Tulane National Primate Research Center
Grant Number: P51OD011104
Research Emphasis/Objectives
The Tulane National Primate Research Center (TNPRC) is heavily focused on infectious disease research, with significant programs in the host innate and adaptive immune response to infection, neurobiology, Lyme disease, diabetes, cardiovascular disease, and other diseases of aging. The TNPRC is the only NPRC that houses a Regional Biocontainment Laboratory (RBL), capable of doing studies in nonhuman primates (NHPs) at biosafety level 3 (BSL-3), including on tuberculosis, SARS-CoV-2, and other BSL-3 agents. Within the RBL, we also have a registered Select Agent Program for high-consequence pathogens and toxins. At present, we have a highly active program in SARS-CoV-2 research in African green monkeys and rhesus macaques that includes model development, therapeutics, and vaccines. In addition, we have access to mouse SARS-CoV-2 models that can be used for studies with the goal of moving into NHP studies.
Current Research
The major areas of infectious disease research at the TNPRC currently are AIDS, Lyme disease, tuberculosis, SARS-CoV-2, additional emerging zoonotic viruses, and biodefense-related agents. Our research programs in all of these areas are diverse, covering pathogenesis, vaccine development, microbicides, and natural history. Most of the research at the TNPRC involves multidisciplinary studies with investigators in several divisions at the TNPRC and collaborators outside the TNPRC. Common to these studies is a focus on disease pathogenesis and on using such findings to inform the development of vaccines, diagnostics, and therapeutics. Additional studies focus on comorbid conditions associated with infectious diseases, including comorbidities, inflammation, and aging.
Services Provided
To Outside Investigators
Tissue specimens, blood, and other bodily fluids are provided when available. Collection, processing, and shipping costs are normally assumed by the requestor.
To Collaborating Scientists
The TNPRC (tnprc.tulane.edu) provides highly integrated clinical and laboratory support for studies using NHPs. This includes a full-time staff of clinical veterinarians and technicians and core services commonly used for our diverse portfolio of research programs, including the following:
- Diagnostic parasitology
- Vector-borne diseases (maintains arthropods that are important for the study of vector-borne diseases)
- DNA microarray and gene expression
- Anatomic pathology
- Clinical pathology
- Molecular pathology
- Confocal microscopy and image analysis
- Flow cytometry
- Cellular immunology
- Virus characterization, isolation, and production
- Pathogen detection and quantification (composed of diagnostics and RT-PCR units performing serological surveillance and nucleic acid detection for pathogens, respectively)
- Infectious disease aerobiology
- Genetics and genome banking
- Vector development and production
Additionally, the TNPRC has a BSL-3 Core and Select Agent Core located within our RBL that can provide comprehensive studies in animal models and in vitro studies requiring biocontainment.
Quality Assurance and Quality Control
The TNPRC offers a strong quality assurance program that provides optimized and validated protocols, standardized operating procedures (SOPs), and oversight management to assure the highest level of rigor and reproducibility.
Core Services in Biocontainment
- Infectious Disease Aerobiology Core (capabilities for bioaerosol characterization and animal infection studies)
- Biocontainment Core (providing technician support to investigators desiring laboratory support services in biocontainment)
- Select Agent registered facility (RBL)
- Active multi-investigator research program in biocontainment, including select agent pathogens
- Large-capacity Animal Biosafety Level 3 (ABSL-3)
Division of Immunology
The Division of Immunology has a significant service commitment to the TNPRC. These service functions can be divided into three major cores:
- Flow Cytometry Core
- Immunology Assay core
- Diagnostic Parasitology and Vector-Borne Infectious Disease Core
Flow Cytometry Core
The Flow Cytometry Core is an integral part of the TNPRC, supporting the research program of several core and affiliate investigators across multiple disciplines and departments at the TNPRC. The core provides analytical flow cytometry services and live cell sorting under enhanced BSL-2+ conditions. Current instrumentation and services include the following:
- Sorting
- BD FACSAria Fusion (5 lasers, 18 colors)
- BD FACSMelody (3 lasers, 8 colors)
- Miltenyi MACSQuant Tyto (3 lasers, 8 colors)
- Analysis
- BD FACSymphony (5 lasers, 28 colors)
- BD Fortessa X-20 (5 lasers, 18 colors)
- MACSQuant 16 (2) (3 lasers, 14 colors)
- BD LSRII (3 lasers, 13 colors)
- Absolute counts
- MACSQuant 16 (2) (3 lasers, 14 colors)
Immunology Assay Core
