Dr. David Markovitz
University of Michigan – Division of Infectious Diseases
Professional Summary
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.
The Markovitz laboratory 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 worldwide. 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, as well as to the American Clinical and Climatological Association.
In addition to his research, Dr. Markovitz is a consultant on the Infectious Diseases service at the Veterans Hospital and rounds on general Internal Medicine wards at the University of Michigan Hospital.
The Markovitz laboratory focuses on understanding how human cellular factors control the replication of viruses, retroviruses in particular. These studies are performed both to understand the biology of viruses 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. This line of investigation has also led to work on the genetics of one of the least-explored regions of the genome, the centromere, leading further to studies of the pathogenesis of scleroderma.
A second project deals with the biochemically distinct DEK protein, which is involved in cancer causation, hematopoiesis, and the pathogenesis of juvenile arthritis, and has a highly unusual life cycle.
Third, the laboratory is working with a molecularly engineered banana lectin that shows promise as a broad-spectrum antiviral agent and anti-cancer therapeutic.
Lastly, the Markovitz research group is studying the role of the intermediate filament protein vimentin in inflammation.
What are you currently pursuing concerning infectious diseases?
Lectins have the potential to be used as antiviral agents due to their ability to bind sugars, especially mannose, on the surface of multiple pathogenic viruses and thus block their ability to attach to cellular receptors. We demonstrated that a lectin from bananas, termed BanLec, is a potent inhibitor of HIV infection. However, BanLec as it is naturally derived from bananas is highly mitogenic, making it undesirable for use as either a systemic therapy or for blocking vaginal transmission of HIV. We overcame this problem by making a single amino acid mutation that totally disrupts mitogenicity while preserving broad-spectrum antiviral activity against HIV, hepatitis C virus, influenza, and all pathogenic coronaviruses, including SARS-CoV-2, SARS-CoV-1, and MERS-CoV. This compound, termed H84T BanLec because the histidine at position 84 has been changed to a threonine, has now been patented in the United States and China and in several countries in Europe.
What aspect of virus-cell interaction has drawn your research interest?
By uncovering how viruses usurp human cellular pathways for their own nefarious purposes, we have gained insight into cell biology relevant to cancer and autoimmunity. This approach is illustrated by our studies of the DEK protein, which we originally came to study when we discovered that it interacted with the transcriptional enhancer of HIV-2. DEK is a biochemically distinct protein that has been implicated in the pathogenesis of cancer and, in its pro-inflammatory role, in the pathogenesis of juvenile arthritis. We have detailed the complex life cycle of DEK, wherein it serves as a crucial chromatin factor, is secreted and acts as a chemotactic factor, and can then be taken back up by other cells in a bioactive manner wherein it corrects the chromatin and DNA repair defects seen in cells that do not contain DEK. We have proven at the genetic level that DEK is vital to inflammation and is key to neutrophil extracellular traps (NETs) and have developed an anti-DEK aptamer that has pronounced anti-inflammatory activity in a mouse model. Most recently, we have shown that DEK is a key factor in hematopoiesis.
Overview of the University of Michigan—Infectious Diseases Division
The Division of Infectious Diseases at Michigan Medicine was founded in 1967. Since that time, our division has grown to over 40 faculty members and has become nationally recognized for an exemplary record of patient care, research, and education and training.
Patient Care
We diagnose and treat patients for a multitude of infections including chronic bone and joint infections, soft tissue infections, endocarditis, opportunistic infections, complicated urinary tract infections, fungal infections, Clostridium difficile infection, and many others. In response to emerging and growing needs over the years, we have established several programs and clinics including the Fecal Microbiota Transplant Program(link is external), HIV/AIDS Treatment Program (link is external), Overseas Travel Clinic (link is external), and Transplant Infectious Diseases Service (link is external). Learn more.
Research
The Division of Infectious Diseases has a strong basic science and translational investigation program that includes virology, bacteriology, microbial diversity, mycology, and the intestinal microbiome. There is also a research component in our HIV/AIDS Treatment Program, Transplant Infectious Disease Service, and the Antimicrobial Stewardship Program. In the 2019 fiscal year, our division received over $12 million in federal, industry, and foundation funding to support our research activities. Learn more.
Education and Training
We have a long-standing Infectious Diseases Fellowship Training Program where over 95 Infectious Diseases specialists have completed their fellowship training, since our first graduates in 1970. View our Past Fellows. In addition, our faculty are actively involved in educating and training students within the Department of Internal Medicine, as well as teaching infectious diseases and microbiology courses in other departments at the University of Michigan including the Department of Ecology and Evolutionary Biology (link is external), Department of Epidemiology (link is external), Department of History (link is external), and the Department of Microbiology & Immunology. Learn more.