Manuel Amieva, MD, PhD

Associate Professor

Current Research and Scholarly Interests My laboratory studies the strategies pathogens utilize to colonize and subvert the epithelial barrier. We have focused on the epithelial junctions as a target for bacterial pathogens, since the cell-cell junctions serve as both a barrier to infection and also a major control site for epithelial function. In particular, we are interested in how the gastric pathogen Helicobater pylori may cause cancer by interfering with cell signaling at the epithelial junctions. We are also studying how various bacteria cross and invade the epithelium. For example, we recently found that Listeria monocytogenes targets a specialized subset of cell-cell junctions at the tip of the intestinal villi to find its receptor for invasion. We are interested in determining whether this mode of gastrointestinal invasion of the epithelium is also used by other gastrointestinal pathogens.  

Ann Arvin, MD

Professor

Current Research and Scholarly Interests Varicella-zoster virus (VZV) causes varicella (chickenpox) and zoster (shingles). Our laboratory investigates the molecular virology of VZV, focusing on the functional roles of particular viral gene products in pathogenesis and virus-cell interactions in differentiated human cells in SCID mouse models of VZV infection in vivo. Aspects of VZV tropism are investigated using SCID mice that have human skin, T cell and dorsal root ganglion xenografts and VZV recombinant viruses that have targeted mutations of viral promoters, open reading frames and non-coding regions. The consequences of targeted mutations in the VZV genome reveal functions that are important for VZV pathogenesis and that counteract intrinsic cellular regulation of VZV replication. These studies provide information relevant for developing new genetically engineered vaccines to reduce the disease burden of VZV infections.

Sharon F. Chen, MD, MS

Clinical Associate Professor

Current Research and Scholarly Interests

My research interest is in viral infections commonly affecting immunocompromised patients, investigating the pathogenesis and anti-viral immunity of these “opportunistic” viruses. I have a special interest in latent and persistent viruses, such as CMV and BK virus, in solid organ transplant patients. I focus on the host immune response to these viral infections with the end goal of improving clinical practices. I collaborate with both individual and core viral and immunology laboratories to conduct my research. As Co-director of the Pediatric Infectious Diseases Program in Immunocompromised Hosts, I have a research interest in developing and conducting clinical studies to improve identification, treatment and prevention of infectious diseases in the immunocompromised patient population. I also have a scholarly interest in establishing best practices for these patients. My scholarly work extends to medical education. I am the Co-Chair for a multi-institution microbiology and immunology curriculum development project (with the Robert Wood Johnson Foundation) that aims to re-imagine how medical students gain knowledge in medical school. We are pursuing an innovative approach that involves concepts of the “flipped” classroom. We will be studying the short and long-term outcomes of students who learn from our innovative approach compared to the current standard approach.

Despina Contopoulos-Ioannidis, MD

Clinical Associate Professor

Current Research and Scholarly Interests My research interests are in the following areas: A) Development of guidelines for the management and prevention of congenital Toxoplasmosis in the U.S.; B) Epidemiology of Toxoplasmosis in the U.S. with particular interest in outbreaks of acute Toxoplasmosis within families; C) Exploration of the hypothesis of antibiotic-associated weight gain effect in children and adolescents analyzing population cohort data from large primary care organizations; D) Empirical evaluations of the strengths and limitations of the globalization of pediatric clinical research; E) Appraisal of the cost-effectiveness analyses studies of childhood vaccinations; F) Patient-safety related projects in children through population-level analyses of large databases such as the OSHPD database of California hospitalizations, as well as through empirical evaluations of strategies to decrease diagnostic errors in clinical practice; and G) Evidence-based medicine with particular focus in Pediatrics. As an affiliated faculty member of the Meta-Research Innovation Center at Stanford (METRICS), I am involved in several meta-epidemiologic research projects including empirical evaluations of the comparative effectiveness and/or comparative safety of medical interventions in diverse populations (e.g., adult versus pediatric), settings (e.g., more versus less developed countries) and designs (e.g., studies based on Electronic Health Record data versus randomized clinical trials), with particular focus in Pediatrics. I also am involved in the development of guidelines for the conduct and reporting of systematic reviews and meta-analyses on child health (PRISMA-PC and C; Preferred Reporting Items for Systematic Reviews and Meta-Analyses). In addition, as a member of the International Steering Committee of StaR Child Health, I am involved in empirical projects for the promotion of evidence-based standards in Pediatric Clinical Research.

