Associate Members and Their Research Interests
Aijaz Ahmed, MD, Assistant Professor, Gastroenterology & Hepatology
I am a Transplant Hepatologist with full-time clinical responsibilities.
I am interested in natural history and management of HCV (hepatitis C virus) pre- and post transplant.
Martin Angst, MD, Associate Professor, Anesthesia
Research interests: Our human experimental pain research laboratory was launched in 1995. Initial research focused on using experimental pain models in phase I/II clinical trails testing for analgesic efficacy and profile of novel analgesic drug candidates (systemic a2-adrenergic agonists) and of established analgesic drugs delivered with aid of innovative technology (opioids and oral osmotic pump systems). A second early interest examined the mode and site of action after intrathecal or epidural administration of analgesic drugs (spinal versus supraspinal effects).
Today, our laboratory is active in three major research areas. First, with the aid of various pain models mimicking acute pain, inflammatory pain, and pain due to amplified neuronal processing at the level of the spinal cord, we study plastic changes within the central nervous system as a consequence of analgesic drug therapy (opioid induced pain hypersensitivity). Second, we are developing a biomarker assay in humans (cytokines, growth factors, neuropeptides, prostaglandins) for early validation or rejection of novel anti-inflammatory and analgesic drug candidates. Third, we are searching for genetic differences (single nucleotide polymorphisms) responsible for inter-individual variations in pain sensitivity and responsiveness to analgesic drugs. In addition to the experimental pain models, we use techniques such as micro-dialysis, laser-doppler imaging, and immunohistochemistry to find answers to our questions.
Walid Ayoub, MD, Clinical Assistant Professor, Gastroenterology & Hepatology
My research interests include management of chronic viral hepatitis B and C, management of hepatic encephalopathy, autoimmune hepatitis, overlap syndrome, liver transplantation and recurrent hepatitis C post liver transplantation.
Michael Bachmann, MD, D.Sc., Research Associate, Pediatrics
Advances in transplantation and in emerging stem cell and regenerative medicine therapies will require the generation of long-lived tolerance with few, if any adverse effects. We have therefore developed an in vivo molecular genetic screen to isolate and identify genes and gene combinations that can extend transplant survival in genetically mismatched mice. Our ultimate goal is to develop these genes and gene combinations further into therapeutic reagents that can secure the survival of transplanted cells, tissues and organs without the need for prolonged drug-mediated immunosuppression.
Research interests: transplantation, immunology, molecular imaging, virology (HIV/AIDS)
Niaz Banaei, MD, Instructor, Pathology, Associate Director, Clinical Microbiology
My research interests include development and implementation of rapid diagnostic assays for the detection, identification, and susceptibility testing of clinically important mycobacteria. Furthermore, I am interested in understanding the role of M. tuberculosis lipoproteins and lipoprotein processing in the pathogenesis of tuberculosis.
Jonathan S. Berek, MD, MMS, Professor and Chair, Obstetrics and Gynecology
Dr. Berek is a Professor and Chair of the Department of Obstetrics and Gynecology at the Stanford University School of Medicine, and is Chief of Obstetrics and Gynecology at the Stanford University Hospital and Clinics. He is a gynecologic oncologist at the Stanford Cancer Center, and helps to direct clinical/translational research in gynecologic cancers. Dr. Berek’s primary research interest is in the immunology and immunotherapy of ovarian cancer, and the development of experimental models and clinical trials. His research team's initial work with the use of intraperitoneal immunotherapy developed the basis for regional biologic therapy in ovarian cancer. Through collaborative work, his team is focusing on the development of vaccines, monoclonal antibodies and other novel biological therapeutics for ovarian cancer. Dr. Berek was a Principal Investigator for the Gynecologic Oncology Group for two decades. He has a grant from the Ovarian Cancer Research Fund that funds his role as the Group Chair and Principal Investigator of the Cooperative Ovarian Cancer Group for Immunotherapy (COGI). He is the Principal Investigator of a National Institute of Health (NIH) Grant, Women’s Reproductive Health Research (WRHR), and Principal Investigator of the NIH Grant, Bridging Interdisciplinary Research Careers in Women’s Health (BIRCWH).
Ellen Jo Baron, PhD, Professor, Pathology
Rapid diagnostic testing for infectious diseases, training basic microbiology skills in developing world.
Helen Blau, PhD, Professor, Microbiology & Immunology, Pharmacology and of Chemical and Systems Biology
Dr. Helen M. Blau is the Donald E. and Delia B. Baxter Professor and Director of the 60-person Baxter Laboratory at Stanford University School of Medicine. Dr. Blau has made substantial contributions to the understanding of cell differentiation during development by showing that the differentiated state, contrary to dogma, is plastic and can be changed. These findings are important in understanding how the differentiation process goes awry in muscular dystrophy and in cancer. By deconstructing and reconstructing the niche in bioengineered niches, her laboratory is investigating the extrinsic signals that control cell fate an how these can be exploited to induce change. By fusing cells in stable heterokaryons, her laboratory is elucidating the cell intrinsic molecular mechanisms that are required to impart changes to cells destined for different functions. These findings are of great fundamental importance and critical to all stem cell research.
Clark Bonham, MD, Associate Professor, Surgery, Multi-Organ Transplantation
Transplant immunology
Wes Brown, MD, Associate Professor, Bone and Marrow Transplantation
Stephan Busque, MD, Associate Professor, Surgery, Multi-Organ Transplantation
Pre-clinical and immunosuppression, islet cell transplantation, organ preservation.
Eugene Butcher, MD, Professor, Pathology
We study the trafficking of white blood cells (lymphocytes, dendritic cells, monocytes, etc.), including their interactions with the endothelial lining of blood vessels at sites of leukocyte extravasation, and their chemotactic responses in tissues. These events regulate immune responses by controlling the access of leukocytes to sites of inflammatory or immune reaction in the body. We discovered that lymphocytes use a variety of different adhesion molecules or "homing receptors" to recognize organ (and/or inflammation)-specific vascular ligands or "addressins" that define the tissue position (address) of blood vessels in the body. Our studies have shown that these adhesion receptors act coordinately with G protein-linked serpentine chemoattractant receptors in a multi-step process that controls the specificity and provides combinatorial diversity in leukocyte trafficking.
A major focus of the group is on understanding the physiologic significance and control of targeted lymphocyte trafficking. To this end, we are studying the specialized homing mechanisms and functional properties of tissue infiltrating lymphocytes involved in local immune, autoimmune and regulatory responses in the GI tract (intestines, liver), skin, lungs, and other sites. Genetic, antibody and small molecule-based approaches allow us to define the role of trafficking molecules and mechanisms in models of autoimmune and infectious diseases. We are also exploring mechanisms that imprint lymphocyte homing and chemokine receptor expression during tissue-specific immune responses, and are developing techniques to recapitulate such regulation in vitro for cell targeting and therapy. Dendritic cells (DC) play an important role in this context, and we are interested in the mechanisms by which specialized DC "interpret" and process local environmental signals (e.g. vitamins, metabolites, cytokines) to control T cell trafficking and regulatory vs. effector activities. Finally, we have shown that leukocytes can effectively navigate through complex chemoattractant arrays, and we are exploring the mechanisms that permit this surprising behavior through computer simulations of chemotactic behavior, and through experimental manipulation of the molecules and receptors involved.
