School of Medicine
Showing 321-340 of 13,046 Results
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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. -
Daniel Kwasi Amponsah
Affiliate, Department Funds
BioDr. Daniel Amponsah was born and raised in Loma Linda, California. He graduated with a BS in Biochemistry from Pacific Union College in Northern California and received his MD from Loma Linda University School of Medicine where he graduated AOA. He completed his internal medicine residency at Massachusetts General Hospital and was appointed the Simulation Chief his senior year. He is interested in pursuing an academic career in interventional cardiology with a focus on outcomes and health disparities. Prior research work has explored outcomes in ischemic time in patients with cardiogenic shock and STEMI with Dr. Anthony Hilliard, disparities in the management of aortic stenosis alongside Dr. Sammy Elmariah, defining type 2 MI using coronary CT with Dr. James Januzzi. He is presently engaged in assessing the potential applications of angiography-derived FFR and IMR across various coronary disease syndromes with Dr. Bill Fearon and investigating disparities in advanced structural interventions with Dr. Celina Yong.
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Michael Amylon
Professor of Pediatrics (Hematology/Oncology) at the Lucile Salter Packard Children's Hospital, Emeritus
Current Research and Scholarly InterestsBone marrow transplantation (BMT) is a treatment modality which is being broadly applied to a growing number of disorders. Increasing success with BMT is offering improved survival to pediatric and adult patients with acute leukemia, chronic leukemia, lymphomas, and a variety of solid tumors as well as severe aplastic anemia.
