The lab investigates the molecular and cellular basis of neurocognitive impairment associated with neuroinflammation and neuroimmune disease, with a main focus on HIV-associated neurocognitive disorders. Despite the benefits of modern antiretroviral therapy, the neurological complications of HIV are still frequent and often aggravated by substance abuse, aging and comorbidities. Therefore, the need for targeted adjuvant therapies remains, and is enhanced by the extended life span of treated patients. Our findings indicate that harnessing the power of homeostatic chemokines can mitigate cognitive impairment.

Chemokines are a class of small, secreted proteins well known for their function in immune surveillance and inflammatory responses. However, they also play key roles in the development and homeostasis of other organ systems, including the CNS and the cardiovascular system. Imbalances in chemokine expression or altered function are often associated with CNS pathology and other maladies.

Briefly, our studies have been centered on the effects of viral proteins, inflammatory mediators and opioids on the brain, with particular attention to the interplay with chemokines and their G protein coupled receptors. Ongoing projects are examining:

• The effects of selected chemokine/receptor pairs on neurons and glia, under various physiological and pathological conditions
• The interaction between chemokines and opioid use
• The molecular mechanisms involved in HIV-induced synaptic/dendritic alterations, and the ensuing impairment in cognitive behavior

Importantly, these studies also have implications for other neuropsychiatric disorders, such as schizophrenia, Alzheimer’s, pain and addiction.

Another area of interest concerns CNS complications of cancer progression and therapy. Specifically, we have been focusing on chemokine-dependent mechanisms in inflammatory breast cancer, a rare and aggressive form of cancer typically diagnosed in advanced stage that often metastasizes to the brain. In collaborations with other groups at Drexel University, we developed a new class of small molecule chemokine receptor inhibitors that show promise for treatment of IBC. We are currently testing these proprietary compounds in preclinical IBC models, in preparation for IND filing.

To learn more about the lab and our projects, please visit the extended lab website.

 
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