Cornelia Dekker, MD

Professor

Current Research and Scholarly Interests The overarching theme of our research activities is human response to natural virus infection and to vaccines. We have conducted several studies of adult, toddler and infant immune response to initial infection with human cytomegalovirus (HCMV). Our largest was a project in which we screened 20,000 newborn infants at Stanford, El Camino and Santa Clara Valley Hospitals for evidence of congenital HCMV infection. Those infants identified as being infected were enrolled into a 3-year prospective study for medical, audiology and immunology screening. The hearing screening portion was designed to identify, as early as possible, infants who develop sensorineural hearing loss as a result of this infection. A second area of clinical research is supported by Dr. Mark Davis' NIH-funded CCHI U19 project entitled "Protective Mechanisms Against Pandemic Respiratory Virus" and the newer HIPC U19 project entitled "Vaccination and Infection: Indicators of Immunological Health and Responsiveness". To provide samples for the lab projects we immunize children and adults (including elderly) with one of four different, licensed influenza vaccines (Fluzone, Fluzone high-dose, Fluzone Intradermal or FluMist) to study in detail the immune response to immunization given by various routes. Blood samples collected from study subjects are analyzed for influenza-specific B and T-cell responses as well as gene expression studies and cytokine analyses. Our latest studies have focused on genetic vs. environmental influences by enrolling fraternal and identical twins. Under the HIPC U19, we are conducting a study of the shingles vaccine in twins and non-twin adults for a close examination of T-cell responses. We also have conducted a study of natural influenza infection for the past 3 years in children and adults to collect NP swabs and blood samples in collaboration with researchers in the Greenberg lab who study how B cells and T cells respond to influenza virus infection. Our group also is funded as part of the Vaccine Treatment and Evaluation Units by NIH through our collaborators at Vanderbilt University. We have conducted studies of avian, novel H1N1 and seasonal influenza vaccines and a new malaria vaccine under this subcontract. A study of a new DNA vaccine against influenza is ongoing under sponsorship by EMMES Corporation and the Vaccine Research Center at NIH. A fourth area of interest has been vaccine safety. Stanford was one of six designated Centers for Immunization Safety Assessment (CISA) sponsored by the CDC for a 10 year period. The network provided consultation to CDC on evaluation and treatment of adverse events following immunization with licensed vaccines, developed protocols to study certain events that occur following immunization (including hypersensitivity reactions, safety of live viral vaccines in immunodeficient children, genetics study of Guillain-Barre syndrome patients). We also collaborate with Dr. Greg Enns on a study of the safety of influenza vaccine and its metabolic effects in patients with the MELAS mtDNA polymorphisms.

Rishi Desai, MD, MPH

Clinical Instructor

Current Research and Scholarly Interests  As a clinician and educator, my primary interest is in optimizing online learning for patients/families and healthcare trainees/workers.

Kara DuBray, MD

Clinical Instructor

My research interests over time have included etiologies and clinical outcomes of pediatric encephalitis and predictors of severe disease.

