Samuel Weissman of the O’Doherty Lab won second place in this year's Regeneron Science Talent Search, the nation’s oldest and most prestigious science and math competition for high school seniors. The award includes $175,000 in prize money. Dr. O'Doherty met Sam through her son Liam. "Sam [a friend of Liam] started pestering me to volunteer in my lab several years ago. I was admittedly reluctant, but Sam soon proved useful. After learning to code in R, he developed methods to analyze longitudinal HIV sequences."
Sam is one of three co-first authors on a paper published in Nature Communications which studied the dynamics of the HIV reservoir by longitudinal proviral sequencing [https://www.nature.com/articles/s41467-019-08431-7.] This work suggests that the HIV reservoir is highly dynamic but this is masked by two opposing forces that contribute to HIV persistence. Both forces are generated by transcription leading to (1) HIV translation and reservoir clearance, or (2) aberrant splicing to downstream human exons that can lead to cell division. Sam plans to save this money for college (or perhaps make a down payment for a Ferrari 488). This coming year, Sam will work full-time in the O’Doherty lab.
- Link to article: Harriton H.S. senior wins prestigious science award for work on HIV
José Bauermeister, Presidential Professor of Nursing and Director of the CFAR Technologies to Reduce HIV Disparities Scientific Working Group, has developed an online tool designed to decrease sexual risk-taking and promote HIV/STI prevention behaviors among young gay, bisexual, and other men who have sex with men (YGBMSM), many of whom frequently meet their partners online.
- Link to article: To prevent HIV, start online
Dr. Drew Weissman, who has developed nucleoside-modified mRNA-lipid nanoparticle (LNP) as a novel platform for vaccines, showed that the vaccine and LNPs specifically induce high levels of T follicular helper cells (Tfh). Tfh cells form germinal centers (GC) and drive GC B cells to proliferate, somatically mutate, class switch, and form long-term memory, which are critical for HIV vaccine development. In addition to HIV, the vaccine platform has applications to many different viral, bacterial, and parasitic pathogens.
- Link to article: Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses.
Dr. Mohamed Abdel-Mohsen and a multidisciplinary team from Wistar, Penn and several other institutions, found that CD32, previously implicated as a marker of the HIV latent reservoir, is actually expressed preferentially on a subset of activated CD4+ T cells enriched for transcriptionally active HIV. This has important implications for identifying and targeting HIV latency in infected people. More information here.
- Link to article: CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells.
Dr. Laura Su and an international, transdisciplinary team have authored an article in Science Immunology that focuses on how follicular helper T cells (Tfh) play an essential role in shaping B-cell mediated antibody responses. The Su lab employed mass cytometry and TCR sequencing to directly examine the Tfh response to HIV and reported oligoclonal expansion of a functionally-restricted subset of Tfh cells in HIV infected lymph nodes. This lack of polyfunctionality may contribute to Tfh cell pathology in HIV infection and correlated with impaired isotype switching of B cells in the lymph nodes.
- Link to article: The receptor repertoire and functional profile of follicular T cells in HIV-infected lymph nodes.
A study led by Marcus Buggert in Mike Betts’ lab demonstrated that a unique type of CD8+ T cells residing in HIV-infected lymphoid tissue may play a critical role in long term control of HIV replication. More than 99% of viral replication occurs in lymphoid tissues, which is the key site for controlling virus. These T resident memory cells (Trm) have distinct attributes from other T cells, and may central in control of HIV. This study was enabled by key collaborations through the Reservoirs and Tissue Immunology Scientific Working Group relied on support provided by the Penn CFAR Clinical Core.
- Link to article: Identification and characterization of HIV-specific resident memory CD8+ T cells in human lymphoid tissue.
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