Meet The Molecular Pathogenesis Faculty

Amy C. Anderson, Ph.D.
Assistant Professor of Chemistry
Amy.Anderson@Dartmouth.edu

Work in the Anderson lab focuses on aspects of structure-based drug design against pathogenic drug targets. Using a combination of techniques including X-ray crystallography, molecular modeling and biochemistry, we elucidate the protein:ligand interactions between drug targets and their inhibitors. Currently we are developing inhibitors of dihydrofolate reductase from two pathogenic organisms, Cryptosporidium hominis and Toxoplasma gondii.

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David J. Bzik, Ph.D.
Professor of Microbiology & Immunology
David.Bzik@Dartmouth.edu

Our work focuses on drug and vaccine development for treatment and prevention of Toxoplasmosis, the third most common foodborne infectious disease in the United States . Our current research efforts involve dissecting the molecular mechanisms that enable Toxoplasma gondii to steal a variety of essential resources from the host and to manipulate the host immune response to gain permanent rent-free residence in host tissues. Toxoplasma gondi has emerged as the most important current model system for studying biology of intracellular protozoan parasitism and host immune response. The research encompasses studies on drug discovery in pyrimidine and purine acquisition pathways as well as host responses affecting establishment of protective immunity and parasite persistence. These studies are generally applicable to other serious infectious diseases such as malaria, a parasitic infection that kills more than two million young children every year while also causing serious infections in 300 to 400 million adolescents and adults.

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Ambrose Cheung, M.D.
Professor of Microbiology & Immunology
Ambrose.Cheung@Dartmouth.edu

Our work focuses on the regulation of virulence determinants in Staphylococcus aureus, a bacteria pathogen that has gained notoriety because of its prevalence and increasing antibiotic resistance in human infections. We employ genetic, biochemical, structural and in vivo approaches to assess the expression of virulence genes in animal models and contrasting them to laboratory conditions. We are particularly interested in virulence genes that are expressed in response to clues from stresses, host factors and those involved in cell wall synthesis and lysis. In combining these approaches, we seek to identify novel targets for the development of antimicrobial therapy.

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Kathryn Cottingham, Ph.D.
Associate Professor of Biology
Kathryn.Cottingham@Dartmouth.EDU

Cholera is an infectious disease that is a more persistent and global health problem now than it was a few decades ago. Cholera is caused by the bacterium Vibrio cholerae , which was once thought to be unable to survive for more than a few days outside mammalian intestines, but is now known to be an abundant natural component of freshwater and estuarine systems around the world. In collaboration with Ron Taylor's group, we are currently using V. cholerae as a model bacterium to understand bacterial pathogen dynamics in aquatic ecosystems.

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Michael W. Fanger, Ph.D.
Professor of Microbiology & Immunology, and Medicine
Michael.Fanger@Dartmouth.edu

Research in Dr. Fanger's laboratory is focused on studies of the role of human myeloid cells (macrophages and granulocytes) and dendritic cells in tumor cell killing and in the development of immunity to tumors and pathogens. Using bispecific antibodies, he has studied the targeted killing of human tumors in vitro, studies that have led to human clinical trials with promising results. Moreover, since myeloid and dendritic cells are antigen presenting cells (APCs) that play a major role in the development of immunity, fusion proteins have been developed that target tumor antigens to these APCs. This approach has demonstrated, in vitro and in animal models, that targeting antigens to certain molecules on APCs significantly enhances processing and presentation of antigen and results in significantly enhanced immunity to the targeted antigen. Studies are now ongoing that would use targeted tumor associated antigens as vaccines for therapy of human tumors.

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James D. Gorham, M.D., Ph.D.
Associate Professor of Pathology, and Microbiology & Immunology
James.D.Gorham@Dartmouth.edu

The major research goal in our laboratory is to define the mechanisms by which the cytokine transforming growth factor-beta-1 (TGF-b1) regulates inflammatory immune responses. We use a variety of genetic, cellular, and molecular approaches to interrogate the role of TGF-b1 as a master regulator of immunity, both at the level of the whole organism, and at the level of the individual leukocyte.

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William R. Green, Ph.D.
Professor and Chair of Microbiology & Immunology
Bill.Green@Dartmouth.edu

Our research contributions center on obtaining a better understanding of the interplay between retroviruses and the immune system, especially killer T cells that are able to eliminate virus infected cells. We focus on defining unique viral antigens recognized by these T cells and how the virus attempts to evade the immune system. Along with investigations as to how to increase the immunogenicity of viral antigens via the innate immune system, including defining approaches towards a safer vaccination against smallpox , this research should have important implications for vaccine design and possibly immunotherapeutic approaches.