Elizabeth Egan, MD, PhD

Assistant Professor

Current Research and Scholarly Interests Severe malaria caused by Plasmodium falciparum is a leading cause of morbidity and mortality in the developing world, particularly among young children and pregnant women. In humans, these parasites exclusively infect red blood cells during the clinical stage of illness. Malaria has helped shape the human genome by selecting for certain red blood cell polymorphisms that protect individuals from severe disease. However, the lack of a nucleus in red blood cells has hindered our ability to study genetic interactions between these unusual host cells and P. falciparum parasites. Recently, we developed a hematopoietic stem cell-based approach to tackle this issue, in which we can genetically alter nucleated hematopoietic precursor cells and differentiate them ex-vivo to mature erythrocytes that can be infected by P. falciparum. Using this approach, we performed a forward genetic screen of human blood groups to identify critical host factors for P. falciparum, and discovered several candidates that appear to be required for efficient parasite invasion of red blood cells. We found that the Cromer blood group antigen CD55 (DAF) is essential for parasite invasion and is necessary for proper attachment of merozoites to the erythrocyte surface. The requirement for CD55 appears to be strain-transcendent, suggesting that it may act as a critical receptor during malaria infection. We are currently pursuing fundamental questions related to host-pathogen interactions in malaria, with the host erythrocyte as a focal point. We employ a variety of approaches spanning molecular parasitology, stem cell biology, cell biology, biochemistry and genomics.

Hayley Gans, MD

Clinical Associate Professor

Current Research and Scholarly Interests The focus of my laboratory is defining the immune response to viral vaccines evaluating the ontogeny of responses in infants and limitations in immunocompromised hosts. We have studied the memory effector T cells response in infants given an early two-dose measles vaccine regimen, measuring CD4+, CD4+CD45RO+ and CD4+CD45RO+CCR7-T cells that produce IFNg;. We have also analyzed key markers of activation, using cell surface markers CD69 and CD40-ligand. In addition, we have studied innate immunity and the interactions with the adaptive immune system. We have measured dendritic cell and monocyte populations and function in infants and children and the effects on measles-specific CD4+ T cell responses. These analyses have also been applied to both term and preterm infants receiving polio vaccine, and children receiving varicella vaccination. Our findings have revealed relative limitations in both the innate and adaptive immune system of healthy infants and children as compared with adults. Currently, we are investigating mechanisms responsible for these restrictions. We are also examining the acquisition and persistence of viral immunity in two immunocompromised states, HIV infection and transplantation. The goals of these studies are to define immune profiles in populations where obstacles to vaccination exist to offer insights for the development of novel vaccine strategies. In my role as Co-director of the Pediatric Infectious Diseases Program for Immunocompromised Hosts I am involved with research related to these populations, including outcome studies, epidemiologic studies focusing on respiratory illness in solid organ transplant, fever and neutropenia in Oncology, and risk factors for Post-transplant Lymphoproliferative Disease and cytomegalovirus disease in transplant recipients. In addition, we are studying the efficacy of vaccines and prophylactic measures, such as synagis, in these populations.

Francesca Geertsma, MD

Clinical Associate Professor

Current Research and Scholarly Interests  I have a long standing interest in pediatric coccidioidomycosis and graduate medical education. I also continue to be involved in pediatric HIV medicine.

A. Desiree LaBeaud, MD, MS

Associate Professor

Current Research and Scholarly Interests Arthropod-borne viruses are emerging and re-emerging infections that are spreading throughout the world. Our laboratory investigates the epidemiology of arboviral infections, focusing on the burden of disease and the long-term complications on human health. In particular, Dr. LaBeaud investigates dengue, chikungunya, and Rift Valley fever viruses in Kenya, where outbreaks cause fever, arthritis, retinitis, encephalitis, and hemorrhagic fever. Our main research questions focus on the risk factors for arboviral infections, the development of diagnostic tests that can be administered in the field to quickly determine what kind of arboviral infection a person has, and the genetic and immunologic investigation of why different people respond differently to the same infection. Our long-term goals are to contribute to a deeper understanding of arboviral infections and their long-term health consequences and to optimize control strategies to prevent these emerging infections. Our laboratory also investigates the effects of antenatal and postnatal parasitic infections on vaccine responses, growth, and development of Kenyan children.

Grace M. Lee, MD, MPH

Professor

My work focuses on developing quality metrics for use in pediatrics, evaluating the impact of payment policies on health outcomes, preventing healthcare-associated infections, and conducting near real-time surveillance to monitor the safety of medical product use.

