School of Medicine
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Manuel R. Amieva
Professor of Pediatrics (Infectious Diseases) and of Microbiology and Immunology
Current Research and Scholarly InterestsMy laboratory studies how bacteria colonize our bodies for long periods of time, and how interactions between bacteria and the epithelial surfaces of the gastrointestinal tract and skin may lead to disease. Epithelial surfaces are the first barrier against infection, but they also where our bodies meet and co-evolve with the microbial world.. Several of our studies have focused on the epithelial junctions as a target for bacterial pathogens. The host epithelium uses its epithelial junctions to form a tight but dynamic barrier with an external surface that is inhospitable to microbial attachment, secretes anti-microbial compounds, and has a rapid rate of self-renewal. The balance in the microbe-epithelial relationship results in silent commensalism or symbiosis; an imbalance results in diseases ranging from acute bacterial invasive disease to chronic ulcers or carcinoma.
Our laboratory has developed novel microscopy applications such as quantitative 3D confocal microscopy, electron microscopy, time-lapse imaging, microinjection and micromanipulation to visualize the interaction of pathogens with epithelial cells in culture and in animal and human tissues. Many of out studies focus on the gastric pathogen Helicobacter pylori, but we have also expanded our investigations to include the intestinal pathogens Listeria monocytogenes and Salmonella enterica, and the skin pathogen and colonizer Staphylococcus aureus. I believe that elucidating how microbes communicate with and alter our epithelial cells at a molecular level will be important for finding novel therapeutic targets to control mucosal colonization and prevent invasive disease.
Using this perspective, we have uncovered several novel concepts of how bacteria colonize and breach our epithelial surfaces. For example, we discovered that Helicobacter pylori target the intercellular junctions, and in particular that the virulence factor CagA affects junction assembly and cell polarity. This confers H. pylori the ability to extract nutrients and grow directly on the epithelial surface. We also found that these properties of CagA have consequences for cellular transformation of the epithelium. For instance, we showed that H. pylori affect the activity and state of epithelial stem cells in the stomach by colonizing the epithelial surface deep in the gastric glands. This gland-associated population is essential for pathological inflammation and hyperplasia in animal models, and confers significant colonization advantages to the bacteria. Our Listeria research uncovered a new mechanism and site where bacteria can breach the gastrointestinal epithelial barrier to invade. We found that Listeria find their receptor for invasion at sites of epithelial senescence, where the epithelial junctions undergo dynamic turnover. To study Salmonella and H. pylori we have developed a human organoid model to study their interactions with human gut epithelium in vitro. To study Staphylococcus aureus pathogenesis, we have developed methods to visualize infection at the scale of a single bacterial microcolony using an organoid culture system of human keratinocytes and fibroblasts that grow into a 3D skin-equivalent. We recently identified several proteins at the eptithelial junctions as host factors involved in the pathogenesis of one of Staphylococcus aureus major toxins.
Jennifer K. Bando
Assistant Professor of Microbiology and Immunology
Current Research and Scholarly InterestsMucosal immunology, innate lymphocytes
Helen M. Blau
Donald E. and Delia B. Baxter Foundation Professor, Director, Baxter Laboratory for Stem Cell Biology and Professor, by courtesy, of Psychiatry and Behavioral Sciences
Current Research and Scholarly InterestsProf. Helen Blau's research area is regenerative medicine with a focus on stem cells. Her research on nuclear reprogramming and demonstrating the plasticity of cell fate using cell fusion is well known and her laboratory has also pioneered the design of biomaterials to mimic the in vivo microenvironment and direct stem cell fate. Current findings are leading to more efficient iPS generation, cell based therapies by dedifferentiation a la newts, and discovery of novel molecules and therapies.
Professor of Pathology and of Microbiology and Immunology and, by courtesy, of Chemical and Systems BiologyOn Leave from 03/01/2023 To 12/31/2023
Current Research and Scholarly InterestsOur lab uses chemical, biochemical, and cell biological methods to study protease function in human disease. Projects include:
1) Design and synthesis of novel chemical probes for serine and cysteine hydrolases.
2) Understanding the role of hydrolases in bacterial pathogenesis and the human parasites, Plasmodium falciparum and Toxoplasma gondii.
3) Defining the specific functional roles of proteases during the process of tumorogenesis.
4) In vivo imaging of protease activity
Associate Professor of Medicine (Infectious Diseases) and of Microbiology and Immunology
Current Research and Scholarly InterestsWe seek to understand how interactions between bacteria, bacteriophages, and the human immune system impact our health and disease. Our goals are to gain insights into the pathogenesis of bacterial infections and to generate novel therapies to improve human health.
Burt and Marion Avery Professor of Immunology, Emeritus
Current Research and Scholarly InterestsWe are intereseted in the interaction between the protozoan parasite Toxoplasma gondii and its mammalian host. We use a combination of molecular and genetic tools to understand how this obligate intracellular parasite can invade almost any cell it encounters, how it co-opts a host cell once inside and how it evades the immune response to produce a life-long, persistent infection.
