Complementary tools for biomedical research

New Approach Methodologies (NAMs)

 

What are NAMs?

New Approach Methodologies (NAMs) include advanced in vitro systems, human cell–based models, organoids, microphysiological systems, computational approaches, and AI-enabled analytics. These tools help researchers answer targeted questions efficiently, explore biological mechanisms, and strengthen study design.

Researchers at the TNBRC have used many of these approaches for years — long before the term “NAMs” became widely used.

 

 

NAMs, NHP Research, and the 3Rs

NAMs support the principles of the 3Rs—Replacement, Reduction, and Refinement, which guide responsible biomedical research.

Replacement: When a validated non-animal method can reliably answer a specific question, it may be used.

Reduction: NAMs can refine hypotheses and study design, reducing the number of animals needed while preserving scientific rigor.

Refinement: NAMs can help improve experimental approaches and animal welfare.

At the TNBRC, animal models, including nonhuman primates (NHPs), remain essential for many areas of biomedical research. Complex biological systems, immune responses, and disease processes often cannot be fully understood without whole-organism models.

For every study, researchers must use the most reliable and scientifically appropriate model available. Model selection and experimental design must be fully justified in grant proposals and in every IACUC protocol, consistent with federal oversight requirements.

NAMs therefore serve as complementary tools that strengthen research programs and help investigators design the most rigorous studies possible.

How NAMs are Used at the TNBRC

 
  • Human iPSC-derived brain organoids. Induced pluripotent stem cells (iPSCs) are adult human cells, such as skin or blood cells, that have been reprogrammed into stem cells capable of developing into many different cell types. Under controlled laboratory conditions, these cells can be guided to form three-dimensional clusters of brain-like tissue called organoids. These models allow researchers to study aspects of human brain biology and disease mechanisms in human cells. (Prasun Datta)
  • In vitro blood–brain barrier (BBB) models. Human brain endothelial cells, astrocytes, and microglia are grown together to recreate key features of the blood–brain barrier in a laboratory system. These models allow researchers to study how pathogens, immune responses, and therapeutic compounds interact with the brain’s protective barrier. (Tracy Fischer; Geetha Parthasarathy)
  • Human cell culture systems. Cultured human cells—including endothelial cells, mast cells, neurons, and other brain cell types—are used to investigate infection, inflammation, and cellular signaling in controlled laboratory environments. (Geetha Parthasarathy; Andrew MacLean)
  • Human microphysiological peripheral nerve systems (“organ-on-chip”). These platforms use living human cells grown in engineered microenvironments that replicate key aspects of tissue structure and function. They can be used to study how viruses or other agents interact with human nerve tissue. (Vicki Traina-Dorge)
  • Human brain slice cultures. Thin slices of post-mortem human brain tissue can be maintained in laboratory conditions to study infection and cellular responses in intact tissue environments. (Geetha Parthasarathy)
  • Organotypic brain tissue slice cultures. Brain tissue slices maintained in culture retain structural features of the original tissue and allow researchers to study cell-to-cell signaling and disease mechanisms in a controlled laboratory system. (Andrew MacLean; Geetha Parthasarathy)
  • In vitro antimicrobial susceptibility testing. Laboratory assays are used to determine how bacteria respond to different antibiotics or combinations of therapies. (Monica Embers)
  • Tick testing for Borrelia. Laboratory testing of ticks can identify the presence of Borrelia, the bacteria that cause Lyme disease. (Monica Embers)
  • Diagnostic development using human samples. Laboratory assays using human serum samples can support the development and evaluation of diagnostic tests. (Monica Embers)
  • Real-time cellular activity monitoring. Specialized laboratory systems measure electrical impedance across cultured cells to track cell attachment, growth, toxicity, and cell death in real time. These approaches can be used to evaluate the biological effects of drugs, toxins, or infectious agents. (Chad Roy; Nick Maness)
  • Barrier function monitoring in cell models. Impedance-based systems can measure changes in cellular barriers, such as blood–brain barrier models, allowing researchers to monitor how infection or inflammation affects barrier integrity. (Andrew MacLean)
  • In silico modeling. Computer-based simulations are used to model biological processes, disease mechanisms, or therapeutic responses. (Amir Ardeshir)
  • Spatial transcriptomics and multi-omics analysis. Advanced genomic and computational tools are used to analyze gene expression, microbiome data, immune responses, and metabolic pathways across tissues and biological systems. (Amir Ardeshir)
  • AI-assisted image analysis. Artificial intelligence–based software can analyze microscopy images to quantify cellular changes and biological processes in research samples. (Andrew MacLean)