Evaluation of the immune response is a crucial element in studies of infectious disease and immunologically mediated disease. Knowledge of the basic mechanism and the level of cellular and humoral immune responses (both innate and adaptive) in NHPs can help elucidate humane disease pathogenesis, as well as therapeutic and/or preventative vaccine development. Providing basic immunological assays, developing new assays, and improving existing ones for the evaluation of the immune response in NHPs is one of the major goals for the Immunology Assay Core. Services include the following:
- High-volume PCR-based major histocompatibility complex (MHC) typing assay for 10 alleles of Indian-origin rhesus macaques
- Blood and tissue lymphocyte isolation
- Multicolor staining for flow cytometry acquisitions
- Magnetic cell separation with the Automated RoboSep Cell Separator
- Irradiation of biological samples using a Mark I Model 30 Irradiator
- Body composition scanning using the GE Lunar Prodigy Total Body Fan Beam densitometer (the dual energy X-ray absorptometry [DEXA] scanning on animal subjects can measure bone mass, fat tissue, and muscle mass)
- Consultation on immunological assays of NHP studies
Diagnostic Parasitology and Vector-Borne Infectious Disease Core
The Vector-Borne Infectious Disease component currently produces tick vectors for research on Lyme disease and other tick-borne diseases. All of the developmental stages of the hard tick Ixodes scapularis are made available for research purposes. The laboratory historically maintained mosquitos for research and retains the capability to propagate this vector as well.
The types of services provided include the provision of ticks for—
- Tick-mediated infection
- Capillary feeding of ticks with select pathogens
- Xenodiagnosis
- Collection of tick saliva
The Diagnostic Parasitology component provides diagnostic services to clinical veterinarians and core and affiliate investigators when parasitic diseases are suspected in resident NHPs. Animals from the TNPRC breeding colony are examined regularly for parasites as part of the preventive health program. The diagnostic parasitology laboratory also examines samples from animals entering an experimental protocol, as the presence of parasites may influence clinical results.
The Core provides the broadest service in that it not only assesses animals assigned to specific projects but also colony and quarantine animals. Parasites, such as Strongyloides fuelleborni, which may cause broncho-pneumonia and enteritis, Trichuris trichiura, and Giardia lamblia (also causes of enteritis), may be effectively diagnosed and treated so as to preserve the health of the individual and the colony. The Diagnostic Parasitology laboratory effectively services all of the investigators that hold animal projects at the TNPRC or that receive samples from NHPs housed at the TNPRC.
Types of services include the following:
- Blood parasite detection via microscopic examination of prepared blood smears and quantitative buffy-coat analysis (QBC)
- Intestinal parasite detection via microscopic examination of direct wet mounts, zinc sulfate flotation prepared slides, or parasite-specific assays
Division of Microbiology
The Division of Microbiology provides important services to the TNPRC and its investigators through three core facilities:
- Pathogen Detection and Quantification Core
- Infectious Disease Aerobiology Core
- Virus Characterization, Isolation, and Production Core
Pathogen Detection and Quantification Core
The Pathogen Detection and Quantification Core (PDQC) is essential for maintenance of the specific-pathogen-free (SPF) status in the macaque breeding colonies for surveillance of potential infectious pathogens to maintain the health of the animals. Moreover, the PDQC provides significant support for the research programs of individual investigators. The PDQC is composed of two units: the Diagnostics Unit performs serological surveillance testing for infections with SPF agents and other pathogens, and the RT-PCR Unit performs nucleic acid detection methods specific for a spectrum of potential pathogens.
Examples of services:
- Multiplex Ab-detection
- ELISA assays
- Real-time PCR
- Multiplex PCR
Infectious Disease Aerobiology Core
The Infectious Disease Aerobiology Core (IDAC) focuses on infectious disease aerobiology. This is an important capability for studying the many infectious agents that are transmitted via aerosols and for evaluating the efficacy of translational therapeutic products and protocols that are delivered by aerosols.
Examples of services:
- Controlled aerosol delivery of vaccines and other therapeutics
- Assessing pathogen viability in aerosols
Virus Characterization, Isolation, and Production Core
The Virus Characterization, Isolation, and Production (VCIP) Core provides virological services to TNPRC NIH core and affiliate investigators. The core provides characterized infectious viruses, entire lots of virus when needed for large-scale individual projects, performs titration assays, prepares virus for inoculations, carries out virological assays such as new drug inhibition testing, provides advice to NIH funded investigators on choice of challenge virus for projects, and provides training in virological techniques to investigators. A central function of the core is to provide these essential services and expertise to TNPRC researchers and our affiliate investigators.
