Dr. Unwalla’s current research focuses on understanding the role of aberrant microRNAs in health and disease.

Specifically, the laboratory focuses on the role of aberrant microRNAs in HIV biology that contributes to non-AIDS comorbidities. In aging HIV-infected populations, comorbid diseases are important determinants of morbidity and mortality. The combination of antiretroviral therapy has made HIV a treatable disease. However, HIV patients die of non-AIDS comorbidities almost a decade earlier than their non-HIV counterparts. Lung diseases such as COPD, pulmonary hypertension, and pneumonia are emerging as significant comorbidities in the HIV-infected population This is exacerbated in HIV patients who are addicted to nicotine and smoke tobacco. We have shown that HIV infection and cigarette smoking promote an aberrant microRNAome that can play a causal role in the development of COPD in people living with HIV and in smokers by promoting airway inflammation. Aberrant microRNAs may also play a causal role in linking diabetes, obesity, and cigarette smoking, to the development of Alzheimer’s disease.

Research in Unwalla’s laboratory focuses on three different projects:

  1. MicroRNAs play an important role in health and disease and are easily dysregulated in response to environmental stimuli. The laboratory has reported that HIV infection and/or cigarette smoking promotes an aberrant microRNAome in bronchial epithelium which can dysregulate expression of genes involved in airway innate immune mechanisms, mitochondrial homeostasis and tissue circadian clocks. Altered homeostasis in the expression of these genes can trigger multifactorial pathways that can lead to airway inflammation and development of COPD. Understanding these causal events can help identify interventions to mitigate lung inflammation and arrest lung function decline in COPD. These projects is supported by an NIH R01 (HIV) and a Florida department of health grant (tobacco smoking).
  2. Another project in the laboratory focuses on developing inducible CRISPR systems to “shock and lock” HIV in infected cells. Prior research has shown that antivirals targeting the HIV nucleic acid sequence like siRNAs and CRISPR have a high failure rate due to the ability to mutate and escape inhibition by these anti-HIV strategies. Targeting cellular factors pivotal to HIV replication provides an alternative way to make these mutations irrelevant. Given, the important roles of these factors, the laboratory has developed a Pol II based mono-promoter HIV inducible CRISPR system targeting cellular factors such that expression of the CRISPR system and inhibition is only observed in HIV infected cells to lock the virus in a transcriptionally inactive state and achieve a functional cure. This project is supported by a Department of Defense grant.
  3. A recent project in the laboratory tries to determine the role of aberrant microRNAomes in promoting Alzheimer’s disease. Diabetes, obesity, and cigarette smoking are important risk factors for Alzheimer’s disease. However, the mechanisms by which these risk factors promote Alzheimer’s disease are poorly understood. The project will identify changes in microRNA expression in the brain mediated by these risk factors and the downstream effects of these miRNAs on genes involved in controlling neuroinflammation.