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Mary Lou Guerinot, Ph.D. 
Professor of Biological Sciences
Mary.L.Guerinot@Dartmouth.edu

One of the main goals of our research is to understand how the bacterial symbiont Bradyrhizobium japonicum interacts with its host plant soybean to regulate metabolic processes essential for the nitrogen-fixing symbiosis. Experiments underway in our lab should help elucidate how bradyrhizobia adapt to life as intracellular bacteria. Information from our studies may also be relevant to other bacteria with intracellular lifestyles, such as the animal pathogens Legionella and Brucella.

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Paul M. Guyre, Ph.D. 
Professor of Physiology, and Microbiology & Immunology
Paul.Guyre@Dartmouth.edu

Studies in our laboratory focus on iteractive mechanisms of hormone and cytokine regulation of immune function. Our goal is to better understand mechanisms that regulate macrophage and dendritic cell activation in inflammation, sepsis, autoimmunity and cardiovascular disease.

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Deborah Hogan, Ph.D.
Assistant Professor of Microbiology & Immunology
Deborah.A.Hogan@Dartmouth.edu

The research in our lab focuses on the molecular analysis of interactions between microorganisms. The interactions that occur between microbes within the human body are central to both human health and disease. For example, the synergy between organisms within the normal microflora provides an important protective barrier against potential pathogens. At the same time, many illnesses, such as respiratory and genital infections, gastroenteritis, and periodontal diseases, often involve multiple microorganisms. Our goal is to identify key elements of microbe-microbe interactions in order to develop novel strategies for manipulating microbes and microbial communities in beneficial ways.

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Lloyd H. Kasper, M.D.
Professor of Medicine and of Microbiology & Immunology
Lloyd.Kasper@Dartmouth.edu

The research focus of this laboratory is on the immune response to and cell biology of Toxoplasma gondii . This parasite which is perhaps the most common parasitic infection of humans causes congenital disease in the newborn and is the primary cause of CNS infection in those with AIDS. Our research effort has been directed at understanding the interaction between the parasite and its host. Toxoplasma is able to stimulate both a host protective response and downregulate the immune system in order to survive. Our long term effort is to understand the mechanims of innate immunity to this opportunistic pathogen and how the host protects itself against recurrent chronic infection. A variety of immunologic and molecular approaches are utilized to decipher these events during invasion and internalization. Our second area of interest is on the immunology of multiple sclerosis. The long term effort for these studies is to evaluate the ability of novel immunologic tools, in particular inhibitors of T cell activation on the ability to block disease at the molecular and clinical level.

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Randolph J. Noelle, Ph.D.
Professor of Microbiology & Immunology
Randy.J.Noelle@Dartmouth.edu

In 1991, my laboratory identified a novel membrane protein expressed on helper T lymphocytes (Th), CD154. The receptor for CD154 is CD40. CD40 is expressed on B lymphocytes and antigen-presenting cells. This ligand-receptor pair plays a central role in the control of antibody- and cell-mediated immunity. Intervention in CD154-CD40 interactions (by genetic deletion or antibody-blockade) can block a wide spectrum of immune and autoimmune responses as well as transplantation rejection. As a result, the laboratory has focused on four areas of immunobiology that are relevant to CD40 function.

CD40 signaling. For the past 6 years we have been actively involved in trying to unravel the biochemical signaling cascade that transpire as a consequence of CD40 signaling. We have produced a set of Tg mice that have defined mutations in the cytoplasmic domain of CD40.

Inflammation in the CNS. Since early in the CD154 story, we have been involved in deciphering its role in inflammation. Studies have clearly shown that one can readily prevent disease development, as well as intervene in disease progression. Our efforts now and into the future are to understand the relationship between the peripheral immune system and the immune system within the CNS in controlling T cell recruitment, tolerance and inflammation.

B cell memory and plasma cell development. Our goals are to understand the factors that control the remarkable longevity of plasma cells and memory B cells in mice. Studies using global gene analysis have and will lead to novel genetic targets that allow us to understand the mechanisms that allow the persistence of these cells in humans for decades.

Immune tolerance in transplantation. Perhaps the most impressive activity of ±CD154 is its ability to block the rejection of fully allogeneic skin, heart, kidney and islet allografts in mice, and in some of these cases in monkeys. Exciting new insights into how ±CD154 induces peripheral T cell tolerance and long-lived graft acceptance have emerged from these studies. The impact of ±CD154 on T cell anergy, regulatory T cell function, and dendritic cell biology are all elements in engendering permanent allograft survival.

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George A. O'Toole, Ph.D.
Assistant Professor of Microbiology & Immunology
George.O'Toole@Dartmouth.edu

Our work focuses on the formation of surface-attached microbial communities known as biofilms. Once these microbial communities form they are highly resistant to antibiotics. The formation of biofilms of organisms such as Staphylococcus aureus and Pseudomonas aeruginosa on a variety of medical implants (such as catheters, contact lenses and artificial joints) and their resistance to treatment by standard antibiotic therapy represents an important clinical problem that costs the healthcare system over $1 billion dollars annually.