Examples of services:
- Providing high-quality stocks of established viruses
- Isolation of novel viruses
- Quantification of virus stocks
Division of Comparative Pathology
Services provided include the following:
- Anatomic pathology, necropsy, and biopsy services
- Clinical pathology
- Tissue-based molecular pathology and imaging services
Pathology service support is provided to TNPRC's clinical veterinary staff as part of our colony surveillance program. The Division also furnishes support in each of these areas to staff scientists within other divisions at the TNPRC, as well as to collaborating scientists from around the world.
The Anatomic Pathology Core encompasses the necropsy and biopsy services of the Division's functions in supporting the health of the colonies, as well as diagnostic research support. The necropsy and biopsy service provides investigators and collaborators at the TNPRC with gross and histopathologic evaluations of organs and tissues for the purpose of understanding pathologic changes either for diseases that spontaneously arise in the colony or in relation to experimental protocols. In addition, the service assists the clinical veterinarians with colony health and management. The necropsy and biopsy service is TNPRC's primary means to survey, identify, and investigate new disease conditions in NHPs. These investigations serve not only to provide further understanding of disease processes in general but also have the potential to identify new models for the study of human disease.
The Clinical Pathology Core provides clinical data for animals involved in specific research projects, as well as colony animals. The laboratory furnishes complete hematology, chemistry, fecal analysis, fluid analysis, urinalysis, bacterial and fungal culture and identification, and cytology support for all TNPRC animals. The Clinical Pathology Core is currently staffed by two medical research specialists and a laboratory supervisor, all three of whom are American Society for Clinical Pathology (ASCP)-registered medical technologists. The primary responsibility of this unit is to perform hematology, clinical chemistry, and bacteriology for the medical care of the animal colony and to support numerous research projects from scientists at the TNPRC and around the world. The service also provides important diagnostic support for the veterinarians in managing the health and well-being of the animals in the colony.
Confocal Microscopy and Molecular Pathology Core
The Confocal Microscopy and Molecular Pathology Core (CMMPC) provides assistance, service, and training for NIH-funded core and affiliate investigators with confocal microscopy, multicolor immunofluorescent staining, in situ hybridization, immunohistochemistry, image analysis, and digital imaging. It is increasingly clear that in situ tissue-based investigations are needed for a variety of research disciplines, including infectious diseases such as AIDS, tuberculosis, biodefense, coronavirus, and other diseases that specifically target certain tissues. The COVID-19 crisis reminds us that a need remains for pathogenesis studies of infectious agents. Further, trained pathologists are required to distinguish tissue resections in lungs, lymph nodes, gut, and various other tissues. These are mission-critical services provided to NIH-funded investigators involving studies of vaccine responses, immunogenicity, viral target cells and reservoirs, mucosal and neonatal immunology, and, more recently, the effects of coronavirus infections. The simultaneous evaluation of normal and diseased tissues by trained pathologists, linked with confocal microscopy, molecular, and immunohistochemical studies, have always been a tremendous strength of faculty in the Division of Comparative Pathology, which is why the CMMPC was established.
Animals
Rhesus macaques (Macaca mulatta) of both Indian and Chinese origin are available. Other species can be obtained. The vast majority of the rhesus macaques are specific-pathogen free (B virus, SIV, SRV, and STLV1 negative).
Contact Information
Tulane National Primate Research Center
18703 Three Rivers Road
Covington, LA 70433
tulane.edu
Principal Investigator
L. Lee Hamm, M.D.
Senior Vice President and Dean
School of Medicine
Resource/Additional Contacts
Jay Rappaport, Ph.D.
Director and Chief Academic Officer
Phone: 985-871-6201
Fax: 985-871-6569
tnprc-director@tulane.edu
Kasi Russell-Lodrigue, D.V.M., Ph.D., DACLAM
Associate Professor of Medicine
Interim Chief Veterinary Medical Officer, Associate Director, Chair of the Division of Veterinary Medicine
Phone: 985-871-6496
kerussel@tulane.edu
Mark Alise, Ph.D.
Senior Associate Director and Chief Operations Officer
Phone: 985-871-6200
malise@tulane.edu