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:

1. Diagnostic parasitology
2. Vector-borne diseases (maintains arthropods that are important for the study of vector-borne diseases)
3. DNA microarray and gene expression
4. Anatomic pathology
5. Clinical pathology
6. Molecular pathology
7. Confocal microscopy and image analysis
8. Flow cytometry
9. Cellular immunology
10. Virus characterization, isolation, and production
11. Pathogen detection and quantification (composed of diagnostics and RT-PCR units performing serological surveillance and nucleic acid detection for pathogens, respectively)
12. Infectious disease aerobiology
13. Genetics and genome banking
14. 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:

1. Flow Cytometry Core
2. Immunology Assay core
3. 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:

1. Pathogen Detection and Quantification Core
2. Infectious Disease Aerobiology Core
3. 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.

Anatomic Pathology Core

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.

Clinical Pathology Core

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

Grant Number: P51OD011132

Research Emphasis/Objectives

The Emory National Primate Research Center conducts essential basic science and translational research to discover causes, preventions, treatments, and cures to help people across generations and the world live longer, healthier lives.

Current Research

Behavioral Neuroscience and Psychiatric Disorders

The mission of the Division of Behavioral Neuroscience and Psychiatric Disorders (BNPD) is to conduct basic and translational research to better understand the neurobiological mechanisms underlying behaviors relevant to developmental and psychiatric conditions, such as autism spectrum disorders (ASDs), anxiety-related disorders, depression, and addiction vulnerability. BNPD faculty members use state-of-the-art neural circuit–level approaches to make rapid discoveries in rodent models that can then be translated to nonhuman primate (NHP) models and humans, with the ultimate goal of translating these discoveries into novel treatment strategies to improve mental health. Techniques division researchers use include electrophysiology, epigenetics, chemogenetics (DREADDs), optogenetics, and CRISPR genome editing.

Developmental and Cognitive Neuroscience

Researchers in the Emory Division of Developmental and Cognitive Neuroscience (DCN) examine the neurobiology of social and emotional behavior, and cognition across the life span, providing NHP models for various neuropsychiatric disorders. These include stress-related and neurodevelopmental disorders, such as anxiety, depression, substance use disorder, schizophrenia, ASD, attention-deficit/hyperactivity disorder (ADHD), Alzheimer's disease, and obesity. Additionally, researchers investigate the comparative aspects of cognitive functions, such as memory and language. Faculty members use state-of-the-art technology (behavior, cognition, genomics, brain transient activation/inactivation, and neuroimaging, including PET) to manipulate neurobiology and capture resulting changes in complex social, emotional, and cognitive behavior. Division researchers carry out studies at both of the Center’s locations: the Main Center on Emory’s campus in Atlanta, GA, and the Field Station in Lawrenceville, GA.

Microbiology and Immunology

The Emory Division of Microbiology and Immunology provides leadership, resources, and training to advance molecular and biological approaches to understand, prevent, and treat infectious diseases. By using NHPs and rodents to study the progression of disease and to test new approaches to prevent and treat these infections in the most relevant animal models, Emory scientists provide the basic biomedical research that eventually will result in novel strategies for treatment and prevention of infectious diseases in humans. Current research in the Division of Microbiology and Immunology focuses on vaccines and treatments for HIV and AIDS, pathogenesis of immunodeficiency virus infections in NHPs, comparative AIDS research, immunopathogenesis of hepatitis C virus, studies of novel candidate vaccines for Zika virus, and group A Streptococccus infections.

Neuropharmacology and Neurological Diseases

Researchers in the Emory Division of Neuropharmacology and Neurologic Diseases are working to advance the understanding of the active human brain through studies focusing on the development and function of the nervous system, as well as anatomical differences seen when neurological disorders are present. Faculty in the Division use interdisciplinary approaches in NHP models to study a variety of translational problems in neuroscience, including neurodegenerative diseases (Alzheimer's, Parkinson’s, Huntington’s), basal ganglia and motor function, neurobiology of stroke and epilepsy, and evolutionary biology. Our long-term goal is to develop the knowledge necessary for improved treatment of specific neurological and psychiatric disorders.

Pilot Projects

The Emory National Primate Research Center provides pilot project research awards that provide 1 year of support for up to $70,000 in direct costs. Although the awards are open to all investigators, ORIP guidelines require the direct involvement of an Emory Core Scientist. Emory especially encourages applications from researchers outside the Center, early-career investigators, and those new to the use of nonhuman primates (NHPs) in research, as well as applications that propose translational research projects. The research projects are judged on their potential to generate high-impact preliminary data that will result in research project grants from outside sources and in peer-reviewed publications. Additionally, they must follow ORIP guidelines.

Services Provided

To Outside Investigators

As one of seven National Primate Research Centers (NPRCs), Emory provides specialized scientific resources, expertise, and training opportunities for work with NHPs. Researchers interested in conducting work at the Center must submit a Study Intent Questionnaire. To request the questionnaire, please send an email to [PENDING]. Emory staff is available to assist collaborating researchers with research proposals, budgets, and funding requests.

