Lab Interests

Our laboratory studies the way in which human cellular proteins control the replication of retroviruses, the family of viruses which includes HIV, the virus which causes AIDS.  We study the interaction between retroviruses and human cellular proteins both to understand how the viruses cause human disease, and to use the viruses as a relatively simple model of human cellular function.  The reason that viruses are a good model in this regard is that they have stolen human proteins to use for their own purposes.  Therefore, if we understand how the viruses have used these human cellular proteins, we will gain an understanding of how these same proteins function in people in health and disease.

            In one of our studies, we identified a protein which interacts with HIV, called DEK.  DEK does not resemble any other protein previously identified.  Intriguingly, DEK has been linked to important human diseases, including leukemias, liver cancer, brain cancer, and melanomas.  DEK is also found on the pathway which is involved in the disease called ataxia-telangiectasia, an inherited disorder which predisposes children to develop cancer.  In addition to its role in cancers, DEK appears to be involved in certain autoimmune disorders, such as juvenile rheumatoid arthritis.  It also may be playing a role in the blinding eye disease that certain children with juvenile rheumatoid arthritis develop.

            In other studies in our laboratory, we have examined the function and mechanism of action of one of the human GLI proteins.  We became interested in this protein when we demonstrated that it can affect the replication of both HIV and its cousin, HTLV-1, a virus linked to leukemia and lymphoma.  GLI proteins are also very important in developmental biology, and so mutations in GLI or alterations in GLI function lead to genetic syndromes in human beings.  Further, GLI proteins have been linked to skin cancers.

            Other studies in our laboratory investigate how Kaposi’s Sarcoma develops in patients.  This disfiguring cancer, which involves the skin and the internal organs, can affect patients with HIV, as well as other patients with weakened immune systems.  Our work has suggested that certain chemicals in the blood, called chemokines, may play an important role in how the blood vessels characteristic of Kaposi’s Sarcoma develop.  These CXC chemokines include IL-8 and GRO-a.  We are currently investigating whether blocking the actions of these specific chemokines will lead to a therapy for Kaposi’s Sarcoma. We have also made the observation that IL-8 and GRO-a stimulate HIV-1 replication, and that blocking their action inhibits HIV-1 replication.  We are currently investigating whether this might present a new approach to therapy for HIV-infected patients.

            In view of the above, our work has the possibility to impact upon the following diseases:

1.      AIDS

2.      Cancer

·        Leukemia

·        Lymphoma

·        Liver cancer

·        Brain cancer

·        Melanoma and other skin cancers

·        Kaposi’s Sarcoma

3.   Autoimmune diseases, including juvenile rheumatoid arthritis and eye disease

4.      Genetic syndromes

            In addition to doing research, our laboratory serves as a training ground for younger scientists who are interested in pursuing a career in medical research.  Trainees in the laboratory have included physicians in fellowships designed to make them Infectious Diseases specialists, postdoctoral fellows with Ph.D.’s, Ph.D. students from both the Immunology and Cellular and Molecular Biology training programs, students from the Medical Scientist Training Program (who are obtaining both the M.D. and Ph.D. degree), students obtaining a Master’s degree in Public Health, and undergraduate students at the University of Michigan.  Our laboratory members all have individual projects, and are urged to take as creative a role as possible and to advance their projects to the cutting edge of biomedical science.  We are funded through multiple grants from the National Institutes of Health, as well as grants from the American Cancer Society and the Arthritis Foundation.  Our goal is to use every technique possible to understand important disease-related biological processes and to apply this knowledge to the pursuit of improved treatment for AIDS, cancer, arthritis, and other diseases.