Cummings School of Veterinary Medicine at Tufts University
area of research:
Advancing models of infectious disease through deep learning and artificial intelligence.
The goals of this fellowship are to 1) Create and use digital pathology tools to understand host-pathogen interactions that cause disease; 2) Extract and quantify image features for quantitative analyses and predictive modelling; 3) Gain an understanding of how machine learning, deep learning, and artificial intelligence apply to modern pathology and biomedical research images; 4) Develop critical thinking, scientific communication, and grant-writing skills. The overarching goal of Dr. Martinot’s laboratory is to understand the bacterial genetics determinants of immune evasion and disease progression in order to design better TB vaccines.
PRIMARY MENTOR:
Amanda J. Martinot, DVM, MPH, PhD, DACVP
The primary mentor is Amanda J. Martinot DVM, MPH, PhD, DACVP, an assistant professor at Cummings School of Veterinary Medicine (CSVM). She is an NIH-funded scientist with a research program on tuberculosis and a board-certified veterinary anatomic pathologist. The overarching goal of her research is to define mycobacterial genetic determinants of host-pathogen interactions at the level of the granuloma to advance tuberculosis vaccine development. She co-directs the Comparative Pathology and Genomics Shared Resource at the Cummings School of Veterinary Medicine. Using novel image analysis tools (such as HALO), multiplex immunofluorescence (t-CyCIF), and spatial transcriptomics (GeoMx), her laboratory aims to generate quantitative data to define the spatial biology and tissue microenvironments that contribute to disease control and progression. She collaborates with human physicians, bioinformaticians, immunologists, pathologists, and oncologists to understand local immune responses and signatures of disease progression in animal models.
MENTOR TEAM:
Bree Aldridge, PhD is an Associate Professor, Tufts University Medical School, Boston, MA. Her research focuses on designing optimized therapies for TB using cell biology and engineering approaches to characterize single-cell determinants of mycobacterial drug tolerance, understand how growth heterogeneity is controlled, and engineer combination therapy to shorten TB drug treatment regimens.
Peter Sorger, PhD Laboratory of Systems Pharmacology (LSP) at Harvard Medical School (HMS; https://labsyspharm.org/) studies the fundamental science underlying the invention of new therapeutics and diagnostics and their testing in humans via clinical trials. The lab specializes in projects that involve collaborations among students, postdocs and faculty with different backgrounds and expertise including patient care, laboratory research, and computational modeling.The lab develops and applies diverse measurement methods, including highly-multiplexed and live-cell microscopy, proteomics and functional genomics combined with mathematical modeling approaches such as dynamical systems analysis, machine learning and artificial intelligence. Faculty, staff, fellows, and students have backgrounds in molecular, cell and systems biology, engineering, computer science, and medicine. Research projects span machine-learning approaches to predicting drug-target interaction, investigating the origins and possible ways to prevent adaptive and acquired drug resistance in solid cancers, inventing new small molecule drugs for chronic and inflammatory pain, investigating mechanisms of chronic infection, and improving the design and interpretation of clinical trials.
Richard Mitchell, MD, PhD is a Professor of Pathology at Brigham and Women's Hospital and Harvard Medical School and Associate Director, Curriculum, Harvard-MIT Health Sciences and Technology, Harvard Medical School. His research focus is cardiac pathology. He actively teaches in the HMS and MIT medical curriculum.
Scott Lovitch, MD, PhD is an Assistant Professor of Pathology at Harvard Medical School and an Associate Pathologist at Brigham and Women’s Hospital and specializes in hematopathology and molecular diagnostic pathology. His research interests include the role of the PD-1 pathway and other coinhibitory pathways in hematologic malignancy, and the development of novel immunohistochemical and molecular diagnostic assays for diagnosis and personalized therapy of hematologic malignancy. He is active in educational leadership and curriculum development at Harvard Medical School, where I am a member of the Academy Center for Teaching and Learning, co-direct the Foundations course for first-year medical students in the Pathways curriculum and the Pathology of Human Disease course (HBTM 200) for graduate students in the Leder Program in Human Biology and Translational Medicine.
Heather Gardner DVM, PhD, DACVIM (Oncology) is an assistant professor at the Cummings School of Veterinary Medicine at Tufts University. Her laboratory efforts center on comparative and translational oncology, using the tumor genome to inform novel therapeutic approaches. She is Co-director of the Comparative pathology and genomics shared resource.
Cheryl London DVM, PhD, ACVIM (Oncology) is a Professor at Cummings School of Veterinary Medicine at Tufts University and the Molecular Oncology Research Institute at Tufts Medical Center. She is Associate Dean for Research and Graduate Education at the Cummings School. She has an active laboratory research program centered on comparative and translational oncology and is involved in the training of graduate students and postdoctoral fellows. She has recently joined the Clinical Trials Office at Cummings School to expand operations and enhance capacity and breadth of trials performed in client owned animals. Dr. London is also an Associate Faculty Professor at the Ohio State University College of Veterinary Medicine (OSU CVM) where she remains Director of the Clinical Trials Office at the CVM and Director of Translational Therapeutics at the Center for Clinical and Translational Sciences, OSU College of Medicine.
Description of Potential Research Projects:
Computer-aided image processing, analysis, deep learning and artificial intelligence are actively being used in medical applications and biomedical research. The field of veterinary anatomic pathology, with support from the American College of Veterinary Pathologists strategic plan, is now exploring and adopting these new technologies (“digital pathology”) to improve data extraction from images used research and diagnostic settings. To our knowledge, this fellowship is the first to actively recruit and support pathologist fellows to train under veterinary pathologists and computer scientists that are currently developing and using deep learning and artificial intelligence to investigate animal models of human infectious disease. This fellowship is open to board-certified veterinary pathologists and board-eligible trainees with a strong interest in learning to use and apply digital pathology to animal models of infectious disease.
