The research interests of Eric M. Poeschla, M.D., are in the molecular pathogenesis of HIV/AIDS, host cell viral dependency factors, innate immunity to viruses and viral vector-based human gene therapy.
The basic HIV research of Dr. Poeschla and his colleagues concentrates on the molecular biology and cell biology of viral replication, including host cell dependency factors, antiviral restriction factors, integration and genome encapsidation.
His group contributed foundational work on the HIV-1 integration cofactor LEDGF (e.g., Science 314:461-4, 2006; Nature Methods 11:1287-9, 2005) and continues to be very interested in cellular protein roles in the post-entry events that culminate in HIV-1 integration.
Dr. Poeschla's team focuses on HIV-1, but the primate-nonprimate lentiviral/host comparison and the animal-human interface has been a theme since they constructed the first feline immunodeficiency virus (FIV) vectors (Nature Medicine 4:354-7, 1998).
Dr. Poeschla and his colleagues recently developed new germline transgenesis methods in order to enable genetic modification of an AIDS lentivirus and AIDS-susceptible species for the first time (e.g., Nature Methods 85:3570-83, 2011; see also National Geographic, February 2012, NEXT section).
They are currently studying the introduction of protective antiviral genes of interest for human gene therapy of HIV-1 disease in this model system; applications to non-infectious disease are also foreseen.
In related translational work, his group uses lentiviral vectors that are based on both HIV-1 and FIV to transduce terminally differentiated tissues in the eye and brain; they have developed a candidate glaucoma gene therapy (e.g., Molecular Therapy 18:491-501, 2010).
For more information, visit Dr. Poeschla's lab site.
Significance to patient care
HIV-1 infection, which was almost uniformly fatal not long ago, is now eminently treatable with long-term combination antiviral therapy. Nevertheless, we face many problems, such as continued body-wide inflammation, metabolic syndromes and accelerated aging phenomena in treated patients, drug toxicities, drug resistance, expense, lack of access in countries where the vast majority of infections occur, and most importantly, the lack of a vaccine on the horizon.
Drugs that target the post-entry virus as it makes its way to the chromosome of the target cell are presently limited to reverse transcriptase and integrase catalysis inhibitors, but these nucleic acid catalysis reactions are only two of many complex post-entry transformations that virion contents must undergo. New strategies that target other steps or viral interaction with host cell proteins such as LEDGF have promise.
Harnessing the power of restriction factors is equally on the field's radar. This will depend upon deciphering how viruses evade such defenses.
The transgenic modeling project is designed to advance basic understanding of replication, pathogenesis, and antiviral immunity at the cellular and systemic levels in vivo and to model gene therapies for HIV/AIDS. Applications to other diseases are feasible.
Glaucoma remains a leading cause of irreversible blindness. The Gene Therapy in the Eye project, in which Dr. Poeschla collaborates with the Department of Ophthalmology, is aimed at devising novel treatments for this and other chronic or malignant eye diseases.