Heads of Laboratories
James G. Krueger, M.D., Ph.D.
Director, Milstein Medical Research Program
Senior Attending Physician
D. Martin Carter Professor in Clinical Investigation
Laboratory of Investigative Dermatology
Psoriasis, which is caused when the body’s immune system attacks the skin, is one of the most accessible human diseases in which to examine both cellular and molecular pathogenesis of T cell mediated autoimmunity. Dr. Krueger uses histological and genomic approaches to study psoriasis as a model Th17 inflammatory disease. His work has implications for other common T cell mediated inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, which have similar immunological phenotypes.
Dr. Krueger’s group focuses on the study of cutaneous inflammation and autoimmune mechanisms in human skin. Their research is fundamentally rooted in “bench-to-bedside” science, combining the clinical study of new medical therapeutics with laboratory study of relevant immunopathogenic mechanisms in human cells and tissues. The Krueger laboratory conducts clinical research on patients with psoriasis vulgaris within The Rockefeller University Hospital. They treat patients with a wide variety of engineered immune agonists or antagonists in order to stimulate or inhibit molecular control points for the restoration of normal immune responses. By combining novel immune-directed therapeutics with large-scale study of gene expression (using gene chips and real-time RT-PCR reactions), an approach called pharmacogenetics, they seek to elucidate the molecular pathways that cause pathogenic inflammation and regulate normal human immune responses.
More experimental immunotherapeutics have been assessed in clinical studies in psoriasis than any other human inflammatory disease. Dr. Krueger’s group has pioneered a number of successful treatments, including some that act on T cells, one that antagonizes specific inflammatory cytokines and one that utilizes a type of ultraviolet light with immunomodulatory properties.
The lab-based research accompanying Dr. Krueger’s clinical trials includes the study of T cell, dendritic cell and keratinocyte activation responses using techniques such as cell culture, flow cytometry and biochemical analysis. His group is also studying expression of a defined set of proinflammatory genes through real-time PCR and many other genes through genome-wide statement studies using DNA arrays. They defined the first disease classification set for psoriasis using chip-based approaches and recently determined a specific genetic and immunological signature that differentiates psoriasis from the closely related skin disorder called atopic eczema.
Dr. Krueger’s research in healthy skin showed that a previously unknown population of dendritic cells exists alongside macrophages in the skin. Other recent work by members of the Krueger lab showed that a newly discovered immune cell, Th17, plays a central role in psoriasis and could serve as a target for future therapies. And by investigating the contribution of activated T lymphocytes, Dr. Krueger has found that psoriasis may be induced by tissue-infiltrating T lymphocytes, which trigger keratinocytes into a physiologically regulated wound repair pathway of hyperplasia and altered differentiation.
In order to place inflammatory pathways discovered in psoriasis in the context of other T cell mediated diseases and tissue rejection responses, the team has been collaborating with investigators of other inflammatory cutaneous diseases (e.g., atopic dermatitis, sarcoidosis and autoimmune alopecia) and graft-versus-host disease. They are attempting to define molecular pathways that control normal and pathogenic cellular immune responses in order to broaden our understanding of organ-specific autoimmune diseases.
Dr. Krueger received his bachelor’s degree from Princeton University in 1979, his Ph.D. from The Rockefeller University in 1984 and his M.D. from Cornell University Medical College in 1985. He came to Rockefeller as a guest investigator in the Laboratory for Investigative Dermatology, was appointed assistant professor in 1990, associate professor and head of lab in 1995 and professor in 2003. Dr. Krueger has held positions at The Rockefeller University Hospital since 1989. In 2006 he became codirector of the Center for Clinical and Translational Science, established by a Clinical and Translational Science Award from the National Center for Research Resources of the National Institutes of Health. Dr. Krueger was medical director and program director of the General Clinical Research Center from 1996 to 2006 and currently directs the Milstein Medical Research Program, which conducts new clinical studies of the pathogenesis of melanoma and other pigmentory diseases.
In 2010 Dr. Krueger won the Astellas Award in Public Health from the American Academy of Dermatology as well as the Farber Award from the Society of Investigative Dermatology. In 2006 Dr. Krueger received the E.H. Ahrens Jr. Award for clinical research from the Association for Patient-Oriented Research. He is also a recipient of two awards from the American Skin Association: the Distinguished Achievement Award and the Psoriasis Research Achievement Award, both granted in 2001. Dr. Krueger is a member of the American Society for Clinical Investigation and the Association of American Physicians.
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