Yvonne Maldonado, MD

Professor

Current Research and Scholarly Interests The research I have conducted has been focused on epidemiologic aspects of viral vaccine development and prevention of perinatal HIV transmission. A major project has been to identify the molecular epidemiology of factors affecting the immunogenicity of oral polio vaccine (OPV) among children living in developing areas of the world, where OPV immunogenicity is poor. We have identified several factors which affect the poor immunogenicity of OPV and will conduct clinical studies to attempt to improve immunogenicity. We are now working on ways to understand the transmission and circulation of polio vaccine derived viruses, which may cause polio, and how to use this information in global eradication of polio. I also work on perinatal HIV infection, including strategies to prevent breastfeeding transmission in developing settings as well as understanding how to maximize prevention strategies among pregnant women in developed countries. A second recent project has been to define the ontogeny of the immune response to measles vaccine among young infants. The purpose is to identify specific humoral and cell-mediated immune responses to measles vaccine which affect vaccine immunogenicity and induce the immunosuppressive effects associated with measles vaccination. A final project I have conducted since 1989 involves a long term natural history study of infants with perinatal HIV exposure and infection. This computer-based study involves following all HIV-exposed and infected infants living in the Northern California and defining factors associated with progression of HIV-related disease.

Roshni Mathew, MD

Clinical Assistant Professor

Current Research and Scholarly Interests  As the Associate Medical Director of Infection Prevention and Control (IPC) at Lucile Packard Children’s Hospital, I work with the IPC nurse specialists to oversee the infection prevention work that happens on a daily basis. This work includes steps toward preventing hospital acquired infections (HAIs) as well as identifying and formulating interventions when we encounter HAIs. I co-chair the Central Line Associated Blood Stream Infections (CLABSI) and Catheter Associated Urinary Tract Infections (CAUTI) Hospital Acquired Conditions committees for the hospital. The nursing and physician leads of all units of the hospital are members of these committees, whose goal is to reduce these hospital acquired conditions to zero. We have developed catheter insertion and maintenance bundles that are standardized across the hospital. The audits and process checks done on a regular basis help us understand barriers and opportunities for improvement and implementation of best practices. In addition, IPC team members develop procedures to prevent and manage exposures, including collaboration with hospital and county disaster groups to plan for infectious disease emergencies. IPC insures safe construction and renovation practices, provides education to all staff regarding infection control practices and explores new innovations that might prove beneficial in further reducing the number of HAIs.

James McCarty, MD

Clinical Professor

Current Research and Scholarly Interests "I have an interest in pediatric coccidioidomycosis and I am participating in several studies, in collaboration with the California Department of Public Health, of the epidemiology and natural history of this disease in children. I am also working with the Infectious Disease division at Valley Children's Hospital in Madera, CA on a study evaluating the inflammatory response, including cytokines and lymphocyte subsets, of children with acute coccidioidomycosis.

Sruti Nadimpalli, MD, MPH

Clinical Assistant Professor

Current Research and Scholarly Interests  My research interests center around the diagnosis of pulmonary infections in immunocompromised children. I have a particular interest in the application of recently-developed, primarily molecular methods to bronchoalveolar lavage specimens in the diagnosis of these infections. Validation and refinement of these high-sensitivity methods carries implications for standardizing and improving the care of immunocompromised children, as well as optimizing infection-prevention and control strategies.

Trung Pham, MD, PhD

Instructor

Current Research and Scholarly Interests Many pathogenic bacteria, such as Mycobacterium tuberculosis and Salmonella enterica, establish chronic latent infections to survive long-term within host tissues and continue community transmission. Chronic infections remain great clinical challenges as many infected individuals are asymptomatic in latent stage, and there is a paucity of effective means to monitor and modulate disease progression, therapy responsiveness, reactivation risk, and disease transmission. We utilize a novel latent murine Salmonella infection model to elucidate functions and mechanisms of innate immune responses during chronic bacterial infections. Our long-term goal is to identify critical molecular and cellular immune factors that can be exploited for diagnostic and therapeutic purposes.

