Center for Integrated Solutions for Infectious Diseases

Given the diverse and heterogeneous nature of infectious diseases, we believe that integrating basic science, clinical dialogue, and innovative technologies to ask fundamental questions about infection will give rise to insights leading to broadly applicable impacts on patient care.

Our Science

Research within CISID involves interdisciplinary efforts to address critical gaps in our understanding of infection. Our research interests span microbiology, immunology, genomics, metabolism, cell biology, chemistry, biochemistry, structural biology, and ecology. By coalescing insights across disciplines to ask overarching questions, we are building a new framework for infectious disease research that is relevant to the infected patient.

Our Science Image

Research Themes

Antimicrobial resistance

The rise in antimicrobial resistance poses a major threat to human health. We seek to unveil the underlying mechanisms of resistance – both pathogen as well as host factors that contribute to resistance evolution – and to devise new strategies to prevent, detect, and treat resistant infections. We are applying a range of methods including computation, genomics, chemical biology and structural biology, for example, to understanding the molecular mechanisms of antibiotic resistance in Neisseria gonorrhea and the evolution of carbapenem resistance in Enterobactericeae (Klebsiella pneumoniae), to develop novel strategies for antibiotic discovery against pathogens such as Mycobacterium tuberculosis, and to uncover the structural basis for herpesvirus resistance to antiviral polymerase inhibitors to guide new strategies for therapeutic development.

Antimicrobial resistance Image

Infection and Metabolism

Infection triggers a cascade of changes in the metabolism of both the host and the microbe, which is integral to the pathogen-host interaction. We seek to understand how pathogens impact and are impacted by the metabolic pathways of their hosts – and vice versa – to determine outcomes of infection. For example, we are studying how alterations in host metabolic pathways play a role in clearance of viruses such as SARS-CoV-2 and intracellular bacteria, exploring the targeting of the pathogen respiratory chain, and characterizing the metabolic changes associated with severe sepsis in patients.

Infection and Metabolism Image

Sepsis

Sepsis is a life-threatening medical condition caused by a dysregulated immune response to infection. It involves a heterogeneous process resulting in variable outcomes ranging from recovery to death and long-term immune paralysis. We are employing immune profiling to understand how an individual’s immune set-point and infection history drive sepsis trajectories. We are performing single-cell transcriptional profiling of the immune response to sepsis in patients to understand the basis for immune dysregulation. Using forward genetics screens, we seek to understand the molecular and cellular immune mechanisms that determine disease severity and that underlie immune sequelae to inform the development of biomarkers and targeted clinical interventions.

Sepsis Image

Infection Immunity

The body’s natural immune defense plays a critical role in combating pathogens. We seek to understand the critical molecular and cellular underpinnings of who is at risk for infection, how the immune system responds to microbes, and how microbes evade these defenses which can inform how to recruit host factors to improve outcomes. For example, we are working to understand how pathogens as diverse as HIV, Neisseria gonorrhoeae, and SARS-CoV-2 evade neutralizing antibody recognition and clearance, which can inform vaccine design. Meanwhile, acute infections can have debilitating long-term consequences, with the mechanisms behind such post-infection sequelae being poorly understood. For example, we are delineating the relationships between Epstein-Barr virus and host B cells to elucidate how EBV infection, latency and reactivation and the ensuing host response to understand any relationship between EBV infection and the pathogenesis of multiple sclerosis.

Infection Immunity Image

Microbiome in infection

From modulating immune responses and inflammation, training immunity, interacting with pathogens, creating dysbiosis, and altering metabolism and pathogen environments, the over 100 trillion microbial cells making up the individual human microbiome likely plays a critical role in infection. We are working, for example, to elucidate microbe-immune interactions and how commensal organisms can educate immunity on the skin or gut, and how their metabolites interact with host immune cells and pathogens to impact immune function and infection outcome.

Microbiome in infection Image

Diagnostics and Biomarkers

We strive to leverage cutting edge technologies based on biological insight to discover novel biomarkers and develop new diagnostic tools that can accurately and rapidly detect disease, predict disease severity, and track disease progression.  For example, we are developing rapid methods for determining antibiotic susceptibility based on pathogen transcriptional responses to antibiotic stress and for diagnosing an infecting pathogen based on the detection of pathogen nucleic acids in infected individuals, as well as identifying host biomarkers from patients to diagnose infection and prognosticate.

Diagnostics and Biomarkers Image