CPRI COBRE Ignite Scholars
Current Scholars
Discovery and Development of Cyanobacterial Natural Products as Analgesics
Kevin Tidgewell, Ph.D. Assistant Professor, Department of Pharmaceutical Sciences
July 2023 - present
There is a pressing need to develop novel therapeutic agents against new targets for chronic pain. This project will use cyanobacterial-derived natural products as the starting point for chronic neuropathic pain drug development by targeting the sigma 2/transmembrane protein 97 (σ-2/TMEM97) receptor and other targets involved in pain. The σ-2/TMEM97 receptor has been pharmacologically known for over 40 years but only since 2017 has the molecular identity and its possible role in pain been described. With a new crystal structure σ-2/TMEM97 and five studies describing the potential of σ-2/TMEM97 modulators to treat pain in rodents, this will be an area of rapid exploration and development in the coming years. Our preliminary data show selectivity of proof-of-concept cyanobacterial natural products for σ-2/TMEM97 as well as data showing analgesic effects in mice with potential to modulate human “nociceptors” in vitro with mechanisms of action identified in primary mouse dorsal root ganglion neurons. Loss of σ-2/TMEM97 leads to enhanced recovery from inflammatory pain suggesting a normally pro-nociceptive role of σ-2/TMEM97. Using cyanobacterial natural products and synthetic analogs, this project will yield i) explore their binding to and modulation of the σ-2/TMEM97 receptor and ii) improve understanding of the pharmacological and biological role of σ-2/TMEM97 in human nociceptors.
Mentors: Jurgen Rohr, Pavel Ortinski
Understanding neuropeptide targets within extended amygdala circuits for the treatment of anxiety and stress disorders
Anel Jaramillo, Ph.D. Assistant Professor, Department of Pharmaceutical Sciences
February 2023 - present
Heightened anxiety and dysregulated behavioral responses to stress are key features of neuropsychiatric mood disorders (e.g., PTSD). To inform the development of effective treatments our lab investigates the mechanisms underlying heighted anxiety by combining sophisticated measures of neurocircuit activity with classic behavioral assays in rodent models. This project will investigate inhibition of stress-related neuropeptides as a target for alleviating dysregulated anxiety-like behavior and circuit activity in the extended amygdala, a core component of anxiety circuitry.
Mentors: Jill Turner, Ilhem Messaoudi Powers
Former Ignite Scholars
Dysregulation of bile acid homeostasis in obesity pathogenesis
Lindsay Czuba, Ph.D.
Assistant Professor, Department of Pharmaceutical Sciences
September 2022 - February 2024
Progressive human obesity is associated with systemic dysregulation of cholesterol, oxysterol, and bile acid homeostasis and is a leading cause of NAFLD, diabetes, and cardiovascular disease. Bile acids and their metabolites serve as ligands for nuclear receptors such as the farnesoid X receptor (FXR) and liver X receptor (LXR) to transcriptionally regulate lipid and cholesterol homeostasis. Gut commensal bacteria contribute significantly to the metabolism of bile acids to produce secondary bile acid metabolites. However, little is known about the individual contributions of bile acids and their secondary metabolites to gut-liver signaling and metabolic effects. Early work in the lab aims A) to identify the affinity and activity of secondary bile acid metabolites towards FXR and the bile acid transporter, ASBT and B) to develop LC-MS/MS methods to quantify bile acid metabolites and oxysterols in gut and liver tissue. Findings from these projects will provide foundational knowledge on the role of bile acid metabolites in mediating bile acid, cholesterol, and lipid homeostasis and inform future translational research on human obesity pathogenesis and its metabolic comorbidities.
Mentors: Barbara Nikolajczyk, Bjoern Bauer
We wish to remember and honor those who inhabited this Commonwealth before the arrival of the Europeans. Briefly occupying these lands were the Osage, Wyndott tribe, and Miami peoples. The Adena and Hopewell peoples, who are recognized by the naming of the time period in which they resided here, were here more permanently. Some of their mounds remain in the Lexington area, including at UK’s Adena Park.
In more recent years, the Cherokee occupied southeast Kentucky, the Yuchi southwest Kentucky, the Chickasaw extreme western Kentucky and the Shawnee central Kentucky including what is now the city of Lexington. The Shawnee left when colonization pushed through the Appalachian Mountains. Lower Shawnee Town ceremonial grounds are still visible in Greenup County.
We honor the first inhabitants who were here, respect their culture, and acknowledge the presence of their descendants who are here today in all walks of life including fellow pharmacists and healthcare professionals.