New Solicitation Focuses on Development of Cellular Immunology Core

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NIAID supports basic research on microbiology and immunology that may lead to the development of vaccines, therapeutics, and medical diagnostics for the prevention, treatment, and diagnosis of infectious and immune-mediated diseases.

NIAID’s Division of AIDS is seeking a partner to operate the Cellular Immunology Core Laboratory, which will conduct, analyze, develop, optimize, and validate cellular immunologic assays for HIV, Simian Immunodeficiency Virus, Mycobacterium tuberculosis, and other pathogens, to be performed on fresh and frozen preclinical samples.

A new request for proposals (RFP) seeks contractors who can do the following:

  • Conduct validated immunological assays using good laboratory practice (GLP)-like processes
  • Perform data analyses
  • Receive, store, catalog, track, and maintain an inventory of the specimens for evaluation
  • Manage, report, and deposit study data
  • Perform project management activities related to contract activities
  • Conduct initial and final transition activities, as needed

The contractor shall use current state-of-the-art technologies, including, at a minimum, ELISPOT, intracellular cytokine staining, flow cytometry, cell sorting, tetramer staining, and other assays to accomplish the technical objectives, and shall incorporate new and optimized technologies for assay development into contract activities when appropriate. Assays shall incorporate appropriate positive and negative controls using reference panels to define background and dynamic range and shall demonstrate reproducibility and consistency.

Additionally, the contractor shall also use state-of-the-art methods to analyze the data generated by the conduct of the assays, which may require different data analysis methods/platforms as appropriate for each type of assay. Data analyses may require generating publication quality figures, when directed by the contracting officer’s representative. Lastly, an independent Quality Assurance Program, not associated with the contract, shall conduct regular inspections to review facilities, equipment, personnel, methods, practices, and records.

Details and Due Date

Read the RFP Cellular Immunology Core Laboratory for complete details.

NIAID anticipates awarding one cost reimbursement, level-of-effort (term) type contract for a 1-year base period plus six 1-year options for a total possible performance period of 7 years, beginning on March 1, 2024.

Proposals are due on March 17, 2023, by 3 p.m. Eastern Time. Submit applications online through NIH’s electronic Contract Proposal Submission (eCPS) site.

Send inquiries to Kimberly Dormer, NIAID’s contract specialist for this opportunity, at kimberly.dormer@nih.gov.

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Seher H. Anjum, M.D.

Section or Unit Name
Translational Mycology Section
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Section/Unit: Location
NIH Main Campus, Bethesda, MD
This Researcher/Clinician’s Person Page
Seher H. Anjum, M.D.
Parent Lab/Program
Laboratory of Clinical Immunology and Microbiology
Program Description

Associate Investigator for Protocol 93-I-0106: Cryptococcosis in Previously Healthy Adults

Background: 

Cryptococcus is a fungus that causes infections most commonly in immunocompromised patients, such as those with AIDS and solid organ transplant recipients and is currently responsible for an estimated 15% of all AIDS-related deaths globally. Within the U.S., approximately 15-20% have no identifiable immune defect and cryptococcal infection in these hosts has a mortality rate of 30-50% despite optimal antifungal therapy.  

The objectives of this protocol can be broadly categorized as: 

  • Characterize the immunologic and genetic mechanisms predisposing to disease acquisition.
  • Understand the post-infectious inflammatory response and distinguish its consequences from those directly due to fungal growth.
  • Management of post-infectious neuro-inflammatory syndromes associated with cryptococcal meningitis 

This protocol recruits patients who have microbiological evidence of cryptococcal neurologic or non-CNS disease (typically pulmonary or bone). Cerebrospinal fluid (CSF) and blood samples collected during clinical care, are used to measure serum and intrathecal cellular and soluble cytokines as well as to perform in-situ immunohistochemistry. Observational data detailing audiological, ophthalmological and neurocognitive deficits in these patients is also recorded. 

