Rekosh, David M.
Professor, Microbiology, Immunology, and Cancer Biology
- AB, Chemistry/Biological Science, Cornell University
- PhD, Microbiology, Massachusetts Institute of Technology
- Postdoc, Molecular Virology, Imperial Cancer Research Fund
- Postdoc, Virology, National Institute for Medical Research
Biochemistry, Bioinformatics and Genomics, Biophysics, Biotechnology, Cancer Biology, Epigenetics, Genetics, Immunology, Infectious Diseases/Biodefense, Microbiology, Molecular Biology, Structural Biology, Translational Science
Human Immunodeficiency Virus Gene Expression; Human Endogenous Viruses; SARS-CoV-2 Protein Trafficking; Post-transcriptional Gene Regulation
Our research on viruses provides insight not only into the diseases they cause, but it also leads to the discovery of novel basic mechanisms that operate in eukaryotic cells. Over the years we have studied many different viruses and the cellular processes that they interact with. Most of our projects are in collaboration with Marie-Louise Hammarskjold.
The centerpiece of our HIV research is focused on the elucidation of the function of the HIV Rev protein. A primary function of this protein is to facilitate the nucleo-cytoplasmic export of HIV mRNAs that retain complete introns. mRNAs with retained introns are usually restricted by the cell from exiting the nucleus and since many HIV mRNAs have this property, Rev is essential for HIV replication.
Many details of Rev function remain unknown and our recent work focuses on some of these issues. In particular, we are studying how small variations in the sequence of Rev and the RRE can modulate HIV infection and replication, and the significance that this may have for pathogenesis and latency. We are also studying the cellular mechanisms that prevent RNA with retained introns from exiting the nucleus in the first place.
Human Endogenous Retroviruses (HERVs)
HERVs are transposable genomic elements that have integrated into the human germline over many millions of years. They comprise an estimated 8% of the human genome. HERV-Ks are the most recent HERVs to integrate and some are still capable of producing viral proteins. Novel HERV-K mRNA expression has been demonstrated in multiple cancers and it has also been shown to be regulated during embryogenesis.
We are interested in understanding the interaction of the HERV-K Rec protein with cellular genes, as Rec has been shown to bind to cellular mRNAs. Our research focuses on the possible role that HERV-K Rec might play in some human cancers and other instances of cellular gene regulation.
SARS-CoV-2 is the cause of COVID-19. Although most of its replication occurs in the cytoplasm of the infected cell, several of its proteins are known to enter the nucleus. We are presently elucidating the signals in the viral N protein that mediate both nuclear import and export. Elucidating the interactions of the N protein with host cell factors involved in nucleocytoplasmic trafficking, and a determination of how N perturbs host cell gene expression through its nuclear functions is likely to yield novel insights into how SARS-CoV-2 co-opts the cellular machinery towards its own ends. This could also lead to the identification of novel drug targets.
Cellular Post-transcriptional Gene Regulation
Many cellular genes express mRNA isoforms that retain introns. We have been studying the special mechanisms by which these RNAs are exported to the cytoplasm and have identified sequences that mediate the nucleocytoplasmic export and translation of mRNAs with retained introns. Our goal is to understand the role played by intron retention in the regulation of gene expression.