Richard Sutton, MD/PhD
Research & Publications
Our laboratory is focused on the study of human immunodeficiency virus type I (HIV) replication and the development of small animal models of HIV. For example, mice are not susceptible to HIV due a profound block in HIV assembly and release from cells. We are exploring the nature of this block and are conducting genetic screens and biochemical assays to identify human genes that may be able to overcome this deficiency. Our work has zeroed in on host factor Crm1 and viral regulatory gene Rev; we have established a high throughput, cell-free assay in order to identify inhibitors of Rev function.
We also utilize replication-defective HIV as a vector to transduce non-dividing cells for gene therapeutic purposes and are developing novel methods of vector production. These vectors are used to investigate other viruses (for example, cellular binding and entry requirements of SARS-CoV-2, Ebola, and Western Equine Encephalitis) and to explore fundamental questions in molecular biology, such as high throughput identification of DNA elements that serve as transcriptional activators in various cell types, including human embryonic stem cells.
We are now funded through NIAID to use advanced molecular biology methods to identify both cis-acting DNA sequences and trans-acting protein factors that modulate CCR5 gene expression in primary human T cells and macrophages. CCR5 is a key co-receptor for many HIV isolates and eliminating CCR5 is central to the HIV cure effort. We have also been collaborating with investigators in Uganda to continue our studies of HIV+ elite controllers.
In collaboration with Dr. Priti Kumar, also of the ID section, we are funded by the NIH to examine the possibility of using adenoviral-vectored anti-HIV broadly neutralizing antibodies to counteract HIV, both as prophylaxis and as therapy, exploring their use in humanized murine models. In a somewhat related project we have constructed specialized adenovirus vectors in order to knock out the CCR5 gene in human progenitor cells, in vitro and in vivo.
Most recently, we have pivoted to COVID-19, and have been developing novel assays that quantify the functionality of the humoral immune response, after both natural infection and immunization. We recently published the development of a novel cell fusion assay to quantify the interaction between SARS-CoV-2 spike and hACE2, and we have a large, ongoing study to examine the humoral immune response after SARS-CoV-2 vaccination in US veterans.
Specialized Terms: HIV replication and the development of small animal models of HIV; HIV vectors; HIV replication and gene transfer into non-dividing cells, COVID-19, SARS-CoV-2.
HIV; Molecular Biology; Severe acute respiratory syndrome-related coronavirus; Infectious Disease Medicine
Public Health Interests
- Identification and characterization of HIV positive Ethiopian elite controllers in both Africa and IsraelKiros Y, Elinav H, Gebreyesus A, Gebremeskel H, Azar J, Chemtob D, Abreha H, Elbirt D, Shahar E, Chowers M, Turner D, Grossman Z, Haile A, Sutton R, Maayan S, Wolday D. Identification and characterization of HIV positive Ethiopian elite controllers in both Africa and Israel HIV Medicine 2018, 20: 33-37. PMID: 30318718, PMCID: PMC6510948, DOI: 10.1111/hiv.12680.
- Cell-Intrinsic ImmunityElinav H, Sutton R. Cell-Intrinsic Immunity 2018, 231-240. DOI: 10.1007/978-1-4939-7101-5_270.
- Cell-Intrinsic ImmunityElinav H, Sutton R. Cell-Intrinsic Immunity 2014, 1-11. DOI: 10.1007/978-1-4614-9610-6_270-1.
- What does the future hold for viral gene therapy?Sutton R. What does the future hold for viral gene therapy? Future Virology 2007, 2: 543-547. DOI: 10.2217/17460722.214.171.1243.
- Targeting proteinprotein interactions for HIV therapeuticsRice A, Sutton R. Targeting proteinprotein interactions for HIV therapeutics HIV Therapy 2007, 1: 369-385. DOI: 10.2217/17469600.1.4.369.
- Corrigendum to “Isolation and characterization of mouse–human microcell hybrid cell clones permissive for infectious HIV particle release” [Virology 362 (2007) 283–293]Coskun A, van Maanen M, Janka D, Stockton D, Stankiewicz P, Yatsenko S, Sutton R. Corrigendum to “Isolation and characterization of mouse–human microcell hybrid cell clones permissive for infectious HIV particle release” [Virology 362 (2007) 283–293] Virology 2007, 365: 473. DOI: 10.1016/j.virol.2007.06.003.