Atul Butte, MD, PhD, Assistant Professor, Center for Pediatric Bioinformatics
The long-term research goal of the Butte Lab is to develop bioinformatics
methods in integrative biology, or reasoning over the many available
genome-scale measurement and experimental modalities, and apply these
methods to study complex disorders in genomic medicine, especially obesity
and type 2 diabetes mellitus. The Butte Lab has three main directions in
exploring integrative biology. First, we have developed bioinformatics
methods to integrate genomic, genetic, phenotypic, clinical, and
gene-knockout data from multiple sources and phenotypes and reason over
these data. An example of this was our recent work in adipogenesis
published in Nature Cell Biology (2005). Second, we have developed tools to
automatically index and find genomic and proteomic data sets based on the
phenotypic and contextual details of each experiment. We used these tools
to create a comprehensive phenome-genome network published in Nature
Biotechnology (2006). Third, we have been funded by NIGMS and HHMI to build
a novel gene-expression-based classification scheme for diseases across the
entire field of medicine.
Alexander Butwick, MD, Instructor, Anesthesia
Obstretic anesthesia. Hemostasis and coagulation in pregnant patients in the peripartum and postpartum periods.
Brendan Carvalho, MD, Assistant Professor, Anesthesia
The role of inflammatory mediators in surgical wounds and pain. In particular I have been looking at cesarean wounds and the role of cytokines, NGF, PGE2 and pain/analgesic use post-operatively.
Ricardo Castillo, MD, Associate Professor, Pediatrics -- Gastroenterology
Study of the interaction and role of nutrients and intestinal growth factors in enhancing intestinal adaptation and allograft viability using animal models for short bowel syndrome and orthtopic intestinal transplantation.
Study of immunosuppression regimens and induction of immune tolerance in intestinal transplantation.
Eliza Chakravarty, MD, Assistant Professor, Immunology & Rheumatology
We study novel immune modulating therapies for the treatment of systemic autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. By utilizing validated outcome measures to monitor changes in clinical diseases patterns before and after therapy, we hope to better understand short- and long-term safety and efficacy of newer treatment options.
Chang-Zheng Chen, PhD, Assistant Professor, Microbiology & Immunology
We study the genetic networks controlled by regulatory RNAs, such as
microRNAs and small interfering RNAs, and the roles of these RNAs in
modulating the development, function and pathogenesis of vertebrate
immune systems. Animal genomes not only contain the genetic information to make
messenger RNAs (mRNA), which are then translated into proteins, but
they also carry the genetic information to make non-coding RNAs
(ncRNAs), which play important roles in regulating gene expression
and animal development. Among all the ncRNA species, microRNAs
(miRNAs) are small ncRNAs of ~22 nucleotides in length that form
sequence-guided interactions with the cognate mRNA target genes and
regulate gene expression at the posttranscriptional level. We have
shown that miRNAs may be integral components of the molecular
circuitry controlling normal hematopoiesis and leukemogenesis. miRNAs
are abundantly present in various immune cell populations. Many are
differentially regulated during the development of immune cells. More
importantly, some lineage-specific miRNAs can modulate the
differentiation of hematopoietic stem/progenitor cells. Nevertheless,
as a newfound layer of genetic regulation, the mechanisms through
which miRNAs and other ncRNAs regulate gene expression, as well as
their biological functions in vertebrate development, are yet to be
unraveled. The research in my laboratory focuses on the roles of
miRNA- and other ncRNA-mediated gene regulatory networks in
modulating the development, function, and pathogenesis of vertebrate
immune systems.
George Chen, MD, Postdoctoral Medical Fellow, Medicine
Chronic graft versus host disease, tumor antigens
Clifford Chin, MD, Associate Professor, Pediatrics - Cardiology
Pediatric Heart Transplant: development of non-invasive evaluations for the determination of allograft rejection and coronary artery disease; post-transplant hyperlipidemia; prevention of graft coronary artery disease and
Pediatric Exercise Testing: development of new techniques
Lawrence Chu, MD, Assistant Professor, Anesthesia
Immunomodulation related to opioid exposure and opioid withdrawal. Pain research study.
David Clark, MD, Associate Professor, Anesthesia
My laboratory's interests are in the participation of cytokines and other inflammatory mediators in acute and chronic pain conditions. The laboratory has rodent models of neuropathic, fracture, incisional and other types of pain. We attempt to identify cell types producing the mediators, the mechanisms controlling the production of the mediators and the target cells for these substances in producing pain. We work closely with collaborators translating the rodent observations into human studies.
Karl V. Clemons, PhD, Infectious Diseases and Geographic Medicine
Our group (David A. Stevens is the PI) has interests in innate and acquired
immune response to mycoses in normal and immunocompromised hosts. We
examine host-cell killing mechanisms, global cytokine response and
regulation, and immunomodulation of the host-response. We are particularly
interested in the immune response to fungal infection in the CNS and the
genesis of vasculitis associated with some CNS infections. We are involved
in both the laboratory and clinical arenas with respect to diagnosis, and
therapy of mycoses.
Waldo Conception, MD, Associate Professor, Surgery -- Multi-Organ Transplantation
My research interests include clinical outcomes in pediatric kidney
transplantation, long term outcomes in pediatric kidney transplantation,
and immunosuppression."
Carol K. Conrad, MD, Assistant Professor, Pediatrics,
Pediatric Pulmonary Medicine
My research interests are translational/clinical. I am currently involved in a Phase IIB multicenter study of the effects of N-acetylcysteine in Cystic Fibrosis patients. This study is concentrating on the effects of NAC as an anti-inflammatory, and in collaboration with the Herzenberg Lab, we are looking to determine it's effects of redox and inflammatory pathways. I also am involved in pediatric lung and heart-lung transplantation. I collaborate with other pediatric lung transplant centers internationally. We will soon begin a study in children who have received lung transplants that evaluates mechanisms of viral infection that trigger allograft rejection.
Marc Coram, PhD, Assistant Professor, Health Research & Policy - Biostatistics
Interested in novel biostatistical challenges that arise in the analysis of immune related experiments.
Ken Cox, MD, Senior Associate Dean for Pediatric and Obstetric Clinical Affairs and Professor, Pediatrics - Gastroenterology
My research interests include the study of infectious and immunologic causes
of pediatric liver diseases, primary sclerosing cholangitis and biliary atresia,
and the pre- and post-operative management of pediatric liver transplant recipients to
improving outcome by improvements in pre-operative care and timing of
transplant and by using new immunosuppressive therapies to reduce rejection and infections.
Amarendra Das, MD, PhD, Assistant Professor, Stanford Medical Informatics, Psychiatry & Behavioral Science
Research in Amar Das's laboratory focuses on the advancement of software tools to support temporal reasoning, data integration, and collaborative systems in healthcare and the life sciences. We are currently applying our methods to translational research, in which the value of high-throughput technologies depends on adequately capturing the clinical context within which gene and protein expression data are collected. In collaboration with the Immune Tolerance Network -- a NIH funded scientific collaboration among researchers studying immune tolerance mechanisms through clinical studies -- we are creating computational tools to undertake large-scale, automated integration of mechanistic and clinical data. Our software approach relies upon the use of ontologies to model patient information, clinical protocols, mechanistic studies, and biological pathways within a knowledge-based framework based on the emerging standards to the Semantic Web.
Tami Daugherty, MD, Clinical Assistant Professor, Gastroenterology and Hepatology
I am a transplant Hepatologist with full-time clinical responsibilities.
I am particularly interested in the natural course and management of
recurrent Hepatitis C after liver transplant, and the effect of
immunosuppression on HCV recurrence.
Cornelia L. Dekker, MD, Associate Professor of Pediatrics, Medical Director, Stanford-LPCH Vaccine Program, Division of Pediatric Infectious Diseases
The Stanford-LPCH Program provides an infrastructure for conducting clinical studies of new vaccines in children and adults. Current emphasis is on testing of new seasonal influenza, avian influenza, malaria and smallpox vaccine candidates. We also are completing a 20,000 newborn infant screening project for congenital HCMV infection, with prospective clinical, audiology and immunology follow-up. Other research interests include vaccine safety, immune responses to HCMV infections and antiviral therapy.
