The primary focus of my laboratory is to understand the mechanisms responsible for endocannabinoid signaling in human health and disease including cannabinoid tolerance, drug addiction, and metabolic homeostasis. Currently my group is funded by NIDA to assess the mechanisms responsible for cannabinoid tolerance (DA044999). This work involves assessing the contribution and molecular mechanisms of c-Jun N-terminal kinase (JNK) signaling in tolerance for different cannabinoid drugs. We are also actively engaged in work to understand the mechanisms responsible for sex differences between male and female mice in the response and tolerance to cannabinoids. This work involves using different strains of mutant mice that express either desensitization or internalization-resistant forms of the cannabinoid type 1 receptor. Members of my group commonly use methods in behavioral pharmacology to assess acute, inflammatory, and chronic pain in mice and molecular pharmacological approaches to assess cannabinoid receptor function and signaling. These pain testing approaches include the tail-flick and hotplate tests to measure acute pain, the formalin test to measure inflammatory pain, and the von Frey, Hargraeve's, and acetone tests to measure mechanical and thermal sensitivity in mice with chronic pain from chemotherapy exposure or nerve injury. We also use the elevated plus maze, forced swim test, conditioned place preference, and ultrasonic vocalizations to measure affective components of chronic pain. Lab members use molecular approaches such as qRT-PCR, Western Blotting, radioligand binding, and agonist-stimulated G protein activation to probe receptor expression and function.
A second project that we are interested in involves understanding the role of neuropeptide signaling in the regulation of pain and motivated behaviors such as drug addiction and feeding. This work focuses on assessing the role of small neuropeptides derived from a protein precursor protein called proSAAS. ProSAAS-derived peptides have been shown to signal through two recently deorphanized G protein-coupled receptors, GPR171 and GPR83, to modulate body weight, feeding behavior, morphine tolerance and reward, and anxiety behaviors. Our current work involves examining acute, inflammatory, and chronic pain as well as morphine tolerance in mutant mice lacking proSAAS. Finally, a third project involves assessing the impact of decursinol, the active anti-inflammatory and antinociceptive natural product component from the Korean Angelica Gigas Nakai plant, in acute, inflammatory, and chemotherapy-evoked chronic pain. Current work on this project involves assessing whether tolerance develops to the pain-relieving effects of decursinol and also whether co-administering this natural compound with chemotherapy might prevent development and "chronification" of neuropathic pain. My goals also include providing the highest level of mentorship to my trainees and to help recruit and develop women and members of underrepresented groups so that they can obtain tenure track faculty positions in academia or equivalent senior positions in biotechnology or the pharmaceutical industry.
Angela Henderson Redmond - Research Assistant Professor
Mary Piscura - Graduate Student
LaTaijah Crawford - Graduate Student
Courtney Lulek - Undergraduate Researcher