Associate Professor of Microbiology and Immunology
Current Research and Scholarly InterestsOur research focuses on the identification of host genes that play critical roles in the pathogenesis of infectious agents including viruses. We use haploid genetic screens in human cells as an efficient approach to perform loss-of-function studies. Besides obtaining fundamental insights on how viruses hijack cellular processes and on host defense mechanisms, it may also facilitate the development of new therapeutic strategies.
Professor of Microbiology & Immunology
Current Research and Scholarly InterestsContribution of T cells to immunocompetence and autoimmunity; how the immune system clears infection, avoids autoimmunity and how infection impacts on the development of immune responses.
Wallenberg-Bienenstock Professor and Professor of Bioengineering and of Microbiology and Immunology
Current Research and Scholarly InterestsMy research includes methodology improvements in single particle cryo-EM for atomic resolution structure determination of molecules and molecular machines, as well as in cryo-ET of cells and organelles towards subnanometer resolutions. We collaborate with many researchers around the country and outside the USA on understanding biological processes such as protein folding, virus assembly and disassembly, pathogen-host interactions, signal transduction, and transport across cytosol and membranes.
Laura M.K. Dassama
Assistant Professor of Chemistry and of Microbiology and Immunology
BioLaura Dassama is a chemical biologist who uses principles from chemistry and physics to understand complex biological phenomena, and to leverage that understanding for the modulation of biological processes. Her current research focuses on deciphering the molecular recognition mechanisms of multidrug transporters implicated in drug resistance, rational engineering and repurposing of natural products, and control of transcription factors relevant to sickle cell disease.
Mark M. Davis
Director, Stanford Institute for Immunity, Transplantation and Infection and the Burt and Marion Avery Family Professor
Current Research and Scholarly InterestsMolecular mechanisms of lymphocyte recognition and differentiation; Systems immunology and human immunology; vaccination and infection.
Assistant Professor of Pathology and of Microbiology and Immunology
Current Research and Scholarly InterestsHarnessing the gut microbiome to treat human disease.
Assistant Professor of Pediatrics (Infectious Diseases) and of Microbiology and Immunology
Current Research and Scholarly InterestsMalaria is a parasitic disease transmitted by mosquitos that is a leading cause of childhood mortality globally. Public health efforts to control malaria have historically been hampered by the rapid development of drug resistance. The goal of our research is to understand the molecular determinants of critical host-pathogen interactions in malaria, with a focus on the erythrocyte host cell. Our long-term goal is to develop novel approaches to prevent or treat malaria and improve child health.
Instructor, Microbiology & Immunology - Baxter Laboratory
BioAsuka Eguchi, PhD is an instructor working with Helen Blau, PhD at Stanford University. Her interests lie in understanding how cells sense and respond to genotoxic stress. Currently, she is developing therapeutic strategies to combat heart failure in Duchenne muscular dystrophy. Dr. Eguchi received her BS in Biology at the University of Alabama in Huntsville. As a graduate student, she developed an Artificial Transcription Factor library to interrogate transcriptional networks that control cell fate decisions under the mentorship of Aseem Ansari, PhD. During her postdoctoral research, she discovered that a telomere binding protein can rescue disease phenotypes of Duchenne muscular dystrophy in cardiomyocytes differentiated from patient-derived induced pluripotent stem cells. Dr. Eguchi is also developing gene therapies that address heart failure in Duchenne and Becker patients. She is a recipient of the Translational Research and Applied Medicine Award, the American Heart Association Postdoctoral Fellowship, and Muscular Dystrophy Association Development Grant.
Professor of Medicine (Infectious Diseases) and of Microbiology and Immunology
Current Research and Scholarly InterestsOur basic research program focuses on understanding the roles of virus-host interactions in viral infection and disease pathogenesis via molecular and systems virology single cell approaches. This program is combined with translational efforts to apply this knowledge for the development of broad-spectrum host-centered antiviral approaches to combat emerging viral infections, including dengue, coronaviruses, encephalitic alphaviruses, and Ebola, and means to predict progression to severe disease.
Associate Professor of Bioengineering and of Medicine (Microbiology and Immunology)
Current Research and Scholarly InterestsThe human microbiome is linked to a range of phenotypes in the host, but it remains difficult to test causality and explore the mechanisms of these interactions. Our lab focuses on two research areas that share a common goal of studying host-microbiota interactions at the level of molecular mechanism:
1) Technology development. Much of what we know about biology has been learned by deleting individual genes from mice, worms, flies and yeast. The ability to do single-strain and single-gene deletion in the microbiome would be transformative but does not yet exist. We are developing technology in three areas to make this possible:
Synthetic ecology: There is a pressing need for model systems for the microbiome that are defined, but of an order of complexity that approaches the native state. Key experiments in the field often show that a host phenotype can be transferred to a germ-free mouse via fecal transplant. If these phenomena could be recapitulated with a defined, high-complexity community, then reductionist experiments to probe mechanism would be possible. We are developing the technology required to build highly complex defined communities (100-200 bacterial species), make them stable upon transplantation into mice, and probe their function in vitro and in vivo.