Tony De Tomaso, PhD, Assistant Professor, Biological Sciences and Pathology
We are studying a natural transplantation reaction in a primitive chordate organism, /Botryllus schlosseri/. Allorecognition is controlled by a single, highly polymorphic locus called the fuhc, with both the ligand and putative receptor family encoded within a 250 Kb genomic region. Functionally, this system appears to work in a fashion analogous to the missing-self recognition of vertebrate natural killer cells. Our current focus is on understanding the molecular mechanisms underlying this highly discriminatory, yet innate recognition system as well as the processes responsible for the development of self-tolerance.
Firdaus Dhabhar, PhD, Associate Professor, Psychiatry and Behavioral Sciences
research_interests: Although the term "stress" generally has a "bad" reputation, a physiological stress is response is nature's fundamental survival system. For example, without a fight or flight response, a predator has no chance of catching its prey just as the prey has no chance of escape. My laboratory studies how stress-induced physiological changes impact immune function. We are engaged in identifying biological mechanisms that mediate (and differentiate) the recently appreciated immunoenhancing effects of short-term stress from the well-known immunosuppressive effects of long-term stress. We examine stress effects on leukocyte trafficking, innate/adaptive immunity, and cytokine gene/protein expression using human and murine models of skin immunity, surgery, and cancer. Our long-term goal is to develop behavioral and/or pharmacologic interventions designed to harness a patient's psychophysiology to selectively enhance (during vaccination, surgery, infection, or cancer) or suppress (during inflammatory and autoimmune disease) an immune response depending on the clinical needs of the patient.
Walderez Dutra, PhD, Visiting Professor, Institute for the Biological Sciences, Brazil
Over the past ten years my laboratory has been studying the cellular and
molecular mechanisms behind differential evolution of human Chagas disease
and leishmaniasis, two tropical parasitic diseases induced by intracellular
protozoans. We evaluate T-cell effector and regulatory functions,
parasite-host cell interactions and host genetic factors in groups of
individuals with well-defined clinical forms of Chagas' disease and
leishmaniasis, looking for markers of disease progression or susceptibility.
More recently, we have also expanded our studies to look at cellular and
genetic factors behind human periodontal disease in collaboration with a
team of clinical dental health professionals in Brazil. Thus, our studies
are focused towards the understanding of the mechanisms of establishment of
protective versus pathogenic responses in human diseases."
Edgar Engleman, MD, Professor, Pathology
The goal of this laboratory is to better understand dendritic cell biology with the objective of using this information to discover and develop more effective immunotherapeutic approaches to disease. We pursue this goal by performing experiments in both mice and humans. In our initial clinical studies antigen pulsed dendritic cells were administered to patients with cancer or life-threatening viral infections in order to induce specific immunity. The results of these trials have been extremely encouraging. More recently we have focused our studies on the development and life cycle of dendritic cells, including Langerhans cells, and the results have not only shed new light on dendritic cell biology but also have led to our ability to target dendritic cells in vivo without having to manipulate these cells in vitro. We believe that this new approach will eventually make it possible to downregulate as well as upregulate the immune system in an antigen specific manner.
C. Garrison Fathman, MD, Professor, Chief of the Division of Immunology & Rheumatology
His substantial scientific contributions in the areas of cellular and molecular immunology and immunogenetics have brought him international recognition. As Director of the CCIS, Dr. Fathman has initiated a multidisciplinary approach to study and treat immune based diseases, and has initiated several new approaches to education and community outreach. His lab's research includes studying T cell anergy at a molecular level, pathogenesis of NOD T1D analyzed by genomic and proteomic technologies, and targeted therapies for animal models of autoimmune diseases including mechanism of action studies.
Daniel S. Fisher, PhD, Professor, Applied Physics and, by courtesy, Biological Sciences
Dr. Fisher is a theoretical physicist interested in microbial evolution and cell biology and is collaborating on dynamics of zebra fish immune system.
Magali Fontaine, MD, Assistant Professor, Pathology
Dr. Fontaine's research interests focus on both blood transfusion and
cellular therapy. Her focus on transfusion is primarily clinically
oriented. As the Associate Director of the Transfusion Service at Stanford
Medical Centers, she promotes and oversees the safe practice of blood
transfusion. Her work in the field of cellular is focused on helping to
address the national shortages of blood and organs for transfusion and
transplantation. One of the main projects undertaken in the Fontaine's lab
is to improve islet cell isolation for transplantation to treat type 1
diabetes and find new strategies to protect islets during the isolation
procedure and post-transplantation.
Curtis Frank, PhD,
Professor; W.M. Keck, Sr. Professor in Engineering
Frank explores the molecular structure of high polymers and small amphiphilic molecules capable of self-organization through photostationary and transient fluorescence, Fourier transform infrared spectroscopy, surface plasmon spectroscopy, and optical and atomic force microscopy. He studies polymers, fatty acids, polypeptides, surface coupling agents, dendrimers, and liquid crystals at the air/water interface and in constrained geometries on solid substrates, organic/inorganic nanocomposites, and applications of polymers in microelectronics and magnetic recording.
Stephen Galli, Professor Pathology, Microbiology & Immunology
The goals of Dr. Galli's laboratory are to understand the regulation of mast cell and basophil development and the expression of mast cell and basophil function, and to develop and use genetic approaches to elucidate the roles of these cells in health and disease.
Hayley Gans, MD, Assistant Professor, Pediatrics -- Infectious Diseases
My main research focus has been on the immune responses of infants to viral vaccines, defining mechanisms responsible for the relative immunodeficiency described in infants compared with older children and adults. We have compared the immune responses in 6, 9, and 12 month-old infants who were given a primary dose of measles or mumps vaccination, utilizing lymphoproliferation, cytokine production and flow cytometry. Our immune investigation has been on memory T cell responses, antigen presentation and quality of the humoral responses. We are also evaluating immunity after primary varicella vaccine administered at 12 versus18 months of age, and after one compared with 2 doses in childhood. Another area of interest has been on alternative regimens and routes of administration of the measles vaccine. We have evaluated early and persistent immune responses to an early 2 dose measles immunization schedule, given as a first dose at 6 or 9 months followed by a second dose administered at 12 months, with comparisons to infants receiving routine MMR at 12 months. In addition we have collaborated on a comparison of primary measles vaccination administered to 12 and 9 month old infants by aerosol or subcutaneous routes. Additionally, I am Co-investigator on a study evaluating patients with DiGeorge Syndrome. The purpose of this study is to define potential mechanisms that may link reduced thymic output of T-lineage cells with autoimmune disease in patients with chromosome 22q11.2 deletion syndromes.
Mark Genovese, MD, Associate Professor, Associate Chief, Division of Immunology & Rheumatology
He received his bachelor's degree from the University of Notre Dame and his medical degree from the Johns Hopkins University School of Medicine. He completed an internship, residency, and chief residency in the Department of Medicine at Stanford University. He remained at Stanford as a postdoctoral fellow in the Division of Immunology and Rheumatology and subsequently joined the faculty in the same division. Dr. Genovese has established a clinical research program that is focused on bench-to-bedside translational medicine in autoimmune diseases. He has participated in a number of investigator-driven studies and in many multicenter trials. In addition, he collaborates with several other investigators on studies of biomarkers, chemokines, cytokines, and cell surface markers associated with disease progression and response to therapy. Dr. Genovese is also the Director of the Center for Clinical Investigation in the Stanford Department of Medicine. Since joining the faculty at Stanford, Dr. Genovese has served as an editor for the textbook Primary Care Rheumatology and as an associate editor for Kelley's Essentials of Internal Medicine. He is also an editor on the 7th edition of Kelley's Textbook of Rheumatology. Dr. Genovese is an ad hoc reviewer for numerous medical journals, a board member of the Stanford General Clinical Research Center, and he was the recipient of a Center of Immunology at Stanford clinical scholars' award.
