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David M. Rekosh

David M. Rekosh

Professor, Microbiology, Immunology, and Cancer Biology

Primary Location
PO Box 800734
Pinn Hall 7088
Primary Phone Number
434.982.1599
Email
[email protected]

Bio & Overview

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. HIV Rev 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 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.

Academic Information

Department
Microbiology, Immunology, and Cancer Biology
Academic Title
Professor

Primary Education

  • AB, Chemistry/Biological Science, Cornell Universitynull
  • PhD, Microbiology, Massachusetts Institute of Technologynull
  • Postdoc, Molecular Virology, Imperial Cancer Research Fundnull
  • Postdoc, Virology, National Institute for Medical Research null

Other Appointments

  • Professor, Microbiology, Immunology, and Cancer Biology
  • Professor, BMBG
  • Professor, MOMD

Other Affiliations

  • Member, Cancer Cell Signaling Program
  • BIMS
  • Professor, BIMS
  • Director, Myles H. Thaler Center

Research Interests

Human Immunodeficiency Virus Gene Expression; Human Endogenous Viruses; SARS-CoV-2 Protein Trafficking; Post-transcriptional Gene Regulation

Research Disciplines

  • Biochemistry
  • Bioinformatics and Genomics
  • Biophysics
  • Biophysics & Structural Biology
  • Biotechnology
  • Cancer Biology
  • Epigenetics
  • Genetics
  • Immunology
  • Infectious Diseases/Biodefense
  • Microbiology
  • Molecular Biology
  • Structural Biology
  • Translational Science

Research Opportunities

  • Biochemistry
  • Bioinformatics & Genomics
  • Biophysics & Structural Biology
  • Biotechnology
  • Cancer Biology
  • Epigenetics
  • Genetics
  • Immunology
  • Infectious Diseases
  • Microbiology
  • Molecular Biology

PhD Programs

  • Biochemistry & Molecular Genetics
  • Microbiology

Selected Publications

2024

Jackson, P. E. H., Dzhivhuho, G., Huang, J., Hammarskjold, M. -L., & Rekosh, D. (2024). Measurement of HIV Rev-Rev Response Element Functional Activity.. Methods in molecular biology (Clifton, N.J.), 2807, 175-194. doi:10.1007/978-1-0716-3862-0_13

2023

Jackson, P. E. H., Holsey, J., Turse, L., Hammarskjold, M. -L., & Rekosh, D. (2023). Rev-Rev Response Element Activity Selection Bias at the Human Immunodeficiency Virus Transmission Bottleneck. OPEN FORUM INFECTIOUS DISEASES, 10(10). doi:10.1093/ofid/ofad486

Jackson, P. E. H., Holsey, J., Turse, L., Marie-Louise, H., & Rekosh, D. (2023). Rev-Rev Response Element Activity Selection Bias at the HIV Transmission Bottleneck.. bioRxiv. doi:10.1101/2023.04.05.535732

2022

Dzhivhuho, G., Holsey, J., Honeycutt, E., O'Farrell, H., Rekosh, D., Hammarskjold, M. -L., & Jackson, P. E. H. (2022). HIV-1 Rev-RRE functional activity in primary isolates is highly dependent on minimal context-dependent changes in Rev. SCIENTIFIC REPORTS, 12(1). doi:10.1038/s41598-022-21714-2

2020

Grabski, D. F., Broseus, L., Kumari, B., Rekosh, D., Hammarskjold, M. -L., & Ritchie, W. (2021). Intron retention and its impact on gene expression and protein diversity: A review and a practical guide. WILEY INTERDISCIPLINARY REVIEWS-RNA, 12(1). doi:10.1002/wrna.1631

Grabski, D. F., Ratan, A., Gray, L. R., Bekiranov, S., Rekosh, D., Hammarskjold, M. -L., & Rasmussen, S. K. (2021). Upregulation of human endogenous retrovirus-K (HML-2) mRNAs in hepatoblastoma: Identification of potential new immunotherapeutic targets and biomarkers. JOURNAL OF PEDIATRIC SURGERY, 56(2), 286-292. doi:10.1016/j.jpedsurg.2020.05.022

