Lecture Overview
In this lecture, Dr. Hooper introduces us to the fascinating world of human gut microbiota; the microorganisms that live within our bodies. Although we may think that most bacteria are harmful, Hooper provides ample evidence that symbiotic gut microbes are important to good human health. Her lab is interested in understanding how the gut microbiota changes during illness or disease and how it influences our ability to fight infections. Using germ-free mice, they were able to demonstrate that a healthy gut microbiota can shape development of the host immune system and provide protection against dangerous infections like salmonella.
In the second part of her talk, Hooper explains how the balance of organisms in the gut microbiota is maintained. By comparing DNA microarray data from normal mice and germ-free mice, Hooper’s lab was able to look for genes induced by the gut microbiota. They identified RegIIIγ, an important protein involved in the protection against pathogenic bacteria. They showed that RegIIIγ forms pore complexes in the membranes of gram-positive bacteria and kills them. In mice and humans, the intestinal epithelium is coated with a layer of mucus. Typically, there is a gap between gut bacteria, which are found in the outer part of the mucus layer, and the epithelial cells. Hooper’s lab showed that RegIIIγ helps to maintain this gap by preventing gram-positive bacteria from colonizing the intestinal epithelial surface. This, in turn, prevents infection of the host.
Speaker Bio
Although she always was interested in science, Lora Hooper’s love for biology started after taking an introductory class at Rhodes College in Memphis, TN where she was an undergraduate. Hooper continued her graduate education in the Molecular Cell Biology and Biochemistry Program at Washington University in St. Louis where she joined Jacques Baenziger’s lab. For postdoctoral training, she stayed at Washington University, in the lab of Jeffrey Gordon, where she began her studies of the interaction between gut bacteria and host cells and discovered that bacteria have the capacity to modify carbohydrates important for cell signaling.
Currently, Hooper is a Professor of Immunology at The University of Texas Southwestern Medical Center and a Howard Hughes Medical Institute Investigator. She has established one of the handful of mouse facilities that have the capacity to breed germ-free mice. Using these mice, her lab explores the symbiotic relationship between a host and its microbiota with the aim of providing insight into human health.
Hooper was a recipient of the Edith and Peter O’Donnell Awards in 2013 and in 2015 she was elected to the National Academy of Sciences.
Learn more about Lora Hooper at http://hooperlab.org/ and http://www.hhmi.org/scientists/lora-v-hooper
http://www.ibiology.org/ibioseminars/mammals-symbiotic-gut-microbes-part-1-lora-hooper.html
Medical and Patient education videos
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Title
Description
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Video interview with patient with an aspergilloma and chronic pulmonary aspergillosis, diagnosed after coughing up blood who later developed azole resistance on voriconazole. Patient History This patient had severe kyphoscoliosis as a child with insertion of spinal rods in early adulthood. She is a life-long non-smoker. She first presented in 2001 with an irritating cough and several treatments with antibiotics failed to alleviate it. After 2 years the cough worsened and she developed a fever. She was investigated but results were inconclusive. She then coughed up large amounts of blood (haemoptysis) and had a very severe bleed which was treated with embolisation and oral tranexamic acid. She continued to cough and produce green sputum and lose weight. Aspergillus precipitin titre was high and she was initially diagnosed with chronic pulmonary aspergillosis with one cavity containing an aspergilloma. Treatment with itraconazole did not alleviate her symptoms (despite adequate blood levels) and she started voriconazole and considerable improvement was seen initially and she gained some weight. She continued voriconazole for 2 years. However her Aspergillus titre remained high and her cough continued. Further tests showed her trough plasma levels of voriconazole to be more than 0.5mg/L, however isolates revealed that her Aspergillus fumigatus was drug resistant to itraconazole, voriconazole and posaconazole. The patient has now commenced amphotericin B therapy. We thank the patient for kindly providing this interview.
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Video Interview with long-term ABPA patient who coughed up large sputum plugs. This patient had several episodes of pneumonia and developed bronchiectasis after diagnosis for a collapsed left lung. She was treated with inhaled corticosteroids and bronchodilators and progressed well. She was later diagnosed with possible ABPA (aspergillus precipitins were negative), after producing a large sputum plug which was positive for aspergillus hyphae. Her main symptoms were severe coughing with production of clear sputum. In December 04 her coughing became very severe and she coughed badly for 7 months. Her treatment was modified to include itraconazole (400mg/day solution- she required a higher dose than normal as she was taking other medication which reduced it’s absorption). 8 weeks later she started very severe bouts of coughing over 3 days – which produced a large number of small mucous plugs, finally a very large plug (resembling a piece of grey chewing gum) was coughed up. After this, the coughing subsided and the patient felt well and a chest X-ray at this time showed a significant improvement with clearing of shadows from the right lower lobe. Itraconazole levels have been reduced to 300mg per day and steroid intake reduced. The patient remained well in July 2007. We thank the patient for kindly providing this interview.
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Video interview with patient with childhood asthma and ABPA, who showed a marked improvement in her ABPA and asthma when she commenced nebulised Amphotericin B. Her medication was changed from itraconazole at this time to allow for her to try for pregnancy. Two types of nebuliser – VentStream and the Pari LC system are discussed in the interview. Her condition is still stable using inhaled amphotericin B. We thank the patient for kindly providing this interview
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Video interview with this patient with childhood asthma and ABPA. After persistent chest infections and continuous steroids and a bad productive cough, Aspergillus was cultured from sputum in 2002. After successfully taking itraconazole, the patient developed peripheral neuropathy (tingling and loss of sensation) in the hands. After stopping itraconazole – persistent chest infections requiring antibiotics and prednisolone were common. The patient at this point had a high IgE level and positive RAST tests. Voriconazole was then prescribed – which has successfully treated the aspergillus infection – no steroids are required and the cough is greatly reduced with the patient feeling well. However an unfortunate side effect of voriconazole has been a photosensitive rash on any exposed skin. Despite using complete sunscreen – the rash continues. The patient is continuing to take voriconazole.
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Video interview with patient JW with childhood asthma and subsequent ABPA, describes his experience with 3 different azole types of antifungal drugs and who showed a marked improvement when taking posaconazole.
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Video interview with Catherine, who developed severe invasive aspergillosis following a kidney transplant. Fortunately, she was successfully treated with antifungal drugs. We thank the patient for kindly providing this interview and Pfizer for supporting the production of this video.