Rona G. Giffard, PhD, MD, Professor and Vice-chair for Research, Anesthesia
The focus of research in the Giffard lab is on ischemic brain injury and stroke. Astrocyte response, as well as astrocyte interaction with other brain cells in the setting of injury is one important theme. We are interested in the ability of chaperones to reduce injury, including potential anti-inflammatory effects of Hsp70, and mitochondrial function and ROS generation- including their role in inflammatory response.
Jeffrey Glenn, MD, PhD, Assistant Professor, Gastroenterology & Hepatology
My research interests lie 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, and new biodefense antiviral strategies. As director of the Center for Hepatitis and Liver Tissue Engineering, I also seek to facilitate the conduct of innovative phase I/II trials of novel therapeutics for viral hepatitis, and the integration of those trials with collaborations involving the exciting array of cutting-edge science being performed at Stanford.
Kenneth Gollop, PhD, Associate Visiting Professor, Biochemistry-Immunology
Our laboratory focuses on studying the formation of pathogenic and
protective immune responses in human parasitic diseases, especially
leishmaniasis. Our work over the years has defined specific T lymphocyte
subpopulations producing immunoregulatory cytokines, and in particular we
have recently identified CD4-CD8- T cells with disparate immunoregultory
capacities based on the expression of the alpha/beta vs. gamma/delta TCR.
Moreover, we are studying the early interactions between Leishmania and the
host macrophage to define the early events following infection that could
control the development of the subsequent immune response. The eventual aim
of our studies is to aid in the development of immunomodulatory treatments
and vaccines for the ~20 million people infected with Leishmania worldwide.
Harry Greenberg, MD, Professor, Gastroenterology & Hepatology, Microbiology & Immunology
Dr. Greenberg's current interests are in pathogenic viruses that infect the GI tract, liver and respiratory tract. His primary focus is on molecular mechanisms of pathogenesis, viral determinants of protective immunity, the molecular basis of host range, virulence and tissue tropism, vaccine development, viral immunology, and epidemiology with specific emphasis on the role of enteric viruses in less developed countries.
Paul Grimm, MD, Professor, Pediatrics
Chronic rejection, fibrosis in native and transplant chronic renal disease. Computerized image analysis of biopsy tissue.
David Hirschberg, PhD, Director, Human Immune Monitoring Center
Dr. Hirschberg is involved in the inception and development of the Human Immune Monitoring Center within the Stanford University Medical School. This state-of-the-art facility will bring outside researchers and companies together with Stanford Researchers to accelerate the pace of transferring new technologies to the clinic. Dr. Hirschberg was a Senior Research Scientist at Agilent Technologies where he responsible for the creation of new applications using Agilent's genomic and proteomic platforms. He interacted with thought-leaders in academia and industry, developing new strategies and proof-of-concept experiments that led to peer-reviewed publications. Dr. Hirschberg's developed better ways to measure biomarkers on genomic, proteomic and metabolomic levels, and used Agilent's product line to be more applicable to clinical research and diagnostics. He was involved in the design and validation of Agilent's DNA microarrays, as well as of several prototypes of protein arrays. He has brought several of the projects that he has been involved with to the Immune Monitoring Center at Stanford
Ralph Horwitz, MD, Chair & Arthur L. Bloomfield Professor of Medicine
Clinical Epidemiology; methods for design and analysis of clinical research
Hakuta Hikatura, MD, Instructor, Cardiovascular Medicine
Neeraja Kambham, MD, Assistant Professor, Pathology
Kidney and liver transplantation biopsy studies. Also interested in antibody mediated rejection and protocol kidney biopsies studies.
Mark A. Kay, MD, PhD, Dennis Farrey Family Professor in Pediatrics, and Professor of Genetics
The goals of the Program in Human Gene Therapy are to establish the scientific principles and develop the technologies needed for achieving persistent and therapeutic levels of gene expression in vivo. While our ultimate aim is to use gene transfer to treat human disease, we plan to address basic biological questions that will be important for rational design of vectors for gene therapy applications. Towards this goal, we are working on developing new non-viral and viral vectors for gene transfer and establishing the cellular and molecular mechanisms involved in gene transduction in animals.
Our vector development includes: new episomal DNA vectors, DNA transposons, viral gene deleted adenoviruses, and adeno-associated virus. Hemophilia, human hepatitis virus infection, and diabetes are the three clinical disorders which we have concentrated our efforts but the results obtained will be useful for treating a wide variety of diseases. In the case of hemophilia, we have used our preclinical studies to help support clinical trials using recombinant AAV vectors to deliver a normal copy of the factor IX gene into factor IX deficient individuals. We are currently conducting a Phase I/II trial -"Liver-directed AAV-hFIX administration into severe hemophilia B patients". Recently, we have developed RNAi approaches for treating human Hepatitis B and C infection in animal models, and are pursuing this approach for developing a therapy suitable for humans.
Emmet B. Keeffe, MD, Professor, Chief of Hepatology and Co-Director of the Liver Transplant Program.
His research interests have bridged general and transplant hepatology. He has focused on antiviral therapy of chronic hepatitis B and C and participated in numerous clinical trial evaluating the safety and efficacy of novel agents for these infections. He has helped establish treatment guidelines for the management of chronic hepatitis B. Dr. Keeffe has also published key papers identifying the increased risk of acute hepatitis A or B in patients with underlying chronic liver disease and conducted trials demonstrating the safety and efficacy of hepatitis vaccines in this population of patients. Finally, he is widely published on liver transplant selection criteria and outcomes. He has published more than 500 papers, book chapters and miscellaneous publications.
Karla Kirkegaard, PhD, Chair, Microbiology & Immunology
For many subcellular viruses and parasites, RNA, not DNA, is the carrier of genetic information. This has several interesting consequences for the genetics and biology of the virus. Poliovirus serves as a model to increase our understanding of positive-strand RNA viruses for which no vaccine is available and which remain a significant health hazard: examples include other picornaviruses, such as rhinoviruses, coxsackieviruses and the deadly enterovirus 71 as well as more distantly related positive-strand RNA viruses such as hepatitis C and Dengue fever.
Susan J. Knox, MD, PhD, Associate Professor, Radiation Oncology
Effects of radiation on subsets of immune cells involved in innate and acquired immunity; use of radiation as a component of vaccine strategies; modulation of the immune response by radiation; targeted cancer therapies; redox modulation of apoptotic potential; novel radiosensitizers.
Andreas M. Kogelnik, MD, PhD
My area of research is in translational bioinformatics and systems biology particularly in the area of clinical infectious diseases. I am using large-scale analysis of clinical and genomic data to analyze and identify human host-response signatures to infection with Drs. Stanley Falkow and Ellen Jo Baron. Also with Dr. Baron, I am involved in quality improvement/evaluation efforts in particular examining antibiotic usage through informatics-based analysis on a local and regional level. With Dr. Atul Butte I am integrating genomic data with clinical data to elucidate previously unknown relationship with respect to biomarkers of disease and potential novel treatment options. With Dr. Jose Montoya, I am exploring the paradigm of chronic viral disease and treatment with respect to chronic fatigue syndrome
Sheri Krams, PhD, Associate Professor, Surgery, Multi-Organ Transplantation
My research focuses on understand the role of natural killer (NK) cells in immune events post-transplantation and specifically how we can translate these discoveries to novel therapeutics to induce tolerance to organ allografts. We have also cloned and characterized a novel activation receptor on rodent NK cells and are currently focusing on identifying the natural ligand. Another area of research is the development of strategies to modulate apoptosis, with the goal of decreasing the incidence of primary non-function in solid organ and cellular allografts.
