify the glycoproteins of Toxoplasma gondii, a proteomic analysis was undertaken. T. gondii proteins were pr ... Full text Link to item Cite

Improved techniques for endogenous epitope tagging and gene deletion in Toxoplasma gondii.

Journal Article J Microbiol Methods · May 2011 Toxoplasma gondii is an excellent model organism for studies on the biology of the Apicomplexa due to its ease of in vitro cultivation and genetic manipulation. Large-scale reverse genetic studies in T. gondii have, however, been difficult due to the low f ... Full text Link to item Cite

Isocitrate dehydrogenase is important for nitrosative stress resistance in Cryptococcus neoformans, but oxidative stress resistance is not dependent on glucose-6-phosphate dehydrogenase.

Journal Article Eukaryot Cell · June 2010 The opportunistic intracellular fungal pathogen Cryptococcus neoformans depends on many antioxidant and denitrosylating proteins and pathways for virulence in the immunocompromised host. These include the glutathione and thioredoxin pathways, thiol peroxid ... Full text Link to item Cite

Pair-wise interactions of polymerization inhibitory contact site mutations of hemoglobin-S.

Journal Article Protein J · December 2006 The linkage of pair-wise interactions of contact site mutations of HbS has been studied using Le Lamentin [His-20 (alpha)-->Gln], Hoshida [Glu-43 (beta)-->Gln] and alpha(2)beta (2) (T87Q) mutations as the prototype of three distinct classes of contact site ... Full text Link to item Cite

System for expression of microsporidian methionine amino peptidase type 2 (MetAP2) in the yeast Saccharomyces cerevisiae.

Journal Article Antimicrob Agents Chemother · October 2006 Microsporidia are parasitic protists of all classes of vertebrates and most invertebrates. They recently emerged as important infections in various immunosuppressed and immunocompetent patient populations. They are also important veterinary and agricultura ... Full text Link to item Cite

Two steps in Maf1-dependent repression of transcription by RNA polymerase III.

Journal Article J Biol Chem · February 25, 2005 In Saccharomyces cerevisiae, Maf1 is essential for mediating the repression of transcription by RNA polymerase (pol) III in response to diverse cellular conditions. These conditions activate distinct signaling pathways that converge at or above Maf1. Thus, ... Full text Link to item Cite

Site-specific PEGylation of hemoglobin at Cys-93(beta): correlation between the colligative properties of the PEGylated protein and the length of the conjugated PEG chain.

Journal Article Bioconjug Chem · 2003 Increasing the molecular size of acellular hemoglobin (Hb) has been proposed as an approach to reduce its undesirable vasoactive properties. The finding that bovine Hb surface decorated with about 10 copies of PEG5K per tetramer is vasoactive provides supp ... Full text Link to item Cite

Maf1 is an essential mediator of diverse signals that repress RNA polymerase III transcription.

Journal Article Mol Cell · December 2002 Maf1 is a putative repressor of RNA polymerase (pol) III transcription that is conserved from yeast to humans. Here we show that Maf1 is a common component of multiple signaling pathways in S. cerevesiae that sense changes in the cellular environment and r ... Full text Link to item Cite

Stabilization of D-amino acid oxidase and catalase in permeabilized Rhodotorula gracilis cells and its application for the preparation of alpha-ketoacids*.

Journal Article Biotechnol Bioeng · May 20, 2000 The cellular D-amino acid oxidase (DAAO) and catalase activities of Rhodotorula gracilis were greatly increased upon the treatment of the cells with cetyltrimethylammonium bromide (CTAB). However, these enzymes, slowly leaks out from the permeabilized cell ... Full text Link to item Cite

D-amino acid oxidase and catalase of detergent permeabilized Rhodotorula gracilis cells and its potential use for the synthesis of α-keto acids

Journal Article Process Biochemistry · October 1, 1999 Whole cells of the yeast Rhodotorula gracilis ATCC 26217 exhibited low D-amino acid oxidase (DAAO) and catalase activities due to the membrane permeability barrier for D-amino acids arid hydrogen peroxide (H2O2). The permeability barr ... Full text Cite