We have recently described a post-infectious inflammatory syndrome (PIIRS) associated with cryptococcal meningoencephalitis (CM) which can be best described as a neuro-inflammatory state during which CM patients present with altered mental status (Montreal Cognitive Assessment Score <22/30), auditory deficits and/or vision loss despite having negative CSF fungal cultures after being treated with optimal antifungal therapy. Based on findings in CSF and brain tissue samples, the underlying mechanism behind this phenomenon is related to the intrathecal expansion of both the innate and adaptive immune system, including HLA-DR+ CD4+ and CD8+ lymphocytes and NK cells. In a cohort of 15 previously healthy CM patients, we have been able to demonstrate an improvement in clinical outcomes with pulse corticosteroid therapy for patients with PIIRS and are currently exploring alternative immunomodulatory agents as steroid-sparing therapy for this indication.

Clinical Studies
Selected Publications

Okeagu CU, Anjum SH, Vitale S, Wang J, Singh D, Rosen LB, Magone MT, Fitzgibbon EJ, Williamson PR. Ocular Findings of Cryptococcal Meningitis in Previously Health Adults. J Neuroophthalmol. 2022 Oct 18.

Anjum S, Dean O, Kosa P, Magone MT, King KA, Fitzgibbon E, Kim HJ, Zalewski C, Murphy E, Billioux BJ, Chisholm J, Brewer CC, Krieger C, Elsegeiny W, Scott TL, Wang J, Hunsberger S, Bennett JE, Nath A, Marr KA, Bielekova B, Wendler D, Hammoud DA, Williamson P. Outcomes in Previously Healthy Cryptococcal Meningoencephalitis Patients Treated With Pulse Taper Corticosteroids for Post-infectious Inflammatory Syndrome. Clin Infect Dis. 2021 Nov 2;73(9):e2789-e2798.

Yang DH, England MR, Salvator H, Anjum S, Park YD, Marr KA, Chu LA, Govender NP, Lockhart SR, Desnos-Ollivier M, Chen S, Halliday C, Kan A, Chen J, Wollenberg KR, Zelazny A, Perfect JR, Chang YC, Bennett JE, Holland SM, Meyer W, Williamson PR, Kwon-Chung KJ. Cryptococcus gattii Species Complex as an Opportunistic Pathogen: Underlying Medical Conditions Associated with the Infection. mBio. 2021 Oct 26;12(5):e0270821.

Anjum S, Williamson PR. Clinical Aspects of Immune Damage in Cryptococcosis. Curr Fungal Infect Rep. 2019 Sep;13(3):99-108.

Visit PubMed for a complete publication listing.

Additional Information

Research Networks

CINCH (Cryptococcus Infection Network in non-HIV Cohort)

Training Programs

NIH-Duke Clinical Research Training Program

 

Major Areas of Research
  • Cryptococcal meningitis in previously healthy hosts
  • Post-infectious neuro-inflammatory responses 
  • The use of steroid-sparing, immunomodulatory agents in neuro-inflammation 
     

Seher H. Anjum, M.D.

Farinaz Safavi, M.D., Ph.D.

Assistant Clinical Investigator
Section or Unit Name
NeuroImmunopathogenesis Unit (NIU)
Lab/Program Name
Laboratory of Clinical Immunology and Microbiology
First Name
Farinaz
Last Name
Safavi
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Section/Unit: Year Established
Section/Unit: Location
NIH Main Campus, Bethesda, MD
This Researcher/Clinician’s Person Page
Farinaz Safavi, M.D., Ph.D.
Parent Lab/Program
Laboratory of Clinical Immunology and Microbiology
Program Description

Inborn Errors of Immunity (IEIs) are genetic disorders of the immune system with clinical manifestations of infection and autoinflammatory syndrome. Neurological disorders are one of the common causes of irreversible morbidity and mortality in patients with IEIs. Neuroinflammatory, neuroinfectious and neurodegenerative diseases have been reported extensively in this patient population but the role of immune related gene defects on development, function and immunoregulation of nervous system is still unknown.