Eswar Krishnan, MD, Assistant Professor, Immunology & Rheumatology
Dr. Krishnan's interests are in clinical epidemiology of rheumatic diseases, clinical and epidemiological databases, and phenotyping SLE.
Richard Lafayette, MD, Associate Professor, Nephrology
Initiating a glomerulonephritis cohort study, including immunologic characterization. Interventional studies of preeclampsia exploring the nitric oxide, endothelin system and effects on glomerular function and morphometry. Outcome studies in dialysis and acute renal failure patients. Interventional and observational studies of glomerular disease, particularly IgA nephropathy.
Peter P. Lee, MD, Associate Professor of Medicine-Hematology
Dr. Lee's research focuses on the mechanistic and translational aspects of the immune response to cancer. In addition to technologies such as dendritic cell and T cell cloning, multi-color FACS analysis and sorting, peptide/MHC tetramers, and DNA microarrays, Dr. Lee's team is developing and utilizing mathematical models and simulation with supercomputers to gain insights into the dynamics (systems biology) of these responses.
Over the past three years, his research has focused on the immune response in breast cancer patients. His published findings last fall (attached) showed that a novel method of using immune cells to predict the outcome of breast cancer could be more accurate than the current method of looking at cancer cells alone. This has led to a major effort in image analysis in cancer. Dr. Lee's team has developed novel image analysis algorithms and software to delineate the type and location of every cell within an entire histological section. This then enables complex analysis of density, architecture, and geometrical relationships between immune cells and cancer cells within tumors and tumor-draining lymph nodes. As such, this line of investigation will provide vastly more information than previously possible from standard histological analysis, and will have important benefits both to the research and clinical arenas.
Ronald Levy, MD, Robert K. and Helen K. Summy Professor in the School of Medicine
Our research concentrates on the study of malignant lymphoma and tumors of the immune system using the tools of immunology and molecular biology to develop a better understanding of the initiation and progression of the malignant process. Receptor molecules present on the surface of tumor cells transmit signals for regulation of cell growth. These receptors include the immunoglobulin molecule on B cell tumors and the T cell receptor on T cell tumors. Questions the lab is currently addressing include:
1. Can a clue to the pathogenesis of lymphoma be derived from a study of their antigen receptors?
2. Can new treatments for lymphoma be developed by targeting receptors with monoclonal antibodies?
3. Can vaccines be developed which can induce an immune response in the host against the receptors on their own tumor?
Shoshana Levy, PhD, Professor, Oncology
Infection by hepatitis C virus (HCV) is associated with B cell
lymphoproliferative diseases. Our studies are aimed at determining whether
these diseases are caused by an immune response that has gone awry. We
hypothesize that HCV subverts the function of its cellular receptor, CD81, a
tetraspanin, which is a costimulatory molecule in B lymphocytes.
David Lewis, MD, Professor, Pediatrics - Immunology
Major interests are in developmental differences between infants and young children versus adults in T-cell immune responses to pathogens and vaccines and in intrathymic development using both human blood samples and murine models; identifying mechanisms for decreased immunity in humans with primary immunodeficiencies.
Rich Lewis, PhD, Professor, Molecular & Cellular Physiology
Our research is focused on the molecular mechanisms of calcium signaling in T cells. One major effort is to understand the function of calcium signals during T cell development. To this end, we have pioneered the application of 2-photon microscopy to visualize thymocyte migration, cell-cell contacts, and calcium signals as cells undergo positive and negative selection in thymic tissue. A long-term goal of this project is to understand how the dynamic signature of Ca2+ signals may help determine cell fate during development. A second major project is to understand how the T cell receptor controls Ca2+ release-activated Ca2+ (CRAC) channels, a class of store-operated channel that generates the sustained Ca2+ signals necessary for T cell activation. We are applying a combination of microscopy (TIRF, confocal and electron), electrophysiology, and molecular biology tools to determine how Ca2+ store depletion causes the ER Ca2+ sensor and the CRAC channel to accumulate at junctions between the ER and the plasma membrane, and how they interact to trigger channel opening.
Bonnie Maldonado, Associate Professor, Pediatrics, Infectious Diseases
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.
Olivia Martinez, Professor, Surgery, Multi-Organ Transplantation
The two major areas of focus in the Martinez lab are: 1) viral and immune mechanisms that govern the autonomous growth of Epstein Barr virus B cell lymphomas 2) T cell regulation of alloimmune responses.
A.C. Matin, PhD, Professor, Microbiology & Immunology
Dr. Matin is interested in evolved enzymes and new prodrugs for cancer chemotherapy; non-invasive bioimaging of drug penetration in solid tumors; molecular basis of antibiotic resistance in bacteria and their biofilms; improved bioremediation by engineered bacteria.
Marc Melcher, MD, PhD, Assistant Professor, Surgery, Multi-Organ Transplantation
I am interested in increasing the benefits of transplant to a greater number of people and studying ways to improve the outcomes of those that receive a transplant. For example we are studying whether gastric bypass surgery on morbidly obese patients with end-stage kidney disease can help them lose enough weight so that they can be safely offered a kidney transplant. In liver transplant patients, I am interested in how the choice of immunosuppressants after liver transplant influences the rate and severity of recurrent
hepatitis C.
Elizabeth Mellins, MD, Associate Professor, Pediatrics-Immunology & Transplant Biology
Our lab focuses on the study of antigen presentation by major histocompatibility complex (MHC) class II molecules. We have been particularly interested in the molecular mechanisms and intracellular steps involved in the generation of complexes between MHC class II molecules and peptides. Our work in this area has elucidated the roles of invariant chain and HLA-DM,
two molecules which regulate peptide-loading of class II molecules. In addition, we have investigated the molecular basis of HLA-DR4 association with rheumatoid arthritis. Ongoing studies deal with:
1. Analysis of the biosynthesis, structure, and structure/function relationships of the HLA-DM and HLA-DO molecules.
2. Regulation of class II biosynthesis in professional antigen presenting cells.
3. Mechanistic basis of HLA allele association with autoimmune disease
4.Pathogen evasion of the class II pathway.
Sara Michie, PhD, Associate Professor, Pathology
Our laboratory studies the molecular mechanisms that control the migration
of lymphocytes into sites of autoimmune-mediated tissue damage, such as
salivary glands in Sjogren's syndrome and pancreatic islets in type 1
diabetes. Our long-term goals include better understanding of the
pathogenesis of autoimmune diseases, and development of novel diagnostic
and therapeutic strategies.
David Miklos, MD, PhD, Assistant Professor, Medicine - BMT
As a Blood and Bone Marrow Clinician and scientist, my research investigates humoral immune reconstitution following allogeneic hematopoietic cell and solid organ transplantation. Our lab has demonstrated allogeneic antibody responses develop against minor histocompatibility antigens in association with chronic graft-v-host disease (GVHD) following allogeneic HCT, and during acute rejection of kidney allografts. In HCT, we have ongoing prophylactic and therapeutic rituximab trials providing patient samples to characterize important B cell, plasma cell, and antibody changes in relation to both beneficial alloimmune responses (GVL), and detrimental (GVHD). In order to discover clinically important new allogeneic antibody targets, we developed serologic screens using both commercial and custom-made high-density protein microarrays. Finally, we have extended our protein microarray expertise to synthesize a microbial protein array allowing human pathogen exposure histories to be in relation to subsequent disease development including cancer, neurologic disorders, and autoimmunity.
Denise Monack, Senior Research Associate, Microbiology and Immunology
Molecular mechanisms of inflammation, specifically activation of
caspase-1/Inflammasome by bacterial pathogens and host-derived signals.
Study persistent Salmonella infections in the gastrointestinal tract and
lymphatics. Study how Francisella modulates the innate immune system.
Jose Gilberto Montoya, MD, Associate Professor, Infectious Diseases
Current interests: toxoplasmosis, immunocompromised host, antibiotics.
