Microbiome Research at Yale

The Crawford laboratory focuses on Metabolism at the Human-Microbe Interface. High-throughput genome sequencing of bacteria (and fungi) has revealed many highly unusual “orphan” biosynthetic gene clusters suspected of synthesizing novel, structurally diverse, and biologically active small molecules. These types of naturally produced molecules often regulate complex interactions with their animal hosts, hold a rich history of being utilized as human drugs, and serve as excellent molecular probes for identifying new drug targets for a wide variety of diseases. Additionally, there are still many novel metabolites of functional relevance in well-characterized animals, such as humans and mice. Using a blend of small molecule chemistry, protein biochemistry, cell biology, and microbiology, the lab exploits the natural interactions between bacteria and animals to discover new molecules with signaling, antimicrobial, immunomodulatory, and anticancer activities. The lab also connects these products to their underlying biosynthetic genes, characterizes the biosynthetic enzymes involved in their construction, and investigates their roles in biology and medicine.

In this context, we address two major biological questions at the host-bacteria interface, one from the microbe perspective and one from the host perspective:

How do bacterial human/mouse microbiome members regulate host responses, such as inflammation, signal transduction, and DNA damage, at the metabolic level?

How do human and mouse immune cells, such as macrophages, rewire immunometabolism in response to microbial insults?

Dr. Vanessa Ezenwa is a Professor of Ecology and Evolutionary Biology at Yale University. She received a BA in Biology from Rice University, and PhD in Ecology and Evolutionary Biology from Princeton University. She completed postdocs at Princeton and the U.S. Geological Survey. Before joining the Yale faculty in 2021, she was a Professor of Ecology and Infectious Diseases at the University of Georgia. Dr. Ezenwa’s research focuses on the ecology and evolution of infectious diseases in wild animal populations, and she studies how within-host interactions between hosts and pathogens translate to larger-scale epidemiological patterns. She has received a National Science Foundation CAREER Award, a Zoetis Award for Veterinary Research Excellence, and a Fulbright Scholar Award. She is also a fellow of the American Association for the Advancement of Science. Dr. Ezenwa mentors undergraduate, graduate, and postdoctoral researchers and served as founding director of the Interdisciplinary Disease Ecology Across Scales (IDEAS) PhD training program at the University of Georgia from 2015-2021.

We study how the microbiota of ticks and mosquitoes influences the transmission of arthropod-borne diseases.

The Flavell lab studies the relationship between the microbiota and the immune system, particularly in the context of human diseases such as IBD, metabolic syndrome and cancer and their mouse models.

Mechanisms of enteric pathogen restriction by the gut microbiota.

Microbiome research in experimental cirrhosis to identify measures to decrease bacterial translocation, a mechanism that leads to systemic inflammation and decompensation in patients with cirrhosis.

Cooperation and competition in the human gut microbiome; role of the gut microbiota in drug metabolism and function.

Our laboratory investigates gene control in Bacteroides thetaiotaomicron, a dominant member of the mammalian gut microbiota.

Our lab is investigating the interplay between human diet, microbiome, genetics, and immune reponses in inflammatory disease.

My lab applies chemical biology to the discovery of enzymes and other proteins whose biochemical activity shapes host-microbe dynamics in the context of gastrointestinal infections and the gut microbiota.

My lab is interested in looking at the effect of the microbiome on responses to biologics and in understanding how the microbiome regulates immune tolerance.

Our research focuses on the structure elucidation and mode of action of small molecules encoded in the human microbiome. We are particularly interested in secondary microbiota metabolites that have been implicated in human cancers.

Applying synthetic biology technologies to engineer clinical and ecological microbiomes.

The Iwasaki laboratory studies the role of microbiome and virome on immunity and inflammatory diseases. Our research showed that signals from the microbiome help optimize the immune response in the respiratory tract against influenza virus infection.

Understanding the role of microbial metabolites in human disease.

Acquisition and maturation of the gut and airway microbiomes in infants with Cystic Fibrosis.

The Konnikova lab is interested in how the microbiome and the associated metabolome regulate immune development and homeostasis at barrier sites.

We are developing a high-throughput cryo-electron tomography (cryo-ET) pipeline for high-resolution structure determination of molecular machines in cells, in order to gain molecular insights into fundamental biochemical processes.

Provenance and authentication of works of art and other forms of cultural heritage.

The Muzumdar Lab is an inclusive team that seeks to understand how genetic alterations cooperate with environmental and host factors to drive the progression of the most recalcitrant cancers in hopes of devising novel strategies for cancer prevention, interception, and therapy. We strive to train the next generation of cancer research scientists in a diverse work environment that fosters belonging and growth. Using sophisticated genetically engineered and dietary models, we are exploring how obesity shapes the intestinal microbiome to drive the development of pancreatic cancer and other obesity-associated cancers.