- HIV-based vectors for therapeutic angiogenesis in a rabbit model of hindlimb ischemiaConklin L, LeMaire S, Coselli J, McAninch R, Sutton R. HIV-based vectors for therapeutic angiogenesis in a rabbit model of hindlimb ischemia Journal Of Surgical Research 2003, 114: 284. DOI: 10.1016/j.jss.2003.08.045.
- Detection of Replication-Competent Lentiviral ParticlesSegall H, Sutton R. Detection of Replication-Competent Lentiviral Particles 2003, 87-94. DOI: 10.1385/1-59259-393-3:87.
- Monocyte/Macrophages and Dendritic CellsSegall H, Sutton R. Monocyte/Macrophages and Dendritic Cells 2003, 107-116. DOI: 10.1385/1-59259-393-3:107.
- Systematic Determination of the Packaging Limit of Lentiviral VectorsKumar M, Keller B, Makalou N, Sutton R. Systematic Determination of the Packaging Limit of Lentiviral Vectors Human Gene Therapy 2001, 12: 1893-1905. PMID: 11589831, DOI: 10.1089/104303401753153947.
- Transduction of Human PBMC-Derived Dendritic Cells and Macrophages by an HIV-1-Based Lentiviral Vector SystemSchroers R, Sinha I, Segall H, Schmidt-Wolf I, Rooney C, Brenner M, Sutton R, Chen S. Transduction of Human PBMC-Derived Dendritic Cells and Macrophages by an HIV-1-Based Lentiviral Vector System Molecular Therapy 2000, 1: 171-179. PMID: 10933928, DOI: 10.1006/mthe.2000.0027.
- Transduction of human progenitor hematopoietic stem cells by human immunodeficiency virus type 1-based vectors is cell cycle dependent.Sutton R, Reitsma M, Uchida N, Brown P. Transduction of human progenitor hematopoietic stem cells by human immunodeficiency virus type 1-based vectors is cell cycle dependent. Journal Of Virology 1999, 73: 3649-60. PMID: 10196257, PMCID: PMC104140, DOI: 10.1128/jvi.73.5.3649-3660.1999.
- HIV, but not murine leukemia virus, vectors mediate high efficiency gene transfer into freshly isolated G0/G1 human hematopoietic stem cellsUchida N, Sutton R, Friera A, He D, Reitsma M, Chang W, Veres G, Scollay R, Weissman I. HIV, but not murine leukemia virus, vectors mediate high efficiency gene transfer into freshly isolated G0/G1 human hematopoietic stem cells Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 11939-11944. PMID: 9751769, PMCID: PMC21744, DOI: 10.1073/pnas.95.20.11939.
- Human immunodeficiency virus type 1 vectors efficiently transduce human hematopoietic stem cells.Sutton R, Wu H, Rigg R, Böhnlein E, Brown P. Human immunodeficiency virus type 1 vectors efficiently transduce human hematopoietic stem cells. Journal Of Virology 1998, 72: 5781-8. PMID: 9621037, PMCID: PMC110379, DOI: 10.1128/jvi.72.7.5781-5788.1998.
- Identification of a major co-receptor for primary isolates of HIV-1Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Marzio P, Marmon S, Sutton R, Hill C, Davis C, Peiper S, Schall T, Littman D, Landau N. Identification of a major co-receptor for primary isolates of HIV-1 Nature 1996, 381: 661-666. PMID: 8649511, DOI: 10.1038/381661a0.
|Diseases of the Nervous System; HIV/AIDS; Infectious Diseases; COVID-19 Inpatient; COVID-19 Outpatient||HIV Associated Reservoirs and Comorbidities (The HARC Plus Study)|
|HIV/AIDS||Mechanisms of HIV latency|
|Addictive Behaviors; HIV/AIDS; Infectious Diseases||Impact of HIV Infection on Immunologic, Transcriptomic, and Metabolomic Signatures|