I am interested in studying arthropod-associated congenital viral infections that are major public concerns to fetal health, particularly due to the significant risk of epidemics causes by arboviruses. Zika virus (ZIKV) infection during pregnancy causes fetal microcephaly and other neurologic sequelae, which impacts early childhood development. The re-emergence of ZIKV, most recently the 2015-2016 outbreak in the Americas, caused thousands of cases globally and demonstrated how rapidly an arbovirus can expand into new territories and impact humans.
Our work uses highly translatable nonhuman primate (NHP) models of ZIKV maternal-to-fetal transmission and acute ZIKV infection to advance and develop our understanding of arboviral infection linked with microcephaly and viral persistence in immune-privileged tissue sites. We have identified perturbations to the oligodendrocyte lineage in the fetal brain that is an underlying pathology of congenital Zika syndrome. We have also found a significant impact to the male reproductive tract (MRT) following acute ZIKV infection, with ZIKV pathogenesis associated with tissue pathology and decreased spermatogenesis.
My research uses immunohistologic and molecular techniques, including RNA sequencing and spatial transcriptomics, to define the tissue responses to viral infection linked with distinct pathophysiology of brain and MRT infections. This includes the use of human cell culture models to further understand the mechanisms of viral infection in the brain and testes that will also serve as a mechanistic model to evaluate therapeutic targets to mitigate viral infection and immunopathology.
Ongoing research focus areas include:
1. Understanding Zika virus infection at the maternal-fetal interface and mechanisms of Zika virus-
induced microcephaly to identify neuroprotective measures for improved fetal health.
2. Evaluating the impact of ZIKV infection in the brain, with particular focus on oligodendrocyte
responses and differentiation using human cell culture systems and a preclinical model of
maternal-fetal ZIKV transmission to examine the virus-host interactions of ZIKV that underlie
vertical transmission and fetal disease
3. Retrospective analysis of virus-infected macaque archival tissue samples from acute and
convalescent phases of infection to investigate immune responses in tissues and blood.
4. Application of multi-scale and multi-modal approaches for the characterization of virus-host
interactions to define pathological profiles of brain injury underlying congenital Zika syndrome and
mechanisms of viral persistence
