School of Medicine
Showing 21-30 of 46 Results
Cristina Maria Alvira
Associate Professor of Pediatrics (Critical Care)
Current Research and Scholarly InterestsThe overall objective of the Alvira Laboratory is to elucidate the mechanisms that promote postnatal lung development and repair, by focusing on three main scientific goals: (i) identification of the signaling pathways that direct the transition between the saccular and alveolar stages of lung development; (ii) exploration of the interplay between postnatal vascular and alveolar development; and (iii) determination of developmentally regulated pathways that mediate lung repair after injury.
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.
Kanwaljeet S. Anand
Professor of Pediatrics (Pediatric Critical Care) and of Anesthesiology, Perioperative and Pain Medicine
Current Research and Scholarly InterestsDr. Anand is a translational clinical researcher who pioneered research on the endocrine-metabolic stress responses of infants undergoing surgery and developed the first-ever scientific rationale for pain perception in early life. This provided a framework for newer methods of pain assessment, numerous clinical trials of analgesia/anesthesia in newborns, infants and older children. His research focus over the past 30+ years has contributed fundamental knowledge about pediatric pain/stress, long-term effects of pain in early life, management of pain, mechanisms for opioid tolerance and withdrawal. Current projects in his laboratory are focused on developing biomarkers for repetitive pain/stress in critically ill children and the mechanisms underlying sedative/anesthetic neurotoxicity in the immature brain. He designed and directed many randomized clinical trials (RCT), including the largest-ever pediatric analgesia trial studying morphine therapy in ventilated preterm neonates. He has extensive experience in clinical and translational research from participating in collaborative networks funded by NIMH, NINDS, or NICHD, a track-record of excellent collaboration across multiple disciplines, while achieving success with large research teams like the Collaborative Pediatric Critical Care Research Network (CPCCRN). He played a leadership roles in CANDLE (Condition Affecting Neuro-Development & Learning in Early infancy) and other activities of the Urban Child Institute and UT Neuroscience Institute. More recently, he led the NeoOpioid Consortium funded by the European Commission, which collected data from 243 NICUs in 18 European countries.
Thomas Anthony ("Tony") Anderson
Clinical Professor, Anesthesiology, Perioperative and Pain Medicine
Current Research and Scholarly InterestsMy lab's research focuses on two areas:
1. Focused ultrasound for peripheral nervous system modulation- We are interested in the potential of focused ultrasound to modulate peripheral nerves and improve both acute and chronic pain.
2. Pediatric perioperative outcomes- Our goals are to understand A) how various perioperative pain management strategies affect outcomes in children who undergo surgery and B) whether disparities in the perioperative pain management of children occur.
Associate Professor of Medicine (Infectious Diseases) and, by courtesy, of Epidemiology and Population Health
Current Research and Scholarly InterestsOur laboratory aims to develop and test innovative approaches to the diagnosis, treatment and control of infectious diseases in resource-limited settings. We draw upon multiple fields including mathematical modeling, microbial genetics, field epidemiology, statistical inference and biodesign to work on challenging problems in infectious diseases, with an emphasis on tuberculosis and tropical diseases.
Associate Professor of Pathology
BioMichael Angelo, MD PhD is a board-certified pathologist and assistant professor in the department of Pathology at Stanford University School of Medicine. Dr. Angelo is a leader in high dimensional imaging with expertise in tissue homeostasis, tumor immunology, and infectious disease. His lab has pioneered the construction and development of Multiplexed Ion Beam Imaging by time of flight (MIBI-TOF). MIBI-TOF uses secondary ion mass spectrometry and metal-tagged antibodies to achieve rapid, simultaneous imaging of dozens of proteins at subcellular resolution. In recognition of this achievement, Dr. Angelo received the NIH Director’s Early Independence award in 2014. His lab has since used this novel technology to discover previously unknown rule sets governing the spatial organization and cellular composition of immune, stromal, and tumor cells within the tumor microenvironment in triple negative breast cancer. These findings were found to be predictive of single cell expression of several immunotherapy drug targets and of 10-year overall survival. This effort has led to ongoing work aimed at elucidating structural mechanisms in the TME that promote recruitment of cancer associated fibroblasts, tumor associated macrophages, and extracellular matrix remodeling. Dr. Angelo is the recipient of the 2020 DOD Era of Hope Award and a principal investigator on multiple extramural awards from the National Cancer Institute, Breast Cancer Research Foundation, Parker Institute for Cancer Immunotherapy, the Bill and Melinda Gates Foundation, and the Human Biomolecular Atlas (HuBMAP) initiative.
Justin P. Annes M.D., Ph.D.
Associate Professor of Medicine (Endocrinology)
Current Research and Scholarly InterestsThe ANNES LABORATORY of Molecular Endocrinology: Leveraging Chemical Biology to Treat Endocrine Disorders
The prevalence of diabetes is increasing at a staggering rate. By the year 2050 an astounding 25% of Americans will be diabetic. The goal of my research is to uncover therapeutic strategies to stymie the ensuing diabetes epidemic. To achieve this goal we have developed a variety of innovate experimental approaches to uncover novel approaches to curing diabetes.
(1) Beta-Cell Regeneration: Diabetes results from either an absolute or relative deficiency in insulin production. Our therapeutic strategy is to stimulate the regeneration of insulin-producing beta-cells to enhance an individual’s insulin secretion capacity. We have developed a unique high-throughput chemical screening platform which we use to identify small molecules that promote beta-cell growth. This work has led to the identification of key molecular pathways (therapeutic targets) and candidate drugs that promote the growth and regeneration of islet beta-cells. Our goal is to utilize these discoveries to treat and prevent diabetes.
(2) The Metabolic Syndrome: A major cause of the diabetes epidemic is the rise in obesity which leads to a cluster of diabetes- and cardiovascular disease-related metabolic abnormalities that shorten life expectancy. These physiologic aberrations are collectively termed the Metabolic Syndrome (MS). My laboratory has developed an original in vivo screening platform t to identify novel hormones that influence the behaviors (excess caloric consumption, deficient exercise and disrupted sleep-wake cycles) and the metabolic abnormalities caused by obesity. We aim to manipulate these hormone levels to prevent the development and detrimental consequences of the MS.
HEREDIATY PARAGAGLIOMA SYNDROME
The Hereditary Paraganglioma Syndrome (hPGL) is a rare genetic cancer syndrome that is most commonly caused by a defect in mitochondrial metabolism. Our goal is to understand how altered cellular metabolism leads to the development of cancer. Although hPGL is uncommon, it serves as an excellent model for the abnormal metabolic behavior displayed by nearly all cancers. Our goal is to develop novel therapeutic strategies that target the abnormal behavior of cancer cells. In the laboratory we have developed hPGL mouse models and use high throughput chemical screening to identify the therapeutic susceptibilities that result from the abnormal metabolic behavior of cancer cells.
As a physician scientist trained in clinical genetics I have developed expertise in hereditary endocrine disorders and devoted my efforts to treating families affected by the hPGL syndrome. By leveraging our laboratory expertise in the hPGL syndrome, our care for individuals who have inherited the hPGL syndrome is at the forefront of medicine. Our goal is to translate our laboratory discoveries to the treatment of affected families.