Philip Pizzo, MD

Professor

Current Research and Scholarly Interests My contributions to science have spanned work in pediatric oncology, infectious diseases, immunology and also medical education and health policy. Some themes have included: 1) The Diagnosis, Treatment and Prevention of Infectious Complications in Compromised Hosts: These studies provided the foundation for the management of infection in cancer patients and other compromised hosts and led to reductions in morbidity and mortality in cancer patients, helping to make modern cancer therapy feasible. 2) Pathogenesis and Treatment of HIV and AIDS in Children: This work helped define the pathogenesis of HIV infection in children, focusing particularly on immuno- and neuropathogensis. The work of my group at NCI led many of the early preclinical and clinical trials in pediatric AIDS and enabled four antiretroviral agents to proceed from IND to NDA. 3) Pediatric Oncology: My work has spanned a number of decades of advances in childhood cancer and is partly codified in my textbook Principles and Practice of Pediatric Oncology, the 7th edition of which will be published in late 2015. 4) Health Policy and Healthcare Deliver: I have led a number of policy studies including issues in healthcare reform, medical and graduate medical education as well as important healthcare issues like chronic pain and end-of-life care. 5) Midlife Career Transformation: I am now leading a new program at Stanford, the Distinguished Careers Institute that uses higher education to give individuals in midlife a renewed purpose along with community building and a recalibration of wellness so that they can improve the world.  

Charles Prober, MD

Professor

Current Research and Scholarly Interests My area of research interest is focused on the epidemiology, pathophysiology, prevention, and treatment of infections in children. Much of my research experience has focused on viral infections, especially those caused by herpes simplex virus (HSV). I have conducted a number of studies concerned with the epidemiology of HSV-2 infections in pregnant women, their partners, and neonates. Recently, I have extended these epidemiologic studies to adolescents. I have also conducted studies on the immunologic response to HSV infections, including humoral and cell mediated responses. Furthermore, I have participated in a number of studies evaluating optimal therapy of HSV infections in pregnant women and neonates and HSV vaccine protocols. My interest in antiviral therapy extends beyond HSV infections; I have been involved in a number of studies of therapy for respiratory viral and HIV infections. My interest in bacterial infections includes the evaluation of a number of antibacterial agents (Phase I-III studies). I also am interested in the evaluation and management of infections in compromised hosts including neonates, transplant and chemotherapy recipients. I also am interested in developing interventions to reduce the inappropriate utilization of antimicrobial agents in ambulatory and hospital environments. I am keenly interested in medical education at the undergraduate, medical school, residency, and fellowship level. My educational focus has centered on microbiology and infectious diseases and on the education of clinical research scientists.

Hayden Schwenk, MD, MPH

Clinical Assistant Professor

In the face of rising rates of multidrug resistance, there has been a growing recognition that antimicrobial effectiveness must be regarded as a limited resource. As the Medical Director of the LPCH Antimicrobial Stewardship Program (ASP), I am interested in identifying and implementing strategies that improve antimicrobial utilization at our institution. At present, our program has focused on the role of audit and feedback and how stewardship findings can be reported back to prescribers in a way that is most likely to ensure improvement in antimicrobial prescribing. I have a particular interest in immunocompromised populations and the ways in which evidence-based practice can be used to improve antimicrobial utilization in these patients. I also enjoy quality improvement work and am currently collaborating with perioperative services on efforts to improve surgical site infection rates at our hospital.

Nivedita (Nita) Srinivas, MD

Clinical Assistant Professor

My research interests focus on resident education and the training of future leaders within the field of Quality Improvement. I am currently the site lead for the ICAP (Improving Community Acquired Pneumonia management) quality improvement project through the American Academy of Pediatrics’ Value in Inpatient Pediatrics (VIP) Network. In addition, I have a strong interest in improving the management of other common pediatric infections such as bronchiolitis and urinary tract infections.

David Vu, MD

Instructor

Current Research and Scholarly Interests  My research interests center on molecular determinants of human immunity, in particular, to dengue virus. Dengue virus is estimated to infect up to 390 million people per year, and can cause symptoms ranging from fever, rash and bone and joint pain, to vascular leak leading to hypovolemic shock and death. There is no licensed vaccine, and our understanding of mechanisms of protection against developing dengue infection or disease is incomplete. Better understanding of human immune responses to dengue virus will aid in the development and evaluation of novel vaccines and/or therapeutics.