fEATURED Research associate: Mark Stenglein

Mark Stenglein

Mark Stenglein received his PhD from the University of Minnesota in August 2009.  Mark’s doctoral research was conducted under the mentorship of Dr. Reuben Harris, a faculty member in the Department of Biochemistry, Molecular Biology, and Biophysics, the Institute for Molecular Virology, and the Center for Genome Engineering.

Prior to his graduate studies, Mark received a B.A. from Washington University in Saint Louis in 1997, studying Mathematics and French.  Mark then worked for seven years for an aerospace engineering company.  Deciding that he wanted to shift his career to one focusing on the part of his job that he enjoyed the most, namely problem solving, Mark decided to begin a career in scientific research, and entered graduate school in 2004.  Mark was drawn to the Harris lab because of its fascinating research topics and its enthusiastic and energetic approach to science.

In the Harris lab, Mark’s doctoral research has focused on a family of human proteins named the APOBEC3s.  These proteins have the ability to deaminate (i.e. to chemically modify) DNA.  Like the software programs that run a computer, a cell’s DNA provides its operating instructions.  Consequently, cells go to great lengths to ensure that their DNA remains safe and undamaged.  At the same time, cells must prevent foreign DNA from persisting within them, or risk having their operations hijacked (like a software virus can hijack a computer.)  So cells must carefully protect their own DNA, but somehow eliminate foreign DNA, and Mark’s research has helped show how APOBEC3 proteins help fulfill this double imperative.

Previously, it was known that APOBEC3 proteins attack (deaminate) and neutralize the DNA of viruses such as HIV.  Mark’s research has shown that it is not just viral DNA that is subject to destruction by APOBEC3s, but also mobile and foreign DNA in general.

Mark first showed that APOBEC3 proteins prevent the replication of mobile DNA elements called L1s.  L1s are in principle like viruses, but unlike viruses, which move from cell to cell, L1s move within cells.  L1s are thought to be the only mobile DNA that is active in humans, and L1 mobilization can lead to diseases such as cancer.  Mark demonstrated that APOBEC3 proteins limit L1 mobility (Stenglein and Harris (2006) JBC).

The second major finding of Mark’s thesis was the discovery that APOBEC3 proteins attack and destabilize any foreign intracellular DNA, not just that of viruses and mobile DNA elements.  It was previously known that foreign DNA within cells triggered a strong immune alarm, but it was not known how cells responded to this alarm to clear the foreign DNA.  It appears that APOBEC3 proteins may form a principal part of this response (Stenglein et al (2009) In Review).  Understanding this potent anti-DNA defense system has potentially important implications for genetic engineering and gene therapy.  Both of these techniques rely on the purposeful introduction of DNA into cells, a process that may be thwarted by APOBEC3 proteins. 

Thus, Mark’s research has demonstrated that, analogous to antiviral computer software, APOBEC3 proteins simultaneously protect the cell’s own DNA and destroy dangerous invasive DNA.

Mark is continuing his research in the Harris lab as a postdoctoral researcher until the end of 2009, when he will move to San Francisco to perform postdoctoral research in the labs of Drs. Don Ganem and Joseph DeRisi.  In recognition of his achievements during graduate school, Mark has received a 3M Science and Technology Graduate Fellowship, a Cancer Biology Training Grant Predoctoral Fellowship, the Dr. Marvin and Hadassah Bacaner Research Award, and the Fredrick J. Bollum Award. 

publications:

  • Refsland EW*, Stenglein MD*, and Harris RS (2009) Quantitative Analyses of APOBEC3 mRNA Levels in Human Lymphocytes and Tissues. In preparation. (* Equal Contributions).

  • Stenglein MD, and Harris RS (2009) Foreign DNA Restriction by APOBEC3A. In Review.

  • Stenglein MD, Schumacher AJ, LaRue RS, and Harris RS (2009) Host factors that restrict retrovirus replication.  In Viral Genome Replication, C. Cameron, M. Götte, and K. Raney, eds.  Springer.  297-336.

  • Stenglein MD, Mastsuo H, and Harris RS (2008) Two regions within the amino-terminal half of APOBEC3G cooperate to determine cytoplasmic localization. J. Virol. 82: 9591-9.

  • Jónsson SR, LaRue RS, Stenglein MD, Fahrenkrug S, Andrésdóttir A, and Harris RS (2007) The restriction of zoonotic PERV transmission by human APOBEC3G. PLoS One 2: e893.

  • Stenglein MD, and Harris RS (2006) APOBEC3B and -3F inhibit L1 retrotransposition by a DNA deamination-independent mechanism.  J. Biol. Chem. 281: 16837-41.

  • Jónsson SR, Haché G, Stenglein MD, Fahrenkrug SC, Andresdottir V, and Harris RS (2006) Evolutionarily conserved and non-conserved retrovirus restriction activities of artiodactyl APOBEC3F proteins.  Nucleic Acids Res. 34: 5683-94