Our lab’s research centers on host-pathogen interactions of Mycobacterium tuberculosis, the causative agent of Tuberculosis and SARS-CoV-2.

We study:

1. virulence genes that regulate host cellular immune responses
2. immune evasion, and antigenicity of Mtb and understanding how spatial heterogeneity in TB granulomas during vaccination and drug treatment impacts disease progression
3. immunology and pathologic mechanisms of SARS-CoV-2 infection

We use genetic manipulation of Mtb and transposon mutagenesis to identify critical host-pathogen pathways and identify antigens to develop TB vaccines including novel live attenuated vaccines (LAV). Using TnSeq in vaccinated mice we showed that vaccination shifts the genetic requirements for Mtb growth in vivo, with the immunodominant esx locus becoming less required in vaccinated mice (PMID 40404665). Similarly, TnSeq data from the Rubin lab informed our early work leading to the discovery that a critical virulence operon LprG-Rv1410 mediated triacylglycerol transport in the Mtb cell wall (PMID 26751071). We showed that attenuated Mtb lacking this operon is immunogenic and protective in mice when used as a vaccine (PMID 33315936). We are currently funded by the Gates Foundation to develop this strain as a LAV alternative to BCG. 

Our lab also assists in the development and evaluation animal models for infectious disease pathogenesis research. We currently support our Regional Biosafety Laboratory in use of hamster and murine models of SARS-CoV-2 (PMID: 35521761; 38959328), tuberculosis pathogenesis research, and our facility is actively engaged in research developing murine models for avian influenza.

Amanda Martinot, D.V.M., M.P.H., Ph.D., DACVP

Associate Professor

Cummings School of Veterinary Medicine at Tufts University

Dr. Martinot is a veterinarian-scientist and board-certified veterinary pathologist (anatomic) who specializes in animal models of infectious diseases of global health importance such as tuberculosis (TB), HIV, and SARS-CoV-2. With over 15 years of experience in TB biology, her independent research focuses on preclinical animal models for TB vaccine development and the basic immunology and virulence determinants underlying the TB host-pathogen interaction. As a veterinary pathologist, Dr. Martinot has expertise in animal models for infectious disease pathogenesis and drug and vaccine discovery research, with a focus on nonhuman primate infectious disease pathology. Dr. Martinot is also co-director of the Comparative Pathology and Genomics Shared Resource (link) providing specialized histopathology to academic labs and regional biotechnology companies.