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C. Fordham von Reyn, M.D.
Professor of Medicine, Chair, Infectious Diseases Section, DHMC
C.Fordham.von.Reyn@Dartmouth.EDU

Dr. von Reyn's research focus is HIV-associated tuberculosis in the developing world. He is PI for an NIH-funded Phase III trial of a new TB vaccine for HIV positives based in Tanzania and PI for a Fogarty AIDS International Training and Research Program between Dartmouth Medical School and the Muhmibili University College of Health Sciences in Dar es Salaam , Tanzania .

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Joseph D. Schwartzman, M.D.
Professor of Pathology & Director of Clinical Microbiology
Joseph.D.Schwartzman@Dartmouth.EDU

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Nancy A. Speck, Ph.D.
Professor of Biochemistry
Nancy.Speck@Dartmouth.edu

My laboratory studies a family of transcription factors called core-binding factors (CBF). CBFs are comprised of two subunits, one which binds DNA directly (CBFa), and a second subunit, CBFß, that associates with CBFa subunits and increases their affinity for DNA. Three genes in mammals encode CBFa subunits, all of which are essential for mammalian development. One of these, RUNX1 (or AML1) is required for definitive hematopoiesis, and is disrupted by the t(8;21) associated with acute myeloid leukemia of the M2 subtype, and by the t(12;21) in pediatric acute lymphocytic leukemias. The gene encoding the CBFß subunit (CBFB) is disrupted by the inv(16) associated with acute myeloid leukemia, M4 eosinophil subtype. Currently we are using genetic approaches to study the role of Runx1 and CBFß in hematopoiesis in mice. We are also studying the biophysical properties of the CBF subunits and their oncogenic derivatives in collaboration with structural biologists.

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Karen Skorupski, Ph.D.
Associate Research Professor of Microbiology and Immunology
Karen.A.Skorupski@Dartmouth.EDU

Our research focuses on understanding the complex mechanisms utilized by pathogenic bacteria to regulate virulence gene expression in response to environmental stimuli so that better strategies can be developed to control and prevent bacterial infections.

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Paula Sundstrom, Ph.D.
Associate Professor of Microbiology & Immunology
Paula.Sundstrom@Dartmouth.edu

We are discovering fungal specific targets and drugs for treatment and prevention of vaginitis, oral thrush and invasive human diseases caused by the yeast germ Candida albicans . Currently we are focusing on neutralizing the function of a fungal surface protein which forms tight attachments to vulnerable sites on human stratified squamous epithelium. The drugs will be useful for preventing yeast infections in infants, transplant patients, those with malignancies, with HIV infection, with diabetes and numerous others at risk for candidiasis.

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Surachai Supattapone, M.D., Ph.D., D.Phil.
Assistant Professor of Biochemistry and Medicine
Surachai.Supattapone@Dartmouth.edu

Our laboratory works on the pathogenesis of prion diseases such as scrapie and chronic wasting disease. These unusual infectious diseases appear to be caused by a misfolded protein called PrP, and we are studying how PrP misfolding occurs, and kills cells of the brain.

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Ronald K. Taylor, Ph.D.
Professor of Microbiology & Immunology and Genetics
Ron.K.Taylor@Dartmouth.edu

Our work focuses on vaccine and drug development for prevention and treatment of epidemic cholera, which is spread aquatically in unhygienic conditions. Our current efforts involve interference with the production and function of a protein, TcpA, that forms specialized pili on the surface of the marine bacterium, Vibrio cholerae and facilitates infection of humans. The pili allow the bacteria to self-adhere, forming particles that become entrapped within the architecture of the human intestine where the bacteria release cholera toxin, causing severe, life-threatening diarrhea. The research encompasses studies on epitope specific protective immune responses as well as selective drug targets for cholera prevention. The studies are generally applicable to a number of serious infectious diseases such as meningitis, hemorrhagic colitis, sexually transmitted diseases, and infections associated with cystic fibrosis.

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Edward Usherwood, Ph.D.
Assistant Professor of Microbiology & Immunology
Edward.J.Usherwood@Dartmouth.edu

The goal of my laboratory is to have a better understanding of the relationship between the immune reponse and chronic virus infections. We study gammaherpesviruses, which can give rise to tumors in the immunosuppressed and AIDS patients. This knowledge will lead to better vaccines and immunotherpies to combat this important class of persistent virus infections.

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Charles R, Wira, Ph.D.
Professor of Physiology
Charles.R.Wira@Dartmouth.EDU

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