Genetics: It is difficult to probe mechanism without genetics, and genetic tools exist for only ~10% of the bacterial species in the gut and skin microbiome. We are developing technologies that will make it possible to delete and insert genes, and build mutant libraries, in many of the most common bacterial strains in the gut and skin microbiome.
Computation: In previous work from the lab, we have developed computational algorithms that identify small-molecule-producing genes in bacterial genomes. In current work, we are devising algorithms for genome mining that are specific to the microbiome, and new tools for predicting the chemical structures of small molecules from untargeted metabolomics data.
2) Molecular mechanisms. Many of the early findings in microbiome research are correlative or associative. We are applying the tools described above to explore the mechanisms underlying these phenomena:
Small molecules: Our lab has had a long-standing interest in small molecules from the microbiota. These include: 1) host-derived molecules metabolized by the microbiome, like bile acids; 2) characteristic components of the bacterial membrane and cell wall, including LPS and capsular polysaccharides; and 3) hundreds of other diffusible small molecules (e.g., the products of polysaccharide and amino acid metabolism) that are present in the bloodstream at high concentrations. Our work in this area seeks to establish the mechanisms by which these molecules modulate host biology, especially by deleting them one at a time in the background of a complex community; and to discover new microbiome-derived metabolites present in the bloodstream and host tissues.
Ecology of complex communities: Synthetic ecology at the 100+ strain scale is entirely unexplored, and the emergent properties of complex communities are not well understood. Our work in this area seeks to understand basic principles outlined by the following questions: How many meaningful interactions exist in a community of hundreds of strains? What constitutes a niche, molecularly and spatially, and how do strains map to niches? What are the molecular correlates of stability, and how does a community reconfigure in response to a perturbation? How rare or common are stable states, and how predictable is the process by which a consortium will evolve toward a stable state? To what extent do priority effects (early colonists and events) determine the outcome of ecosystem development? Can the results of ecosystem competition be predicted or engineered?
Stephen J. Galli, MD
Mary Hewitt Loveless, MD, Professor in the School of Medicine and Professor of Pathology and of Microbiology and Immunology
Current Research and Scholarly InterestsThe goals of Dr. Galli's laboratory are to understand the regulation of mast cell and basophil development and function, and to develop and use genetic approaches to elucidate the roles of these cells in health and disease. We study both the roles of mast cells, basophils, and IgE in normal physiology and host defense, e.g., in responses to parasites and in enhancing resistance to venoms, and also their roles in pathology, e.g., anaphylaxis, food allergy, and asthma, both in mice and humans.
Assistant Professor of Microbiology and of Bioengineering
BioMatthias Garten, Ph.D., is an assistant professor in the department of Immunology and Microbiology and the department of Bioengineering. He is a membrane biophysicist who is driven by the question of how the malaria parasite interfaces with its host-red blood cell, how we can use the unique mechanisms of the parasite to treat malaria and to re-engineer cells for biomedical applications.
He obtained a physics master's degree from the Dresden University of Technology, Germany with a thesis in the laboratory of Dr. Petra Schwille and his Ph.D. life sciences from the University Paris Diderot, France through his work in the lab of Dr. Patricia Bassereau (Insitut Curie) investigating electrical properties of lipid membranes and protein - membrane interactions using biomimetic model systems, giant liposomes and planar lipid membranes.
In his post-doctoral work at the National Institutes of Health, Bethesda in the laboratory of Dr. Joshua Zimmerberg, he used molecular, biophysical and quantitative approaches to research the malaria parasite. His work led to the discovery of structure-function relationships that govern the host cell – parasite interface, opening research avenues to understand how the parasite connects to and controls its host cell.
Jeffrey S. Glenn, M.D., Ph.D.
Joseph D. Grant Professor and Professor of Microbiology and Immunology
Current Research and Scholarly InterestsDr. Glenn's primary interest is in molecular virology, with a strong emphasis on translating this knowledge into novel antiviral therapies. Other interests include exploitation of hepatic stem cells, engineered human liver tissues, liver cancer, and new biodefense antiviral strategies.
Michael R. Howitt
Assistant Professor of Pathology and of Microbiology and Immunology
Current Research and Scholarly InterestsOur lab is broadly interested in how intestinal microbes shape our immune system to promote both health and disease. Recently we discovered that a type of intestinal epithelial cell, called tuft cells, act as sentinels stationed along the lining of the gut. Tuft cells respond to microbes, including parasites, to initiate type 2 immunity, remodel the epithelium, and alter gut physiology. Surprisingly, these changes to the intestine rely on the same chemosensory pathway found in oral taste cells. Currently, we aim to 1) elucidate the role of specific tuft cell receptors in microbial detection. 2) To understand how protozoa and bacteria within the microbiota impact host immunity. 3) Discover how tuft cells modulate surrounding cells and tissue.