Mavhandu, L. G., Cheng, H., Bor, Y. -C., Tebit, D. M., Hammarskjold, M. -L., Rekosh, D., & Bessong, P. O. (2020). Development of a pseudovirus assay and evaluation to screen natural products for inhibition of HIV-1 subtype C reverse transcriptase. JOURNAL OF ETHNOPHARMACOLOGY, 258. doi:10.1016/j.jep.2020.112931

Jackson, K. N., Kahler, D. M., Kucharska, I., Rekosh, D., Hammarskjold, M. -L., & Smith, J. A. (2020). Inactivation of MS2 Bacteriophage and Adenovirus with Silver and Copper in Solution and Embedded in Ceramic Water Filters. JOURNAL OF ENVIRONMENTAL ENGINEERING, 146(3). doi:10.1061/(ASCE)EE.1943-7870.0001634

Jackson, P. E. H., Dzhivhuho, G., Rekosh, D., & Hammarskjold, M. -L. (2020). Sequence and Functional Variation in the HIV-1 Rev Regulatory Axis. CURRENT HIV RESEARCH, 18(2), 85-98. doi:10.2174/1570162X18666200106112842

2019

Gray, L. R., Jackson, R. E., Jackson, P. E. H., Bekiranov, S., Rekosh, D., & Hammarskjold, M. -L. (2019). HIV-1 Rev interacts with HERV-K RcREs present in the human genome and promotes export of unspliced HERV-K proviral RNA. RETROVIROLOGY, 16(1). doi:10.1186/s12977-019-0505-y

Sherpa, C., Jackson, P. E. H., Gray, L. R., Anastos, K., Le Grice, S. F. J., Hammarskjold, M. -L., & Rekosh, D. (2019). Evolution of the HIV-1 Rev Response Element during Natural Infection Reveals Nucleotide Changes That Correlate with Altered Structure and Increased Activity over Time. JOURNAL OF VIROLOGY, 93(11). doi:10.1128/JVI.02102-18

Jackson, P. E. H., Huang, J., Sharma, M., Rasmussen, S. K., Hammarskjold, M. -L., & Rekosh, D. (2019). A novel retroviral vector system to analyze expression from mRNA with retained introns using fluorescent proteins and flow cytometry. SCIENTIFIC REPORTS, 9. doi:10.1038/s41598-019-42914-3

Matume, N. D., Tebit, D. M., Gray, L. R., Turner, S. D., Rekosh, D., Bessong, P. O., & Hammarskjold, M. -L. (2019). Characterization of APOBEC3 variation in a population of HIV-1 infected individuals in northern South Africa. BMC MEDICAL GENETICS, 20. doi:10.1186/s12881-018-0740-4

2018

Rekosh, D., & Hammarskjold, M. -L. (2018). Intron retention in viruses and cellular genes: Detention, border controls and passports. WILEY INTERDISCIPLINARY REVIEWS-RNA, 9(3). doi:10.1002/wrna.1470

Matume, N. D., Tebit, D. M., Gray, L. R., Hammarskjold, M. -L., Rekosh, D., & Bessong, P. O. (2018). Next generation sequencing reveals a high frequency of CXCR4 utilizing viruses in HIV-1 chronically infected drug experienced individuals in South Africa. JOURNAL OF CLINICAL VIROLOGY, 103, 81-87. doi:10.1016/j.jcv.2018.02.008

2017

Hammarskjold, M. -L., & Rekosh, D. (2017). SR proteins: To shuttle or not to shuttle, that is the question. JOURNAL OF CELL BIOLOGY, 216(7), 1875-1877. doi:10.1083/jcb.201705009