Currently I'm working on the impact of serological testing for toxoplasmosis in a reference laboratory (Toxoplasmosis Serology Laboratory at the Palo Alto Medical Foundation Research Institute) in the rates of abortion in women with IgM antibodies.
Richard Moss, MD, Professor, Pediatrics -- Pulmonary Medicine
I am interested in the immunopathogenesis of chronic airways diseases of
childhood. My work includes basic and clinical research. In the area of
basic research, my laboratory has focused on immunoregulation of
inflammation in cystic fibrosis, finding deficiencies of activated T cells
from CF patients in production of counter-regulatory cytokines (IL-10,
IFN-gamma) and redox metabolism. In the arena of clinical research, as a
member of the CFF Therapeutics Development Network our research group
conducts many trials. I have a particular interest in the field of aerosol
gene therapy for in vivo correction of genetic lung disease, focusing on
AAV-CFTR transfer for CF. We are also investigating new treatments for CF
complications such as diabetes and osteoporosis, Internet-based disease
management, and trials of asthma drugs.
Kari Nadeau, MD, PhD, Pediatrics -- Allergy & Clinical Immunology
Our research interests in the laboratory focus on the role of human T cells,
specifically natural regulatory T cells (Treg) and invariant natural killer
T (iNKT) cells, in immunological diseases. We aim to differentiate the
mechanisms of action of regulatory T cell suppressive function. We study
how cells, such as iNKT cells, disrupt Treg suppressive function and how
chemokines, like lymphotactin, enhance Treg suppressive function. As
Principal Investigator, I have been working in the field of T cell
tolerance for more than 15 years and I hypothesize that disruptions in the
normal maintenace of tolerance by T cells lead to some human
immune-mediated diseases. Our projects involve studying T cell functional
mechanisms involved in the pathophysiology of human diseases such as
allergic asthma, atopic dermatitis, systemic juvenile idiopathic arthritis,
and primary immunodeficiencies. At Stanford, our laboratory is in a unique
position, compared to other institutions, to effect translational
scientific discoveries in these specific diseases since we have peripheral
blood, tissue biopsies, and plasma from over 9 clinical studies occurring
at Stanford. Our laboratory has many joint projects with other
laboratories at Stanford such as the Mellins laboratory, the Lewis
laboratory, and the Herzenberg laboratory.
Mindie H. Nguyen, MD, MAS, Assistant Professor, Gastroenterology and Hepatology
Epidemiology, Pathogenesis, and treatment of hepatitis B, hepatitis C, and hepatocelular carcinoma.
Vu Nguyen, Bone Marrow Transplantation
Regulatory T cells (Treg) have been shown to suppress graft-versus-host
disease (GVHD) without abrograting the beneficial graft-versus-tumor effect
in murine models of hematopoietic cell transplantation (HCT) for hematologic
malignancies. The mechanisms of immunoregulation, in particular, the
allorecognition properties of Treg, their effects on and interaction with
other immune cells, and their thymic and peripheral generation, remain
unclear. We are investigating the localization and homing of Treg in the
setting of allogeneic transplantation and tumor immunity; the mechanism by
which Treg control GVHD without losing the crucial graft-versus-tumor
effect following HCT; and their repertoire development in the thymus
following HCT. The long term interest is the potential application of Treg
immunotherapy in human clinical trials of hematopoietic cell and organ
transplantation.
Mark Nicolls, Medicine,
Pulmonary and Critical Care Medicine
Research interests: 1. Transplantation Immunology, 2. Autoimmune Basis of Pulmonary Hypertension, 3. Inflammation, microvasculature and airway fibrosis.
Garry Nolan, PhD, Associate Professor, Microbiology & Immunology
Control of T cell signaling, machine learning of signaling states by Systems Biology, leukemia/cancer autoimmunity, and HIV-1 are prominent in our studies. We use advanced Flow Cytometric analysis (FACS) of phosphoproteins in single cells and dominant effector genetics to achieve many of our goals. For this we have developed a range of FACS assays, cDNA and peptide expression systems using viruses, and single-cell genetic selections, to study pathways of interest to us.
Signaling systems can now be analyzed directly by flow cytometry and Fluorescence Activated Cell Sorting. We have developed a series of methods for following multiple phosphoproteins in complex populations of primary cells. Up to 11 simultaneous parameters can be followed in single cells including multiple kinases, phosphoproteins, cell cycle, and other parameters allow for exacting resolution of cellular activation states.
We are using these techniques to study B and T cell signaling, dendritic cell function, and other immune parameters by analysis of biochemical functions at the single cell level and have recently used the approach to distinguish predictive patterns of intracellular signaling to classify patient responses to chemotherapies.
In other approaches, termed DOMINANT EFFECTOR genetics, have a variety of utilities in basic and biomedical arenas. We use the systems for studies of NFAT/Rel signaling and developmental progression in the immune system. Retroviral library approaches allow for the genetic selection of molecules that have dominant effects on intracellular signaling and disease pathogenesis. Other systems under study include apoptosis, NFAT, HIV-1 attachment, TNF-alpha and Fas signaling, oncogenic progression, and differentiation inhibitors.
Mark Musen, MD, PhD, Professor, Stanford Medical Informatics
Dr. Musen is Professor of Medicine (Biomedical Informatics) and Computer Science (by courtesy) at Stanford University, where he is head of the Stanford Center for Biomedical Informatics Research. He holds an MD from Brown University and a PhD from Stanford.
Dr. Musen conducts research related to intelligent systems, the Semantic Web, reusable ontologies and knowledge representations, and biomedical decision support. His long-standing work on a system known as Protégé has led to an open-source technology now used by thousands of developers around the world to build intelligent computer systems and new computer applications for e-science and the Semantic Web. He is known for his research on the application of intelligent computer systems to assist health-care workers in guideline-directed therapy and in management of clinical trials. He is principal investigator of the National Center for Biomedical Ontology, one of the seven National Centers for Biomedical Computing supported by the NIH Roadmap.
In 1989, Dr. Musen received the Young Investigator Award for Research in Medical Knowledge Systems from the American Association of Medical Systems and Informatics. He received a Young Investigator Award from the National Science Foundation in 1992. In 2006, he was recipient of the Donald A. B. Lindberg Award for Innovation in Informatics from the American Medical Informatics Association. Dr. Musen sits on the editorial boards of several journals related to biomedical informatics and computer science. He is co-editor of the Handbook of Medical Informatics (Springer-Verlag, 1997) and co-editor-in-chief of the journal Applied Ontology.
Peter Parham, PhD, Professor, Structural Biology and Microbiology & Immunology
Our interest is the function, genetics and evolution of a variable family of natural killer cell receptors that recognize polymorphic determinants of major histocompatibility complex (MHC) class I molecules. These killer cell immunoglobulin-like receptors (KIR) evolve so rapidly that they exhibit much species-specific character and in humans we observe extensive differences between individuals and populations. The interactions between KIR and MHC class I influence the development of the NK cell repertoire and the strength and specificity of the effector response. Combinations of particular KIR and their cognate HLA class I factors are associated with a wide range of clinical effects, including resistance to viral infection, susceptibility to autoimmunities, favourable outcome of hematopietic cell transplantation and reproductive success. Studies on other primate species allow us to define both the common threads to the KIR: HLA class I interaction and that which is uniquely human.
Julie Parsonnet, MD, Professor, Infectious Diseases, Health & Research Policy
I am interested in how a lifetime's exposure to infectious agents affects chronic disease incidence as well as how an individual's infectious diseases history affects their response to acute and chronic infectious challenges. Other work includes studies of infectious causes of cancer (particularly H. pylori), the affect of diabetes on immunity, and studies of risk factors for diarrheal diseases.