The NeuroImmunopathogenesis Unit performs an integrated bench to bedside research to better understand the role of immunodeficiencies in nervous system. Taking a comprehensive approach to evaluate profile and function of immune cells in both blood and cerebrospinal fluid, the most adjacent cells to nervous system, provides valuable understanding about dynamic of immune cells and responses in CNS immune-compartment paving the path to find more targeted therapeutics. By using induced pluripotent stem cell technology, the unit also investigates the role of immune related gene defects in development and function of human neurons and glia to find underlying cellular and molecular pathways in immunodeficient patients with neurological disorders.

Furthermore, rare neuroinfectious, neuroinflammatory and neurodegenerative diseases with atypical clinical features can be a manifestation of immune related gene defects. Our holistic clinical and basic immunology, neuroscience and genetic approach facilitates to better understand the underlying mechanisms of these presentations to clarify diagnosis and treatments of this patients’ complex and often refractory to treatment neurological diseases.

Selected Publications

Lee MH, Perl DP, Steiner J, Pasternack N, Li W, Maric D, Safavi F, Horkayne-Szakaly I, Jones R, Stram MN, Moncur JT, Hefti M, Folkerth RD, Nath A. Neurovascular injury with complement activation and inflammation in COVID-19. Brain. 2022 Jul 5:awac151.

Safavi F, Thome R, Li Z, Wang L, Rasouli J, Ciric B, Zhang GX, Rostami A. A serine protease inhibitor induces type 1 regulatory T cells through IFN-γ/STAT1 signaling. Cell Mol Immunol. 2020 Sep;17(9):1004-1006.

Safavi F, Nath A. Silencing of immune activation with methotrexate in patients with COVID-19. J Neurol Sci. 2020 Aug 15;415:116942.

Safavi F, Thome R, Li Z, Zhang GX, Rostami A. Dimethyl fumarate suppresses granulocyte macrophage colony-stimulating factor-producing Th1 cells in CNS neuroinflammation. Neurol Neuroimmunol Neuroinflamm. 2020 May 5;7(4):e729.

Rasouli J, Ciric B, Imitola J, Gonnella P, Hwang D, Mahajan K, Mari ER, Safavi F, Leist TP, Zhang GX, Rostami A. Expression of GM-CSF in T Cells Is Increased in Multiple Sclerosis and Suppressed by IFN-β Therapy. J Immunol. 2015 Jun 1;194(11):5085-93.

El-Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, Zhang GX, Dittel BN, Rostami A. The encephalitogenicity of T(H)17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol. 2011 Jun;12(6):568-75.

Major Areas of Research
  • Neurological manifestations of primary and acquired immunodeficiency
  • Role of immune related gene defects in neurons and glial cell function
  • The effect of host immune defects on CNS immune-compartment
  • Investigate the role of Inborn Errors of Immunity (IEIs) in patients with atypical neuroinflammatory, neuroinfectious and neurodegenerative diseases

Subash Babu, M.B.B.S., Ph.D.

Pedro H. Gazzinelli Guimaraes, Ph.D.

Jianbing Mu, M.D., Ph.D.

Associate Scientist (Core)
Jianbing Mu, M.D., Ph.D.
Jianbing Mu, M.D., Ph.D.

Major Areas of Research

  • Genetic and epigenetic gene regulations in Plasmodium parasites
  • Molecular biology of malaria pathogenesis

Program Description

  • Parasites genetic diversity and associated phenotypes, such as antimalarial drug resistance and parasites virulence factors
  • Epigenetic and epitranscriptomic modifications in parasite development and identification of novel targets for antimalaria drugs or transmission blocking
  • Development of high-sensitivity assay for Plasmodium infection and others

Biography

Dr. Mu received his M.D. from Shanxi Medical University, China, and his Ph.D. from Saitama Medical School, Japan. He then joined NIAID Division of Intramural Research in 2000 and served as visiting fellow, research fellow, and staff scientist. Now, Dr. Mu is an associate scientist in the office of the Chief of Laboratory of Malaria and Vector Research (LMVR), NIAID. His research mainly focuses on the functional genomics of Plasmodium parasites, including the mechanisms of malaria gene regulation, drug responses, immune evasion, and pathogenesis by applying various approaches, such as genetic mapping and genome-wide association (GWA), genetic manipulation, epigenetic and epitranscriptomic modification. Findings from his research include the genome-wide association study to map the loci associated with P. falciparum resistance to antimalarial drugs, epigenetic regulation of antigenic variation in P. falciparum parasites, epitranscriptomic modification in P. falciparum gene regulations and the development of the high-sensitivity assay for Plasmodium infection.

