Dr Sarah Palmer
PhD
Associate Professor
The Westmead Institute for Medical Research
| Telephone | +61 2 862 73620 |
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| Curriculum vitae | Curriculum vitae |
Biographical details
Dr. Sarah Palmer is the Deputy Director of the Centre for Virus Research at The Westmead Institute for Medical Research and Associate Professor in the Faculty of Medicine at the University of Sydney.
Prior to taking up this position in early 2013, she was a Senior Researcher at the Swedish Institute for Communicable Disease Control and Karolinska Institutet, in Stockholm, Sweden from 2008 to 2012. From 2000 to 2008, she headed the Virology Core Facility of the HIV Drug Resistance Program, National Cancer Institute, US National Institutes of Health, where she led efforts to develop and perfect highly-sensitive assays such as the single-copy assay and single-cell sequencing assay which provide new insights into HIV pathogenesis and persistence during long-term suppressive therapy.
Dr. Palmer has her Ph.D. in Medical Sciences (Virology) from the Karolinksa Institutet, and conducted her post-doctoral studies at the Center for AIDS Research, Stanford University Medical School.
Research interests
HIV Pathogenesis and HIV Reservoirs: Our group’s principal areas of research interest focus on molecular and medical virology and the application of innovative techniques and assays which provide new insights into disease pathogenesis and treatment, especially for HIV. Our current work focuses on understanding the genetic characteristics and dynamics of persistent HIV across a range of tissues and cells to guide and assess treatment interventions designed to reduce persistent HIV reservoirs and inform HIV eradication strategies.
Teaching and supervision
COURSES TAUGHT
Infection: Causes and Defense: preclinical lectures for medical students
Antiviral Therapy Seminars: preclinical seminars for medical students
New Insights into the Host-HIV Relationship: graduate student lecture series
Virology and Antiviral Therapy: undergraduate students in biomedical technology
Current research students
| Project title | Research student |
|---|---|
| Identifying and targeting HIV persistence in T cell subsets during prolonged antiretroviral therapy. | Eunok LEE |
Current projects
DARE: Delaney AIDS Research Enterprise to find a cure: Our research group is a part of an ongoing international initiative concerned with HIV eradication strategies funded by the US NIH
Characterizing Latent HIV-1 Reservoirs: Our research group is conducting an in-depth analysis of peripheral blood and tissue samples from patients to provide an unprecedented systematic survey of three important factors which influence the magnitude and nature of the HIV reservoir in patients on effective therapy: treatment initiation (during acute versus chronic infection); the pool of follicular dendritic cell-associated virions in lymphoid follicles; and host genetics (CCR-5 Δ32 heterozygosity).
Genetic analysis of unspliced HIV RNA produced during HDAC inhibitor therapy: Despite advances in the treatment of HIV-infected patients, including the complete or near-complete inhibition of viral replication with standard therapies, replication-competent HIV persists indefinitely in all infected individuals. This latent form persists even in persons under effective therapy and can actively and life-threateningly rebound if therapy stops or is taken incorrectly. One promising approach to eradicate HIV and cure infected individuals is to reactivate and target this latent HIV for elimination. During recent clinical trials, latent HIV was reactivated in patients who while on effective therapy were also treated with compounds called histone deacetylaseinhibitors. In conducting this study we are investigating the genetic makeup of this reactivated HIV to determine which cells and tissue compartments are producing this HIV. We anticipate this study will reveal which cells are most prone to HIV reactivation by histone deacetylaseinhibitor therapy. In addition, this study will provide evidence that this reactivated HIV is an important prognostic marker for the latent form of HIV found in cells, an important step in current treatment strategies aimed at eradicating and curing HIV infection.
Longitudinal assessment of the relationship between immune activation and HIV persistence: T cell proliferation, differentiation and activation have poorly defined effects on the latent HIV reservoir during ART. We recently found that the most consistent association correlate of reservoir size is the frequency of memory CD4+ T cells expressing HLA-DR, which is upregulated upon activation. In conducting this project we are measuring the levels of cellular activation markers over time in subjects who have been on ART for 15 years, and determining how these markers predict changes of infection frequency, genetic makeup, and replication competency of HIV in memory T cells. Specifically, we will determine if the inducible reservoir is enriched in cells expressing markers of activation.
