Amphetamine abuse focus:
Drug-induced overdose deaths linked to amphetamines (AMPHs) have risen sharply over the last decade, reaching over 30,000 per year in 2021. AMPHs target the dopamine transporter (DAT) to elicit their behavioral effects. DAT is a plasma membrane protein that removes dopamine (DA) from the extracellular space, following firing of DA neurons, by importing DA back inside presynaptic neurons. AMPHs, interestingly, cause reversal of DAT. So instead transporting DA back inside neurons, in the presence of AMPH, DAT actively pumps DA outside of the cell (DA efflux), thereby driving DA neurotransmission. This efflux is strongly associated with the psychomotor stimulant and reward properties of both AMPHs. Unfortunately, there are currently no FDA approved treatments for AMPH use disorders. Our lab is interested in uncovering novel regulatory nodes for responses to AMPHs in order to open new avenues for the development of future therapeutics.
1. Fusobacterium nucleatum as an enhancer of AMPH addiction.
This work aims to delineate the molecular mechanisms behind the ability of F. nucleatum to enhance AMPH-induced DA efflux and AMPH-associated behaviors such as locomotion, sexual motivation, and AMPH preference.
2. Microbial biofilms as regulators of AMPH use disorders.
The goal of this work is to understand to role of multispecies biofilm formation in colonization of the host by F. nucleatum, how this modulates host responses to AMPH, and what bacterial pathways are important for this process.
Hormonal syndromes focus:
Development of slow growing neuroendocrine tumors (NET) is rare, however, due to high survival rates of patients, NETs are the second most common solid tumor. NETs of surviving patients often cause severe morbidity due to excessive secretion of bioactive hormones from tumor cells. NETs that secrete large amounts of serotonin into the bloodstream elicit severe diarrhea that leads to malnutrition and weight loss (carcinoid syndrome) in combination with extreme disruption of normal life activities. Furthermore, carcinoid syndrome patients often develop cardiac fibrosis that can lead to eventual heart failure. NETs that secrete insulin into the bloodstream disrupt glucose homeostasis and result in hypoglycemia that can lead to sweating, heart palpitations, seizures and potentially coma.
3. Engineered microbes as therapeutic factories for treatment of severe hormonal syndromes.
The goal of this work is to engineer attenuated Salmonella strain VNP20009 to form persistent colonies specifically in the NET microenvironment and secrete enzymes capable of local hormone degradation, thus reducing systemic release of hormone and alleviating hormonal side effects.
Cancer focus:
4. Viral transduction of synthetic “response” genes for treatment of glioblastoma.
This work, in collaboration with multiple UAB CINEMA investigators, aims to engineer a system to induce apoptosis in glioblastoma cells using X-rays in combination with viral expression of recombinant regulatory proteins.