Dr. Mu serves as the Editorial Board member for journals including Current Genomics, Frontiers in Cell and Developmental Biology, and Journal of Tropical Medicine. Dr. Mu received numerous awards, including NIAID Merit Award and Performance Award.

Publications

Liu M*, Guo G*, Qian P*, Mu J*, Lu B, He X, Fan Y, Shang X, Yang G, Shen S, Liu W, Wang L, Gu L, Mu Q, Yu X, Zhao Y, Culleton R, Cao J, Jiang L, Wellems TE, Yuan J, Jiang C, Zhang Q (2022) 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes.Proc Natl Acad Sci U S A. Mar 1;119(9):e2110713119. doi: 10.1073/pnas.2110713119.

Mu J, Yu LL, Wellems TE (2020) Sensitive Immunoassay Detection of Plasmodium Lactate Dehydrogenase by Inductively Coupled Plasma Mass Spectrometry. Front Cell Infect Microbiol. Jan 11;10:620419. doi: 10.3389/fcimb.2020.620419.

Xiao B, Yin S, Hu Y, Sun M, Wei J, Huang Z, Wen Y, Dai X, Chen H, Mu J, Cui L, Jiang L (2019) Epigenetic editing by CRISPR/dCas9 in Plasmodium falciparum. Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):255-260. doi: 10.1073/pnas.1813542116.

Mu J, Andersen JF, Valenzuela JG, Wellems TE (2017) High-Sensitivity Assays for Plasmodium falciparum Infection by Immuno-Polymerase Chain Reaction Detection of PfIDEh and PfLDH Antigens.J Infect Dis. Sep 15;216(6):713-722. doi: 10.1093/infdis/jix369.

Jiang L*, Mu J*, Zhang Q, Ni T, Srinivasan P, Rayavara K, Yang W, Turner L, Lavstsen T, Theander TG, Peng W, Wei G, Jing Q, Wakabayashi Y, Bansal A, Luo Y, Ribeiro JM, Scherf A, Aravind L, Zhu J, Zhao K, Miller LH (2013) PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum. .Nature. Jul 11;499(7457):223-7. doi: 10.1038/nature12361. 

Mu J, Myers RA, Jiang H, Liu S, Ricklefs S, Waisberg M, Chotivanich K, Wilairatana P, Krudsood S, White NJ, Udomsangpetch R, Cui L, Ho M, Ou F, Li H, Song J, Li G, Wang X, Seila S, Sokunthea S, Socheat D, Sturdevant DE, Porcella SF, Fairhurst RM, Wellems TE, Awadalla P, Su XZ (2010) Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. Nat Genet. Mar;42(3):268-71. doi: 10.1038/ng.528.

View a complete listing of publications on PubMed.

Tools & Equipment

Sanger sequencing (ABI3730xl) and illumina NextSeq 550 System are available for genotyping, DNA sequencing, whole-genome sequencing and RNA-seq etc.