Additional Training Opportunities:
Dr. Martinot’s laboratory. Dr. Martinot is a member of the Tufts Levy Center for Integrated Management of Antimicrobial Resistance (CIMAR) and has collaborations with investigators at Tufts Medical Center as part of the Massachusetts Consortium for Pathogen Readiness (MassCPR) for SARS-CoV-2 Pathobiology, at the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, and the Laboratory of Systems Pharmacology at Harvard Medical. The fellow will have the opportunity to be integrated into monthly laboratory meetings and seminar series with collaborating groups.
Laboratory of Systems Pharmacology (LSP) at Harvard Medical School (HMS; https://labsyspharm.org/) studies the fundamental science underlying the invention of new therapeutics and diagnostics and their testing in humans via clinical trials. The lab specializes in projects that involve collaborations among students, postdocs and faculty with different backgrounds and expertise including patient care, laboratory research, and computational modeling . The lab develops and applies diverse measurement methods, including highly-multiplexed and live-cell microscopy, proteomics and functional genomics combined with mathematical modeling approaches such as dynamical systems analysis, machine learning and artificial intelligence. Faculty, staff, fellows, and students have backgrounds in molecular, cell and systems biology, engineering, computer science, and medicine. Research projects span machine-learning approaches to predicting drug-target interaction, investigating the origins and possible ways to prevent adaptive and acquired drug resistance in solid cancers, inventing new small molecule drugs for chronic and inflammatory pain, investigating mechanisms of chronic infection, and improving the design and interpretation of clinical trials.
CTSI Study group on Spatial Multiomics. Spatial transcriptomics, spatial proteomics and spatial multiomics are considered the next frontier in understanding the molecular basis of disease. The development of computational strategies to integrate large and diverse datasets encompassing differential gene and protein expression at the single cell level in spatial context across multiple patients is a contemporary challenge at the forefront of data science and biomedical research. This study group is dedicated to understanding, applying and disseminating spatial multiomics strategies will foster the development and application of this technology though out the Tufts community and will foster collaboration between researchers and clinicians at the Cummings School of Veterinary Medicine, Tufts Medical Center, the Tufts Clinical and Translational Sciences Institute, the Data Intensive Studies Center and the Tufts High Performance Computing Center.
Department of Infectious Disease and Global Health IDGH sponsors monthly journal clubs and work-in-progress seminars as part of existing graduate and signature programs: Masters of Infectious Disease and Global Health, Masters of Conservation Medicine, PhD in Biomedical Sciences, and certificate in International Veterinary Medicine.
Comparative Pathology and Genomics Shared Resource. CSVM was recently awarded a grant from the Massachusetts Life Sciences program to establish a core on campus, which substantially improves capacity to evaluate animal models of infectious disease. The core is directed by co-mentor Dr. Amanda Martinot (MPH, PhD, DACVP) and co-directed by Dr Heather Gardner, DVM, PhD, DACVIM (Oncology) who specializes in genetics. The fellow will participate in all aspects of the core, developing an understanding of equipment, methods, and applications for advanced digital histopathology techniques: tissue cyclic immunofluorescence (t-CyCIF); RNA and DNA spatial profiling; and machine learning/artificial intelligence algorithm development, validation, and application for H&E, IHC, and IF-stained tissues using HALO (Indicalabs) and other image analysis and AI platforms.
Cummings School of Veterinary Medicine. Weekly, monthly, and quarterly seminars at CSVM, Tufts Medical Center, and local partners (i.e., University of Massachusetts Medical Center in Worcester and Harvard School of Public Health) provide a rich scientific and collaborative environment. CSVM has a robust summer research program and seminar series and a dedicated annual Research Day. A fellow with a strong clinical interest can also attend weekly and monthly seminars on clinical topics for small and large animals, and wildlife; weekly histopathology rounds; and monthly “grand rounds” with specialty services (e.g., ophthalmology and neurology).
Tufts University CTSI. Tufts has many opportunities for fellows at Grafton, Medford, and Boston campuses. The CTSI, housed on the Boston campus, provides outstanding resources in translational science education and training. The mission of the CTSI is to accelerate translation of research into clinical care. The CTSI provide support in research design & analysis, research collaboration, clinical studies & trials, informatics, one health and medical devices. They sponsor drop-in sessions and events with a calendar here: https://www.tuftsctsi.org/all-events/201906/. The CTSI also has a K-scholar program at https://www.tuftsctsi.org/education/k-scholar-programs/ and each semester offers interactive seminars and workshops for new and experienced researchers affiliated with Tufts. Currently, there are at least 28 courses to address the need for investigators to operate across disciplines and stages in the translational spectrum, and to equip participants with competencies that can truly advance clinical and translational research.
Rodent Histopathology Core at Harvard Medical School. Candidates will have an opportunity to train with Roderick Bronson DVM, DACVP in laboratory animal pathology, specifically mouse models of carcinogenesis. Dr. Bronson has contributed to over 500 manuscripts on pathology in mouse models of human disease.
Brigham and Women’s Hospital Department of Pathology. Fellows will have the opportunity to interact with MD pathology residents and fellows training in clinical, anatomic, hematopathology, and infectious pathology through Harvard affiliated teaching hospitals.
Contact Information for Interested Potential Trainees:
Amanda J. Martinot, DVM, MPH, PhD, DACVP
Cummings School of Veterinary Medicine