Laboratory for Combinatorial Drug Regimen Design for Resistant and Emerging Pathogens - (a) Overview
The past two years have shown that infectious diseases are global threats, revealing an urgent need to improve
preparedness to combat unknown pathogens. Furthermore, the alarming increase in infections caused by
antimicrobial resistant (AMR; see glossary, below) pathogens in recent years, exacerbated by the COVID-19
pandemic, illustrates that we are also on the verge of losing our ability to treat infections caused by known
pathogens. Combination drug treatment is the therapeutic mainstay in the treatment of infections caused by
several microbial pathogens, including HIV and the tuberculosis bacterium. Still, systematic and efficient
development of such treatments for AMR or emerging pathogens is lacking. Tufts University (TU) is proposing
to construct a new biomedical research facility, the Laboratory for Combinatorial Drug Regimen Design for
Resistant and Emerging Pathogens (LCDRD), to design and develop new combinatorial therapeutic approaches
for bacterial, viral, fungal, and parasitic infections and to accelerate research on AMR and emerging pandemic
pathogens. The LCDRD is designed to facilitate the development of novel treatments for difficult-to-treat
infections due to pathogens from both animals and humans. In addition to generating new therapies for AMR or
emerging pathogens, this facility will provide diverse, well-characterized human bacterial pathogens with linked
clinical data from across ‘Tufts-Medicine’, a state-wide network of hospitals serving diverse populations, for study
by academia and industry. The Stuart B. Levy Tufts Center for Integrative Management of Antimicrobial
Resistance (CIMAR) unites faculty from TU and Tufts Medical Center (TMC), as well as affiliate members from
across the region and nation, with expertise in biomedical research, engineering, human and veterinary
medicine, global health, environmental surveillance, policy, and education, to catalyze the development of new
combinatorial drug strategies to treat a wide range of pathogens. Working with CIMAR in LCDRD will be the
nascent Center for Emerging Infectious Diseases and Response (CEIDAR), which addresses emerging and
expanding infectious disease threats such as insect-borne bacterial and viral pathogens. CEIDAR includes the
Tufts Lyme Initiative and utilizes the BSL-3 level Tufts New England Regional Biosafety Laboratory (NERBL) at
Tufts Cummings School of Veterinary Medicine in Grafton, an important resource for expanding work. Institutions
affiliated with CIMAR/CEIDAR span a spectrum of academic and pharmaceutical interests and, although located
locally at TU, will enhance transdisciplinary interactions among regional and national investigators and entities.
Project Goals: The LCDRD will enable specialized and collaborative work on emerging and resistant microbial
pathogens that is required to generate new combinatorial treatments. The facility will: 1) enhance interaction
between clinicians and biomedical researchers to generate therapeutic antimicrobial drug regimens, particularly
combination therapies, against CDCs urgent and emerging threat pathogens; 2) develop genetic and systems
approaches to facilitate ‘personalized medicine’ for patients with difficult-to-treat infection; 3) provide a space
where visiting scientists can receive hands-on training, allowing knowledge dissemination intra-institutionally,
regionally, nationally, and globally; and 4) increase the national capacity to respond to infectious disease
emergencies by providing academic and industrial entities access to libraries of well-characterized isolates for
emerging pandemic and AMR pathogens.
Affected Space and Requested Equipment: The LCDRD will provide a modern, centralized laboratory and
collaboration capacity for a multi-institutional effort to utilize state-of-the-art research technologies to generate
and characterize novel drug therapies for pathogens resistant to current therapeutic regimens as well as new
pandemic threats. It will provide a specialized and biosecure environment for researchers to work with multi-
drug resistant (MDR) and emerging pathogens. It will be built in an existing 2,400 sq. ft. shell space in the
Biomedical Research and Public Health Building on the Tufts Health Sciences campus in Boston. The new
facility, directly adjacent to Tufts’ existing BSL-3 lab and the laboratories of the PI and a key CIMAR investigator,
will be shared by teams of interdisciplinary researchers from four TU schools and TMC, as well as collaborators
from other regional and national institutions.
Impact on Research and Clinical Practice: The National Health Security Strategy, 2019-2022, states that “the
growing incidence of AMR has both public health and national security consequences” and that “expanding the
antimicrobial arsenal is a real and immediate requirement to avoid an era of untreatable infectious diseases.”
Through centralizing and leveraging our expertise in bacterial, viral, and MDR pathogens, innovative measures
of combinatorial drug efficacy, and deep clinical expertise in treatment-resistant infections, the LCDRD will
support the nation’s AMR crisis response by generating novel therapies, both at Tufts and in collaboration with
other academic and pharmaceutical entities across the country (Fig. 1). LCDRD will be a national center of
excellence that makes broadly available well-characterized pathogens with clinical data, allowing for linkage of
patient outcomes to strain-level pathogenicity and combination therapy. This will enable a true link from bedside
to bench and back—a feedback loop that will maintain a tight translational focus, inform treatment regimens for
current and emerging threats, and promote personalized medicine.