Section or Unit Name
Malaria Genetics Section
Lab/Program Name
Laboratory of Malaria and Vector Research
First Name
Jianbing
Last Name
Mu
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Off
Section/Unit: Year Established
Section/Unit: Location
Rockville, MD
This Researcher/Clinician’s Person Page
Jianbing Mu, M.D., Ph.D.
Parent Lab/Program
Laboratory of Malaria and Vector Research
Program Description
  • Parasites genetic diversity and associated phenotypes, such as antimalarial drug resistance and parasites virulence factors
  • Epigenetic and epitranscriptomic modifications in parasite development and identification of novel targets for antimalaria drugs or transmission blocking
  • Development of high-sensitivity assay for Plasmodium infection and others
  • Multi-omic studies on disease vectors, with a focus on ticks and mosquitoes, aimed at identifying biomarkers and advancing vaccine development
Selected Publications

Lee SK, Crosnier C, Valenzuela-Leon PC, Dizon BLP, Atkinson JP, Mu J, Wright GJ, Calvo E, Gunalan K, Miller LH. Complement receptor 1 is the human erythrocyte receptor for Plasmodium vivax erythrocyte binding protein. Proc Natl Acad Sci U S A. 2024 Jan 30;121(5):e2316304121.

Liu M, Guo G, Qian P, Mu J, Lu B, He X, Fan Y, Shang X, Yang G, Shen S, Liu W, Wang L, Gu L, Mu Q, Yu X, Zhao Y, Culleton R, Cao J, Jiang L, Wellems TE, Yuan J, Jiang C, Zhang Q (2022) 5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes. Proc Natl Acad Sci U S A. Mar 1;119(9):e2110713119.

Xiao B, Yin S, Hu Y, Sun M, Wei J, Huang Z, Wen Y, Dai X, Chen H, Mu J, Cui L, Jiang L (2019) Epigenetic editing by CRISPR/dCas9 in Plasmodium falciparum. Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):255-260.

Mu J, Andersen JF, Valenzuela JG, Wellems TE (2017) High-Sensitivity Assays for Plasmodium falciparum Infection by Immuno-Polymerase Chain Reaction Detection of PfIDEh and PfLDH Antigens. J Infect Dis. Sep 15;216(6):713-722.

Jiang L, Mu J, Zhang Q, Ni T, Srinivasan P, Rayavara K, Yang W, Turner L, Lavstsen T, Theander TG, Peng W, Wei G, Jing Q, Wakabayashi Y, Bansal A, Luo Y, Ribeiro JM, Scherf A, Aravind L, Zhu J, Zhao K, Miller LH (2013) PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum. Nature. Jul 11;499(7457):223-7.

Mu J, Myers RA, Jiang H, Liu S, Ricklefs S, Waisberg M, Chotivanich K, Wilairatana P, Krudsood S, White NJ, Udomsangpetch R, Cui L, Ho M, Ou F, Li H, Song J, Li G, Wang X, Seila S, Sokunthea S, Socheat D, Sturdevant DE, Porcella SF, Fairhurst RM, Wellems TE, Awadalla P, Su XZ. Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. Nat Genet. 2010 Mar;42(3):268-71.

Visit PubMed for a complete publications listing. 

Additional Information

Tools & Equipment

Dr. Mu oversees the Genomics Core, which is equipped with advanced technologies to facilitate a broad spectrum of genomic and multi-omic studies. These include Sanger sequencing using the ABI3730xl, which provides high-throughput and high-accuracy DNA sequencing for genotyping and targeted DNA analysis. The Illumina NextSeq 550 System enables high-throughput next-generation sequencing (NGS), supporting applications such as whole-genome sequencing, RNA sequencing (RNA-seq), and epigenomics. Additionally, the CosMx Spatial Molecular Imager (SMI) facilitates cutting-edge spatial multiomics analysis, allowing for high-resolution spatial profiling of RNA and protein expression in complex tissues. Together, these platforms provide comprehensive tools for exploring genetic, transcriptomic, and spatial molecular data to address a variety of research questions.

Major Areas of Research
  • Genetic and epigenetic gene regulations in Plasmodium parasites
  • Molecular biology of malaria pathogenesis

Clifton Barry III, Ph.D.

Artificial Intelligence (AI)—Integrated Research Facility at Fort Detrick

Artificial intelligence (AI), in its many forms, is applied to infectious disease research at the IRF-Frederick. Primarily focused on medical imaging of preclinical models, state of the art methods are developed, applied to ongoing research and translated to human studies of disease.

Sasisekhar Bennuru, Ph.D.

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