Our biological applications focus on how cellular heterogeneity and cell-to-cell communication drive ensemble immune responses in different contexts, ranging from acute infection to cancer. Motivated to push our technologies, test the generality of our findings, and help drive forward several medically-relevant fields, we work and collaborate across an enormous breadth of tissues, organisms, and diseases. From these collective observations, we aim to construct generalizable theoretical models that can be experimentally validated in additional natural or engineered biological systems using existing or to-be-developed tools.

 

 

The immune system plays an important role in regulating homeostatic balance across tissues and individuals in the face of changing and challenging environments. Given the pivotal and outsized impact cell subsets (e.g., rare precocious DCs) can have on ensemble dynamics (e.g., global activation of an antiviral response and deactivation of inflammation), we aim to understand the functional consequences of variation in cellular composition across tissues, as well as how different immune cells adapt to changing environmental conditions.

Motivating questions in the lab include:

  1. How can we perform observational and experimental studies to understand the fundamental units of tissues structure and function?
  2. Can we derive basic principles governing homeostatic and pathogenic immune responses within tissues?
  3. What dictates the evolution of clonal antigen-specific T & B cell responses?

To this end, we are several multiple tissues from multiple organisms across common sources of variation. By examining consistent and unique themes that emerge across these systems, we aim to extract basic principles that govern homeostatic and pathogenic immune responses within tissues. Ultimately, we intend to leverage this information to rationally engineer immune responses (e.g., in vaccines and immunotherapies).

Lab Members Involved

  • Alex K. Shalek
  • Sam Kazer
  • Carly Ziegler
  • José Ordovas-Montañes
  • Marc Wadsworth
  • Sam Allon
  • Sarah Nyquist
  • Travis Hughes

Research Areas

  • Biology
  • Cell Atlas
  • Chemistry
  • Computational Methods
  • Genomics
  • Immunology
  • Medicine
  • R&D
  • Statistics
  • Technology
 

Our immune system collaborates with environment- and diet-dependent commensals to establish and maintain homeostasis, and to defend against pathogenic threats (e.g., viruses, bacteria, fungi). We are interested in understanding the nature and impact of these interactions on host tissues, as well as potential avenues to modulate them for therapeutic or prophylactic ends.

Illustrative questions and areas of study include:

  1. How do microbial composition and byproducts influence cellular differentiation and phenotypic diversity within the gut?
  2. How do pathogens (e.g. HIV and TB) impact target cell phenotypes and overall tissue function in the context of acute and systemic infection?
  3. To what degree can therapeutic intervention (e.g. cART for HIV-1) re-establish homeostatic setpoint (i.e. composition and function)?

We have several projects and collaborations (local and international) actively exploring these and related questions in vaccine design that have both inspired, and take advantage of, some of our unique tools to profile thousands of single cells from limited clinical samples anywhere in the world, and develop clinically relevant hypotheses.

Lab Members Involved

  • Sam Kazer
  • Travis Hughes
  • Carly Ziegler
  • Marc Wadsworth
  • Toby Aicher
  • Shaina Carroll
  • Kellie Kolb
  • José Ordovas-Montañes
  • Alex K. Shalek
  • Aleth Gaillard
  • Sarah Nyquist

Research Areas

  • Biology
  • Computational Methods
  • Genomics
  • Immunology
  • Infectious Disease
  • Medicine
  • Microbiology
  • R&D
  • Statistics
  • Technology
 

A diverse array of mechanisms—including genetic mutations, environmental triggers, and diet—can alter cell function and reduce tissue stability, ultimately leading to malignancy, autoimmunity, or immunodeficiency. By identifying which cells these factors affect and in what ways, we aim to develop targeted therapeutic interventions in areas such as cancer, allergy, and inflammatory bowel disease.

Motivating questions that drive our research include:

  1. How do the coordinated interactions between epithelial and immune populations inform barrier tissue function in the context of homeostasis, inflammation and malignancy?
  2. How can we leverage information across systems to derive a set of unifying principles of cellular ecology in health and disease?

Current projects aim to contrast the cellular microenvironments of healthy, inflamed, and malignant (Tirosh et al., 2016; Patel et al., 2014) tissues to examine inflammation-induced changes and the drivers of malignant transformation, as well as to identify which cells remember prior insult. We are similarly profiling aberrant immune behaviors in immune privileged tissues, such as the nervous systems. As in our host-microbial studies, our goal is to identify common features shared across different immune-related diseases that we can probe further in natural (tissues, models) and engineered (patterned cells and cellular structures, organoids) ensembles.

Lab Members Involved

  • Jay Prakadan
  • Andrew Navia
  • Brittany Goods
  • Alex Genshaft
  • José Ordovas-Montañes
  • Jenna Melanson
  • Shaina Carroll
  • Sam Allon
  • Alex K. Shalek
  • Kellie Kolb
  • Marc Wadsworth
  • Riley Drake
  • Sarah Nyquist

Research Areas

  • Biology
  • Cancer
  • Computational Methods
  • Genomics
  • Immunology
  • Medicine
  • Microbiology
  • R&D
  • Statistics
  • Technology