2016

Li, Y., Bor, Y. -C., Fitzgerald, M. P., Lee, K. S., Rekosh, D., & Hammarskjold, M. -L. (2016). An NXF1 mRNA with a retained intron is expressed in hippocampal and neocortical neurons and is translated into a protein that functions as an Nxf1 cofactor. MOLECULAR BIOLOGY OF THE CELL, 27(24), 3903-3912. doi:10.1091/mbc.E16-07-0515

Wynn, J. E., Zhang, W., Tebit, D. M., Gray, L. R., Hammarskjold, M. -L., Rekosh, D., & Santos, W. L. (2016). Effect of intercalator and Lewis acid-base branched peptide complex formation: boosting affinity towards HIV-1 RRE RNA. MEDCHEMCOMM, 7(7), 1436-1440. doi:10.1039/c6md00171h

Jackson, P. E., Tebit, D. M., Rekosh, D., & Hammarskjold, M. -L. (2016). Rev-RRE Functional Activity Differs Substantially Among Primary HIV-1 Isolates. AIDS RESEARCH AND HUMAN RETROVIRUSES, 32(9), 923-934. doi:10.1089/aid.2016.0047

Wynn, J. E., Zhang, W., Tebit, D. M., Gray, L. R., Hammarskjold, M. -L., Rekosh, D., & Santos, W. L. (2016). Characterization and in vitro activity of a branched peptide boronic acid that interacts with HIV-1 RRE RNA. BIOORGANIC & MEDICINAL CHEMISTRY, 24(17), 3947-3952. doi:10.1016/j.bmc.2016.04.009

2015

Sherpa, C., Rausch, J. W., Le Grice, S. F. J., Hammarskjold, M. -L., & Rekosh, D. (2015). The HIV-1 Rev response element (RRE) adopts alternative conformations that promote different rates of virus replication. NUCLEIC ACIDS RESEARCH, 43(9), 4676-4686. doi:10.1093/nar/gkv313

Wang, B., Rekosh, D., & Hammarskjold, M. -L. (2015). Evolutionary conservation of a molecular machinery for export and expression of mRNAs with retained introns. RNA, 21(3), 426-437. doi:10.1261/rna.048520.114

2013

Sloan, E. A., Kearney, M. F., Gray, L. R., Anastos, K., Daar, E. S., Margolick, J., . . . Rekosh, D. (2013). Limited Nucleotide Changes in the Rev Response Element (RRE) during HIV-1 Infection Alter Overall Rev-RRE Activity and Rev Multimerization. JOURNAL OF VIROLOGY, 87(20), 11173-11186. doi:10.1128/JVI.01392-13

Murgai, M., Thomas, J., Cherepanova, O., Delviks-Frankenberry, K., Deeble, P., Pathak, V. K., . . . Owens, G. (2013). Xenotropic MLV envelope proteins induce tumor cells to secrete factors that promote the formation of immature blood vessels. RETROVIROLOGY, 10. doi:10.1186/1742-4690-10-34

2011

Iweriebor, B. C., Mavhandu, L. G., Masebe, T., Rekosh, D., Hammarskjold, M. -L., Mphahlele, J. M., & Bessong, P. O. (2012). Molecular epidemiology of HIV in two highly endemic areas of northeastern South Africa. ARCHIVES OF VIROLOGY, 157(3), 455-465. doi:10.1007/s00705-011-1180-z

Coyle, J. H., Bor, Y. -C., Rekosh, D., & Hammarskjold, M. -L. (2011). The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway. RNA, 17(7), 1344-1356. doi:10.1261/rna.2616111

Hammarskjold, M. -L., & Rekosh, D. (2011). A Long-Awaited Structure Is Rev-ealed. VIRUSES-BASEL, 3(5), 484-492. doi:10.3390/v3050484

Shuck-Lee, D., Chang, H., Sloan, E. A., Hammarskjold, M. -L., & Rekosh, D. (2011). Single-Nucleotide Changes in the HIV Rev-Response Element Mediate Resistance to Compounds That Inhibit Rev Function. JOURNAL OF VIROLOGY, 85(8), 3940-3949. doi:10.1128/JVI.02683-10