David Markovitz, M.D.

Professor of Internal Medicine, Division of Infectious Diseases

Biography

David Markovitz is a Professor of Internal Medicine in the Division of Infectious Diseases who also has appointments in the programs in Cellular and Molecular Biology, Cancer Biology, and Immunology.  His laboratory focuses on understanding how human cellular factors control the replication of retroviruses such as HIV.  These studies are performed both to understand the biology of retroviruses and to develop possible therapies for these important human pathogens, as well as to exploit the viruses as a mechanism for understanding human cellular biology.  Current interests in the laboratory focus on four areas: First, the laboratory is studying endogenous human retroviruses, retroviruses that have insinuated themselves into the human genome over the course of millions of years and now make up fully eight percent of our genomes.  The Markovitz laboratory is studying whether, contrary to existing dogma, these viruses can still replicate, as well as investigating the role of these viruses in AIDS, cancer, and other diseases.  A second project deals with the DEK protein, which is involved in cancer causation and the pathogenesis of juvenile arthritis.  Third, the laboratory is working on the molecular engineering of a banana lectin that could be part of a vaginal microbicide used to prevent the sexual spread of HIV and perhaps in the treatment of viral infections.  Lastly, the Markovitz research group is studying the role of the intermediate filament protein vimentin in inflammation.  These studies are carried out in conjunction with a wide variety of Ph.D. and M.D. trainees, as well as in close collaboration with a number of faculty members from diverse departments at the University of Michigan and other institutions.  Dr. Markovitz’s work has been recognized by his election to the two principal honorary societies for academic Internal Medicine physicians, the American Society for Clinical Investigation and the Association of American Physicians.

In addition to his research, Dr. Markovitz is a consultant on the Infectious Diseases service at the University of Michigan and Veterans Hospitals.  He has been married to Ruth Hurwicz Markovitz for 30 years, and they have three wonderful children, Lara, Rebecca, and Adam.  David has a wide range of non-medical interests, and majored in Middle Eastern Studies as an undergraduate.  He has a long-time interest in art, music, movies, novels, and both serious and junky TV.  David has traveled widely, and speaks 3½ languages.

Research Interests

Our laboratory studies the interaction of retroviruses such as HIV with human cellular factors.  The goal of this work is to understand the mechanisms that regulate retroviral replication, and also to use these viruses as models for elucidating human cellular processes. Our work is thus relevant to understanding cancer and immunity, as well as viral pathogenesis.  The specific projects in the laboratory at this time examine the following issues: (1) development of new strategies to treat or prevent retrovirus-associated diseases, (2) the mechanism of action of the DEK protein, which has been linked to the pathogenesis of HIV-2, leukemia, several solid tumors, and autoimmune disease, (3) the role of vimentin in immunity, and (4) pathogenic effects of human endogenous retroviruses.

Publications

Mor-Vaknin, N., Punturieri, A., Sitwala, K., and Markovitz, D.M. Vimentin is secreted by activated macrophages. Nature Cell Biology 5:59-63, 2003.

Mor-Vaknin, N., Punturieri, A., Sitwala, K., Faulkner, N., Legendre, M., Khodadoust, M.S., Kappes, F., Ruth, J.H., Koch, A., Glass, D., Petruzzelli, L., Adams , B.S., and Markovitz, D.M . The DEK nuclear autoantigen is a secreted chemotactic factor. Molecular and Cellular Biology 2006 26(24):9484-9496, 2006.

Khodadoust, M.S., Verhaegen, M., Kappes, F., Riveiro-Falkenbach, E., Cigudosa, J.C., Kim, D.S.L., Chinnaiyan, A.M., Markovitz, D.M.*, and Soengas, M.S*.  Melanoma proliferation and chemoresistance controlled by the DEK oncogene.  Cancer Res. 2009; 69(16):6405-6413.

Kappes, F., Waldmann, T., Mathew, V., Yu, J., Zhang, L., Khodadoust, M.S., Chinnaiyan, A.M., Luger, K., Erhardt, S., Schneider, R., and Markovitz, D.M.  The DEK oncoprotein is a su(var) that is essential to heterochromatin integrity. Genes Dev. 2011; 25:673-678. PMCID: PMC3070930

Mor-Vaknin, N., Kappes, F., Dick, A.E., Legendre, M., Damoc, C., Teitz-Tennenbaum, S., Kwok, R., Ferrando-May, E., Adams, B.S., and Markovitz, D.M.  DEK in the synovium of JIA patients: characterization of DEK antibodies and posttranslational modification of the DEK autoantigen.  Arthritis Rheum. 2011; 63(2):556-567. PMCID: PMC3117121

Contreras-Galindo, R.A., Kaplan, M.H., Contreras-Galindo, A.C., Gonzalez-Hernandez, M., Ferlengui, I., Giusti, F., Lorenzo, E., Gitlin, S.D.,  Dosik, M.H., Yamamura, Y., and Markovitz, D.M. Characterization of human endogenous retroviral elements in the blood of HIV-1-infected individuals. J. Virol. 86(1):262-76, 2012. PMCID:PMC3255917

Gonzalez-Hernandez, M. J., Swanson, M. D., Contreras-Galindo, R., Cookinham, S., King, S. R., Noel, R. J. Jr., Kaplan, M. H., and Markovitz, D. M. Expression of Human Endogenous Retrovirus Type-K (HML-2) is activated by the Tat protein of HIV-1. J. Virol. (epub ahead of print May 16, 2012). PMCID: PMC3421662. .

Saha, A. K., Kappes, F., Mundade, A., Deutzmann, A., Rosmarin, D., Legendre, M., Chatain, N., Al-Obaidi, Z., Adams, B. S., Ploegh, H., Ferrando-May, E., Mor-Vaknin, N.*,  and Markovitz, D. M.* Intercellular trafficking of the nuclear oncoprotein DEK. Proc. Natl. Acad. Sci., USA. 2013; 110(17):6847-52. PMC Journal – In Progress.

Contreras-Galindo, R., Kaplan, M.H., He, S., Contreras-Galindo, A.C., Gonzalez-Hernandez, M.J., Kappes, F., Dube, D., Chan, S.M., Robinson, D., Meng, F., Dai, M., Gitlin, S.D., Chinnaiyan, A.M., Omenn, G.S.  and Markovitz, D.M. HIV infection reveals wide-spread expansion of novel centromeric human endogenous retroviruses. Genome Res. (In Press) PMC Journal – In Progress.