Elisabetta Viani Puglisi, PhD, Researcher, Structural Biology
My research focuses on the role of RNA in HIV replication. My current
research investigates the structural basis for initiation of reverse
transcription in HIV, using both NMR spectroscopy and x-ray diffraction
methods.
Jodi Puglisi, PhD, Professor, Structural Biology
My global research probes the role of RNA in biological processes. We study how translation is regulated by viral infection by using a range of structural, biophysical and biochemical methods. We are currently focusing on sensing of viral RNA by the protein kinase PKR.
David A. Relman, MD, Associate Professor, Infectious Diseases, Geographic Medicine and Microbiology and Immunology
My current research is directed towards the characterization of the human indigenous microbial communities of the mouth and gut, with emphasis on understanding variation in diversity, succession, the effects of perturbation, and the role of these communities in chronic periodontitis and inflammatory bowel disease. By understanding the patterns of diversity associated with human health, we may be able to preserve and restore health more effectively. By recognizing the early signs of impending disturbance, we may be able to predict and avoid disease. Experimental approaches include molecular phylogenetics, ecological statistics and metagenomics. A second area of research examines the classification structure of humans and non-human primates with systemic infectious diseases, based on genome-wide gene transcript abundance patterns from blood and other tissues. The goals of this work are to recognize classes of pathogen and predict clinical outcome at early time points in the disease process, as well as gain further insights into virulence (e.g., of variola and monkeypox viruses). See http://relman.stanford.edu
William H. Robinson, MD, PhD, Assistant Professor, Immunology & Rheumatology
The Robinson laboratory studies the molecular mechanisms of and develops
therapies to treat autoimmune disease, with a focus on rheumatoid
arthritis and multiple sclerosis. The mechanisms underlying the
initiation and progression of RA and MS remain poorly understood, and
current therapies are inadequate. We develop and apply
nanotechnologies, including protein micoarray and lipid microarry
technologies, to: (i) discover and define pathogenic autoantigens, (ii)
study the mechanisms governing immune tolerance, and (iii) develop
antigen-specific tolerizing therapies. Our laboratory performs
translational bench-to-bedside research, with the objective of rapidly
converting discoveries at the bench into practical patient care tools
and therapies.
Stanley G. Rockson, MD, Chief, Consultative Cardiology, Director, Ctr for Lymphatic and Venus Disorders Our laboratory is devoted to the study of lymphatic biology and to the phenomena of lymphatic regeneration and therapeutic lymphangiogenesis. We are attempting to characterize molecular and histological attributes of the tissue biology of lymphatic microvastcular dysfuntion, and its responsiveness to biological and pharmacological manipulation. Some translational clinical investigation is also unerway.
Peter Sarnow, PhD, Professor, Microbiology & Immunology
Our laboratory has been been studying the mechanism by which a liver-specific microRNA, miR-122, regulates the amplification of the hepatitis C virus (HCV) genome in cultured cells. Specifically, we have found that miR-122 interacts with the 5' end of the viral RNA and is essential for viral replication. Consequently, sequestration of miR-122 by antisense-oligonucleotides results in rapid loss of viral RNA. We are currently examining the mechanism by which miR-122 helps HCV RNA replication and are searching for cellular targets of miR-122 and their regulation by miR-122. These lines of investigations will lead to new insights how these small noncoding RNAs regulate expression of cellular and viral mRNAs and may point to new venues for antiviral therapeutics against HCV.
Minnie Sarwal, MD, MRCP, DCH, PhD, Associate Professor, Pediatrics-Nephrology
Translational research into the molecular and immunological basis of transplant dysfunction. Using competitive quantitaive RT-PCR and immunohistochemistry, granulysin was identified as a novel peripheral blood marker for transplant rejection, and its distribution in tissue defined steroid resistance or sensitivity. Prospective screening studies are underway to define this as a predictive assay for subclinical rejection.
cDNA Microarray analysis is being conducted on blood and tissue specimens in patients undergoing steroid based and a novel steroid free immunosuppression protocol (designed by Drs Sarwal and Salvatierra at Stanford). Samples are simultaeously hybridized to 23,000 human cDNA's (with about 40% of these cDNA's being unidentified novel genes) in collaboration with Dr. Pat Brown at Stanford.
New mechanisms and genes are being identified for acute rejection, chronic rejection and drug nephrotoxicity. This information may allow for clearer differentiation between these varying causes of transplant dysfunction, without biopsy analysis and also offer means to individualizing immunotherapy for transplant patients.
John Scandling, MD, Professor, Nephrology
Clinical renal transplantation; acute renal failure; cardiovascular disease in diabetic end-stage renal disease.
Gary Schoolnik, MD, Professor, Infectious Diseases, M&I
Structure-function analysis of bacterial adhesion proteins and toxins; design and synthesis of synthetic antigens; immunobiology of human papillomaviruses
Sonja Schrepfer, MD, Instructor, Cardiothoracic Surgery
Dr. Schrepfer's insterests arein hjeart and lung transplantation: Th17 cells, modifying immunosuppression (identifying new targets), inhaled immunosuppression for lung transplant patients, immunobiology of stem cell transplantation (adult and embryonic).
Linda D. Shortliffe, MD, Professor and Chair, Urology
Linda Shortliffe has had nationally funded research in the areas of prostatitis, urinary tract infections, hormonal effects on the urinary tract, and pediatric urinary tract imaging and physiology. Her current research interests include the pathophysiology of urinary tract infections and hydronephrosis, effect of hormones on the urinary tract, and imaging of the dilated urinary tract.
Robert Siegel, MD, PhD, Associate Professor, Microbiology & Immunology
My work is primarily involved in medical education and curricular development, especially in the areas of infectious disease, virology, HIV, and molecular biology. Projects included electronic applications to science education, three dimensional model building, service learning, and the development of undergraduate research projects.
Upinder Singh, MD, Assistant Professor, Internal Medicine and Microbiology
Our lab studies the molecular basis of pathogenesis of a medically important parasite, Entamoeba histolytica. The work is aimed at understanding the virulence determinants that E. histolytica utilizes in causing invasive colonic and hepatic disease. Using a combination of genetic and genomic approaches we are identifying novel mechanisms that the parasite has developed for invading the human host. Additionally, we study the epidemiological trends of of amebic infection, with the goal of identifying a parasite molecular signature that correlates with invasive potential.
Alfred M. Spormann, PhD, Professor, Chemical Engineering and Civil & Environmental Eng
Current research in the Spormann laboratory is directed at understanding of the mechanistic links between molecular, cellular, and population level processes that control the activities and success of microorganisms in natural and human environments. One research thrust is focused on the molecular basis and persistence of microbes in biofilms, and the development of novel classes of antimicrobial agents for treating biofilm-related diseases. Other projects, in collaboration with physicians in the medical school, investigate the metabolic basis and adaptive evolution of microbes in the urinary and intestinal tract, and their dynamic changes associated with chronic infections and perturbations.
Randall S. Stafford, MD, PhD, Associate Professor, Prevention Research Center
As Director of the SPRC Program on Prevention Outcomes and Practices, my research aims to advance scientific understanding of the forces that influence physician and patient behavior. One focus of investigation is on medication use, including the quality of prescribing patterns, health policy and drug regulation, and innovation in pharmacotherapy. While off-label prescribing presents a regulatory, economic, and clinical research challenges, it is also a vital source of innovation, particularly for immune modulating drugs.
Larry Steinman, MD, Professor, Neurology, Neurological Sciences, Pediatrics and Genetics
Autoimmunity: pathogenesis and new treatments.