The Impact of HBV coinfection on the HIV Reservoir:Approximately 10% of HIV-infected individuals worldwide are co-infected with HBV and co-infected individuals have a 17-fold greater risk of developing liver cancer compared to HBV-mono-infected individuals or 8.4-fold greater risk compared to HIV-mono-infected individuals. Despite the high mortality rates of these co-infections even for patients on therapy, there have been few studies on HBV and HIV co-infections. While studies have shown that HIV exacerbates the natural course of disease progression of HBV by unknown mechanisms, the impact of HBV infection on the natural course of HIV infection is unclear. This study will focus on HIV-HBV co-infections to elucidate whether HBV co-infection has any impact on the HIV replication and reservoir formation.
Delineating the role of turnover rates and T cell activation in maintaining the latent HIV reservoir during effective antiretroviral therapy: This study of cellular mechanisms will investigate whether cellular half-lives affect the level of replication-competent proviruses. Recently, our collaborators at the University of California, San Francisco, Drs. Peter Hunt and Charline Bacchus-Souffan, used established labelling techniques to measure CD4+ T cell turnover based on in vivo incorporation of deuterium into genomic DNA in sort purified HLA-DR negative CD4 T naïve (TN), stem cell memory (TSCM), central memory (TCM), transitional memory (TTM), effector memory (TEM), and effector (TEMRA) cells, after oral administration of deuterated water. In conducting this study they found that the half-life of CD4+ T cell subpopulations decreased significantly with increasing maturation status (p< 0.04). A shorter cellular half-life was associated with higher levels of integrated HIV-1 DNA and cell-associated RNA content (r=0.53, p< 0.0001), with enrichment of virus in shorter lived subpopulations, e.g., TEM, TTM, and TCM (p< 0.019). What remains unclear from this work is whether the virus that is enriched in these shorter-lived populations is replication incompetent and can be “ignored” or whether these more rapidly turning over cell populations harbor replication competent virus that needs to be targeted. In collaboration with Drs. Hunt and Bacchus-Souffan, we will sequence the intact proviruses in sorted memory T cells with known turnover rates and number of HIV-1 integration sites.
In the media
Sheridon, Kate. “HIV Cure: New way to find hidden cells brings scientists one step closer.” 19 Oct. 2017, www.newsweek.com/hiv-cure-new-way-find-hidden-cells-brings-scientists-closer-688532
Selected grants
2018
- Genetic characterization of the HIV-1 reservoir after Vacc-4x and romidepsin therapy; Palmer S; National Institutes of Health (USA)/Research Support.
- Defining Persistent Reservoirs of HIV-1 after Vacc-4x and Romidepsin Therapy; Palmer S; Australian Centre for HIV and Hepatitis Virology Research (ACH2)/HIV and Hepatitis C Virology and Immunology Research Grants.
2016
- DARE: Delaney AIDS Research Enterprise to cure HIV; Palmer S; National Institutes of Health (USA)/Research Grant.
- 1) NIMH-related studies (use of CSF) = NeuroHIV Cure Consortium (Protocols: RV254, RV397, RV398) 2) DAIDS-sponsored studies (use of plasma) = RV397 & RV398; Palmer S; US Army Medical Research Acquisition Group/Research Grant.
- Defining the Interaction of HIV with the Interferon System in Initial Mucosal Infection; Cunningham A, Harman A, Palmer S, Nasr N, Diefenbach R, Sandgren K; National Health and Medical Research Council (NHMRC)/Project Grants.
- Long term persistence of HIV in the liver and the clinical impact on HIV-HBV co-infection; Lewin S, Churchill M, Palmer S, Avihingsanon A; National Health and Medical Research Council (NHMRC)/Project Grants.
2015
- The Role of Dendritic Cells in Sexual Transmission of HIV and Viral Reservoir Formation; Harman A, Cunningham A, Palmer S, Kim M, Nasr N; National Health and Medical Research Council (NHMRC)/Project Grants.
2014
- Genetic analysis of unspliced HIV RNA produced during HDAC inhibitor therapy; Palmer S, Lewin S, Rasmussen T; National Institutes of Health (USA)/Research Support.
- Understanding the role of treatment timing cells and human genetics to explain why HIV drugs do not cure HIV.; Palmer S, Hecht F, Cunningham A, Churchill M, Cameron P; National Health and Medical Research Council (NHMRC)/Project Grants.
2013
- DARE: Delaney AIDS Research Enterprise to find a cure; Palmer S; National Institutes of Health (USA)/Research Support.
Selected publications
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