Binhua “Julie” Ling, M.D., M.Med.Sc., Ph.D.
Professor, Program Lead – Host Pathogen Interactions
Research Focus
Dr Ling’s laboratory focuses on simian immunodeficiency virus (SIV) and chimeric simian-human immunodeficiency viruses (SHIVs) in nonhuman primates to study HIV persistence and reservoir in tissues, particularly lymphoid tissues and the central nervous system (CNS). This research aims to develop novel drug delivery and therapeutic strategies for HIV eradication as a potential cure. The team also seeks to understand the factors that control or spread the virus in a host, both with and without therapeutic intervention. Additional interests include HIV and aging, HIV persistence and the gut microbiome, and HIV-related substance use disorders. Dr. Ling has a broad background in molecular virology and immunology, with many years of experience and expertise in nonhuman primate models focused on HIV/SIV pathogenesis and cure research.
Inside the Lab
HIV/SIV persistence in lymphoid tissues.
Her study of gut tissue reservoir revealed large intestine and mesenteric lymph nodes are major reservoirs in spontaneous controllers (SC) and animals on potent combination antiretroviral therapy (cART). The lab further explores dynamic changes of gut microbiota and immune activation during long-term cART that may contribute to SIV persistence. Working with collaborators, novel strategies of delivery of potent drugs to the gut and mesenteric lymph nodes are also in development.
Viral reservoirs in the CNS.
Persistence of HIV in the CNS is another obstacle to a HIV cure. Current studies include the role of myeloid cells as cellular reservoirs and the potential source of viral rebound in the CNS, as well as the use of novel technologies such as CRISPR-Cas 9 editing system to test the potential for eradication of the virus in infected cells.
Host responses in immune protection and correlation.
Previous studies showed that SIV/cRM model is featured with a relatively high frequency of SC similar to HIV-infected long term non-progressors. Her team continuously work to understand the mechanism(s) of immune correlates with this slower progression with or without therapy, particularly the role of NK cells during early infection, for novel therapeutics.
HIV/SIV and aging.
HIV infection may play a role in accentuated and/or accelerated aging such as age-associated neurocognitive dysfunction. The team uses the SIV-infected rhesus macaques on cART to determine factors such as SIV and antiretroviral drugs themselves contribute to sustained neuroinflammation, cellular senescence and senescence-associated secretory phenotype (SASP) in brain aging in the nonhuman primate model of HIV infection on cART.
Main Technologies and Methods Used
Cell culture
Viral immunology
Flow cytometry and cell sorting
In situ hybridization, RNAscope
Immunofluorescence, confocal microscopy
CRISPR and other gene editing technologies in vivo application
Quantitative PCR, qRT-PCR, ddPCR, deep sequencing, and transcriptomics