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. Dr. Krueger’s 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 those that: (1) selectively deplete activated T cells; (2) block early T cell activation signals; (3) block T cell mitogenic receptors; (4) alter T cell differentiation toward regulatory cells; and (5) antagonize specific inflammatory cytokines. They have also pioneered a therapy that uses a type of ultraviolet light (312 nm UVB) with strong immunomodulatory properties, and they continue to study its immunosuppressive mechanisms.

The laboratory-based research that accompanies Dr. Krueger’s clinical trials includes the study of T cell, dendritic cell and keratinocyte activation responses using a variety of techniques (including cell culture, flow cytometry and biochemical analyses). His group is also studying expression of a defined set of pro-inflammatory genes through real-time RT-PCR, and many other genes through genome-wide statement studies using DNA arrays. Recently, they defined a 159-gene “disease classification” set for psoriasis using chip-based approaches, and the lab is now working to determine which of those genes are uniquely expressed in psoriasis and how their expression is regulated.

Dr. Krueger’s lab has identified a number of new cytokines and other inflammatory mediators expressed in psoriasis that could serve as potential therapeutic targets. By investigating the contribution of activated T lymphocytes to the pathogenesis of psoriasis, they have 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, members of the Krueger lab have been collaborating with investigators who study other inflammatory cutaneous diseases (atopic dermatitis, sarcoidosis and autoimmune alopecia) or graft-versus-host disease in human models. They are attempting to define molecular pathways that control normal and pathogenic cellular immune responses, and to use this information to broaden our understanding of organ-specific autoimmune diseases.

CAREER

Dr. Krueger received his bachelor’s degree from Princeton University in 1979, his Ph.D. from Rockefeller University in 1984 and his M.D. from Cornell University Medical College in 1985. That same year he came to Rockefeller as a guest investigator in the Laboratory for Investigative Dermatology, and has been at the university since. He was appointed assistant professor in 1990, associate professor and head of lab in 1995 and professor in 2003. Dr. Krueger also holds positions at The Rockefeller University Hospital, where he was named associate physician in 1989, physician in 1995 and senior physician in 2003. In 2006, Dr. Krueger became co-director of the Center for Clinical and Translational Science, established by a Clinical and Translational Science Award (CTSA) from the National Center for Research Resources of the National Institutes of Health. Dr. Krueger was medical director and program director of the CTSA’s predecessor program, the General Clinical Research Center, from 1996 to 2006.

In 2006, Dr. Krueger received the Ahrens Award for Clinical Research from the Association for Patient-oriented Research. He is also a recipient of two awards from the American Skin Association: a 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.