David A. Stevens, Professor, Infectious Diseases
Dr. Stevens' group studies the biology, immunology, epidemiology and therapy of fungal infections. They are using molecular fingerprinting systems applied to the genomes of Candida species to develop tools to allow typing and differentiation of clinical isolates and for epidemiological and taxonomic purposes. Animal models are developed and used to study differences in virulence in fungal strains, their biochemical characterization and interaction with host defenses, particularly the role of therapy with recombinant cytokines and other immunomodulators. The infections most intensively investigated, with respect to pathogenesis, are coccidioidal meningitis and pulmonary blastomycosis. The laboratory is working on development of vaccines against Coccidioides and Aspergillus. The chemotherapy of fungal infection is also under study including the mechanisms of resistance to current agents and the evaluation of agents with new mechanisms of action, in animal models and in human disease. The laboratory is, in addition, a clinical reference laboratory for fungal and actinomycete susceptibility testing, and body fluid antifungal drug concentration determinations, for hospitals in the area. In Latin America, the researchers are involved in the study of paracoccidioidomycosis and other endemic mycoses. Mammalian estradiol influence on Paracoccidioides pathogenesis is being investigated by focusing on the block of morphogenetic transformation and the role of the fungal binding protein. Paracoccidioides gene expression during morphogenesis, and the events in hormone-mediated block, are under study with DNA microarray technology.
Samuel Strober, MD, Professor, Medicine, Immunology & Rheumatology
Immune Tolerance in organ and bone marrow transplantation, and regulatory T cells. Molecular and cellular mechanisms in the pathogenesis of systemic lupus erythematosus.
Karl G. Sylvester, MD, Assistant Professor, Surgery, Pediatric Surgery
My laboratory studies the various molecular and cellular mechanisms of post-natal liver regeneration. We are particularly interested in identifying post-natal liver progenitor and stem cells as well as the signaling pathways that regulate their proliferation and differentiation. Recently we have identified a role for Wnt/b-catenin signaling in liver progenitor cell biology during periods of chronic injury. We are identifying critical genes and cell surface markers as targets of this pathway in the relevant cell populations. Our longer term goals include exploiting these signaling pathways toward developing liver cell therapies. In a related manner, we are also interested in how these progenitor cells and signaling pathways may be involved in hepatic tumorigenesis in human liver tumors. Once again the objective of this work is to identify potential molecular targets for liver tumor therapies.
Daniel Sze, MD, PhD, Associate Professor, Interventional Radiology
Transarterial administration of chemotherapeutics, radioactive microspheres, and biologicsfor the treatment of unresectable tumors; Stent and Stent-graft treatment of peripheral vascular diseases, aneurysms, aortic dissections; management of portal hypertension (TIPS); Percutaneous treatment of complications of organ transplantation; Venous reconstruction; Magnetic resonance imaging-guided interventions.
Man-Wah Tan, PhD, Assistant Professor, Genetics, Microbiology & Immunology
Host-pathogen interactions are complex: they involve virulence determinants produced by pathogens and varied defense mechanisms deployed by the host. Determining the genetic factors involved in each side of the interaction is therefore crucial to understanding pathogenesis. We use infection of the nematode C. elegans by the human pathogens Pseudomonas aeruginosa, Salmonella enterica and Enterococcus faecalis as the experimental system to study host-pathogen interactions. Among the questions we are currently addressing are: 1) How do epithelial GATA transcription factors regulate inducible immune responses in C. elegans and human lung epithelial cells? 2) How does the neuroendocrine system influence the coordination and efficiency of the innate immune system, and what is the biological significance of neural modulation of immune function in vivo? 3) How does aging affect the competence of innate immune responses? 4) How are immune signaling modules coordinated within the host? 5) How do polyunsaturated fatty acids affect immune function? and, 6) How does P. aeruginosa subvert C. elegans immune responses?
Rabindra Tirouvanziam, PhD, Research Associate, Herzenberg Laboratory, Genetics
My broad interests are in the study of inflammatory function, metabolic and redox homeostasis, as they relate to human pathologies. My approach is grounded in basic research, using an array of cellular and molecular assays applied to clinical samples, in vitro models, as well as mouse and Drosophila model systems. Part of my work is dedicated to the development of cutting-edge single-cell assays using multiparametric flow cytometry. My commitment is also to translational research, working in collaboration with clinicians to explore new therapeutic avenues for the fatal lung disease cystic fibrosis (CF). Recent work include the design and implementation of a phase 1-2a-2b clinical trial of high-dose oral N-acetylcysteine as a systemic anti-inflammatory strategy in CF. I am also actively pursuing basic research in other human diseases besides CF, including asthma, chronic obstructive pulmonary disease and more recently, autism.
Philip S. Tsao, PhD, Associate Professor, Cardiovascular Medicine
The major focus of our laboratory deals with intracellular signaling and transcriptional regulation of chronic cardiovascular disorders such as atherosclerosis. Recently, our efforts have concentrated on the role of insulin resistance, obesity, and type 2 diabetes. We have also collaborated with colleagues in Vascular Surgery to investigate the etiology of a particular variant of atherosclerosis, namely abdominal aortic aneurysms. Given that inflammation has been postulated to play a major role in all of these metabolic disturbances, we have a significant interest in understanding the underlying immune mechanisms. While the majority of our work up to this point has been performed in preclinical animal and cell culture models, we have expended considerable effort to translate these concepts to human biology. As such, we have an ongoing effort to accurately phenotype individuals with these clinical issues and have isolated tissue samples (e.g., blood, adipose tissue) in order to perform proteomic, genomic and genetic association studies.
PJ Utz, MD, Associate Professor, Immunology & Rheumatology
We are part of the Department of Medicine, Division of Immunology at Stanford University School of Medicine. Our lab is located in the brand new CCSR building, room 2215. We are interested in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), scleroderma, myositis, primary biliary chirosis (PBC), Sjogren's disease, insulin dependent diabetes (type I diabetes or IDDM), multiple sclerosis (MS) and mixed connective tissue disease (MCTD). The Utz lab is comprised of approximately 12 scientists, including Postdoctoral Fellows, Research Assistants, Undergraduate Students and Graduate Students. The focus of our research centers on serum autoantibodies produced in a variety of autoimmune diseases. In addition to trying to better understand the pathogenic mechanisms involved in autoimmunity, we are interested in developing bench-to-bedside technologies, including diagnostics and therapeutics, for human autoimmune diseases.
Hannah Valantine-von Kaeppler, Professor , Cardiovascular Medicine
My lab is focused on understanding the mechanism mediating acute and chronic allograft failure, in particular on the role of microvascular injury in acute allograft failure and the mechanisms of mediating transplant coronary artery disease.
Cliff Wang, Assistant Professor of Chemical Engineering
We are investigating how multiple genes, molecules, or pathways cooperate to govern a cell's behavior. For example, how is it that multiple mutations are necessary for cell transformation? How is it that two or more co-stimulatory signals are necessary for cell activation? To answer these questions, we are developing gene expression tools to study transformation and proliferation of B and T lyphocytes.
We are also studying how activation and inactivation of genes affect mutation frequency. Mutator phenotypes lead to tumorigenesis and possibly also inflammatory and autoimmune disease. To investigate the role of somatic mutations in these diseases, we are developing reporter genes to monitor mutation rates and genome instability.
Joseph C. Wu, MD, PhD, Assistant Professor of Medicine & Radiology
Our lab works on gene therapy, stem cell biology, and molecular imaging. We use different molecular markers to better understand stem cell biology in vivo. These include monitoring stem cell survival, proliferation, and differentiation. We also use gene and microRNA profiling to understand human embryonic stem cell differentiation.
Tony Wyss-Coray, PhD, Associate Professor, Neurology & Neurological Sciences
Our lab tries to understand neurodegeneration and neurological disease in the context of immune responses. We are pursuing the hypothesis that altered or failing immune responses might underlie or at least contribute to age-related degenerative diseases of the nervous system. We use mouse genetics, behavior, cell culture, and proteomic approaches to try to test this hypothesis.