Animals

• Rhesus macaque (Macaca mulatta)
• Cynomolgus macaque (M. fascicularis)
• Sooty mangabey (Cercocebus atys)
• Squirrel monkey (Saimiri sciureus)
• Chimpanzees (Pan troglodytes)

Service Cores

• Biomarkers Core
• Comparative AIDS Core
• Nonhuman Primate Genomics Core
• Tetramer Core
• Virology Core
• Emory Imaging Core

Scientific Resources

• NPRC Research and Capabilities Inventory Website
• Biological Material Procurement Program
• Center for AIDS Research (CFAR)
• Clinical Resources
• Emory Vaccine Center
• Nonhuman Primate DNA Bank
• Transgenic Huntington's Disease Monkey Resource (THDMR)
• Morris K. Udall Center of Excellence for Parkinson's Disease Research

Contact Information

Emory National Primate Research Center
Emory University
954 North Gatewood Road, NE
Atlanta, GA 30329
enprc.emory.edu
nprc.org
@NPRCnews

Principal Investigator

Ravi I. Thadhani, M.D., M.P.H.
Executive Vice President for Health Affairs, Emory University
Executive Director, Woodruff Health Sciences Center

Director

R. Paul Johnson, M.D.
Center Director
Phone: 404-727-7707
rpaul.johnson@emory.edu

Overview

The primary goal of the National Primate Research Center (NPRC) program is to facilitate the effective use of nonhuman primates (NHPs) by scientists engaged in biomedical research. The NPRC program complements and enables the missions of the other NIH Institutes and Centers (ICs) by providing the animals, facilities, expertise, and resources required to enable NHP research in specific disease areas. ORIP’s Division of Comparative Medicine (DCM) funds seven NPRCs, which are centralized facilities in various parts of the country and are available to investigators on a national basis. Individual NPRCs have specific areas of emphasis, but each is expected to provide a variety of services both individually and through inter-NPRC collaborations to a wide range of investigators. The majority of researchers who use the NPRC physical and intellectual infrastructure are funded by the U.S. Public Health Services, particularly NIH ICs. The NPRCs also support research funded by other federal agencies, non-profit foundations, and the private sector. Each NPRC has a Pilot Research Program, which is advertised nationally and available to investigators who propose the use of NHPs in developmental projects in biomedical research or for studies enhancing the welfare or husbandry of NHPs. For additional information on the seven NPRCS, see the links below or visit the NPRC Research and Capabilities website. Additional information is available on NPRC Access Criteria and Procedures.

NPRC Access Criteria and Procedures

NPRC facilities and resources enable NPRC staff scientists and investigators from the host institution and others across the country to collaborate on their research projects. The centers' specialized resources are intended to support investigators who receive their primary research project funding from NIH, but they also may be used by investigators who are funded by other federal, state, and local agencies, as well as by research foundations and the private sector.

Each NPRC has a Visiting Scientist Program that offers advanced training and research in NHP biology. Collaborative arrangements between investigators and center scientific staff are encouraged and can be developed on studies related to major human diseases, subject to the availability of resources. NHP blood samples, organs, and biological fluids are available through the NPRCs. The following standardized criteria and procedures have been implemented at each NPRC to facilitate utilization of center resources:

Access Criteria

• The nature and scope of the proposed research must be best conducted with NHPs and be compatible with available center resources.
• The proposed research must have high scientific merit as determined by peer review.
• NIH-funded research takes precedence over research activities funded by other sources.
• Grants must contain appropriate budgets for the NPRC portion, including animal per diem costs.
• Availability of NPRC resources, including animals, space, research services and support, and special requirements—such as biosafety facilities—are also limiting factors that must be considered by the investigator.
• Because of potential contamination (e.g., viral, microbial), movement of animals into or out of the NPRC facilities is not allowed. Thus, the proposed research using live animals must use NPRC animals, and the research must be conducted at the NPRC.

Access Procedures

• An initial research proposal must be submitted by the researcher to the NPRC prior to submitting an application for funding. The director then consults with the research services, veterinary, and colony management staff members at the center to assess resource availability and project feasibility.
• When resource availability and project feasibility have been established, the NPRC staff will provide budget information to the researcher regarding the center costs to be included in the formal research proposal.
• The scientific merit of the proposal must then be evaluated through the NIH peer review process or through a similar process at other agencies. However, small pilot projects with other funding sources may be considered. In the latter case, the peer review is conducted by the NPRC Research Advisory Committee.
• In addition to the scientific peer review, a protocol approved by the Institutional Animal Care and Use Committees (IACUC) at both the investigator's institution and the NPRC must be in place. Protocols must also be established to address biosafety concerns.
• When the investigator has received notification of funding, the NPRC director or designee should be advised immediately so that the resources at the center may be reserved for the funded proposal.
• Biological materials, such as blood samples, organ tissues, and biological fluids, can be obtained by contacting the appropriate staff at the NPRCs.

All publications resulting from research conducted at or with NPRC resources must bear an appropriate acknowledgment of ORIP support, including the P51 base grant number.

Inquiries

For additional information about the Visiting Scientist Program and resources available at a specific center, including applying to utilize a center's resources, contact the center director or appropriate contact person listed in this directory.