Cecilia J. Hillard, PhD
Associate Dean for Research; Professor; Director, Neuroscience Research Center; G. Frederick Kasten, Jr. Endowed Chair in Parkinson’s Disease Research
- Pharmacology and Toxicology
BS, Chemistry, University of Virginia, 1977
Dr. Hillard was named Associate Dean for Research in November 2015 after serving eight months as co-Interim Senior Associate Dean for Research. She has served as director of the Neuroscience Research Center since its inception in 2010. She was also Inaugural Director of the Neuroscience Graduate Training Program from 1996-2010. As a highly active researcher, Dr. Hillard’s laboratory is primarily focused on the pharmacology and biochemistry of the cannabinoids and endocannabinoids. Her significant bibliography and frequent invitations to present attest to her reputation as a leader in her field. Dr. Hillard is an MCW graduate and a true advocate for the Basic Sciences. Frequently named an Outstanding Medical Student Teacher, Dr. Hillard takes an active role in training and mentorship, receiving MCW’s highest honor, the Distinguished Service Award, in 2011.
Dr. Hillard was recently awarded the Lifetime Achievement Award from the International Cannabinoid Research Society. Dr. Hillard is a member of both the Society of Teaching Scholars and the Society for Research Excellence at MCW.
- Cannabinoid Receptor Agonists
- Cannabinoid Receptor Modulators
- Carrier Proteins
- Cells, Cultured
Marijuana has been used by humans for more than 2,500 years as a medicinal agent and social drug. Cannabinoids are the chemicals in marijuana that are responsible for its effects on the body. A long-standing interest of our laboratory is the study of the mechanisms by which the cannabinoids affect the function of the brain. Delta-9-tetrahydrocannabinol (THC) is the cannabinoid in marijuana that is responsible for its mood- and sensation-altering effects. THC targets two receptors: the CB1 receptor present on neurons and the CB2 receptor that is present primarily on immune cells. Although THC targets these receptors when a person is exposed to the drug from the outside, we know that at least two “endogenous” (or, from the self) molecules also target these receptors. These two molecules are named the endocannabinoids. Our research focuses on the cannabinoids, the receptors with which they interact and the role of the endocannabinoids in brain function.
We have three major research projects:
Studies of the biochemical mechanisms involved in the synthesis, release and degradation of the endocannabinoids
At least two lipid molecules are thought to act as endocannabinoids, anandamide and 2-arachidonoylglycerol. Both can be synthesized by neurons but our knowledge of the mechanisms that regulate their synthesis is lacking in detail. One goal of our work is to develop inhibitors of these pathways to help us understand the physiological roles of endocannabinoids. We are also studying the processes by which the endocannabinoids are inactivated. We know that they are catabolized by enzymes and that they are substrates for transporters that act in plasma membranes. One of our goals is to biochemically understand these processes and to develop inhibitors.
Studies of the role of endocannabinoid signaling in the regulation of mood and responses to stress
Several laboratories, including ours, have demonstrated that one very important function of the endocannabinoids is to regulate the response of the brain to stress. Animals and humans need to cope with physical and psychological stresses in order to survive, but stress responses have a cost. For example, we know that long term stress exposure results in depression and post traumatic stress disorder in humans. The endogenous cannabinoid system is a stress buffer, it turns down the hormonal and behavioral responses to stress. In addition, the endocannabinoid system is itself turned on or, in some cases, turned off by stress. Our goal in these studies is to examine the mechanistic relationships between stress and the endocannabinoids. While most of our studies are carried out using rodent models, we are also exploring these processes in human subjects exposed to periods of psychological stress through collaborations with other investigators.
Roles of cannabinoids in regulation of the immune response
Signaling through the CB2 receptor has been shown to reduce activation of the immune system. Although immune cell activation is vital to fight infections, excess or inappropriate immune activation contributes to many important and devastating diseases, including multiple sclerosis and graft-versus-host disease, which can occur after bone marrow transplants to treat cancer. Our laboratory is exploring the roles of CB2 receptors and the phytocannabinoid, cannabidiol, in neuroinflammation and graft-versus-host disease models.
Altered glial expression of the cannabinoid 1 receptor in the subiculum of a mouse model of Alzheimer's disease.
(Terradillos I, Bonilla-Del Río I, Puente N, Serrano M, Mimenza A, Lekunberri L, Anaut-Lusar I, Reguero L, Gerrikagoitia I, Ruiz de Martín Esteban S, Hillard CJ, Grande MT, Romero J, Elezgarai I, Grandes P.) Glia. 2023 Apr;71(4):866-879 PMID: 36437738 SCOPUS ID: 2-s2.0-85142903688 11/29/2022
Associations between socioeconomic status and bispecific LV20.19 CAR T-cell therapy outcomes.
(Knight JM, Hackett E, Szabo A, Wu R, Sauber G, Johnson B, Cusatis RN, Aughey E, Cole SW, Hillard CJ, Shah NN.) Haematologica. 2023 Feb 01;108(2):588-593 PMID: 36200427 PMCID: PMC9890001 SCOPUS ID: 2-s2.0-85147234722 10/07/2022
Circulating endocannabinoids and psychological outcomes in women with PTSD
(Botsford C, Brellenthin AG, Cisler JM, Hillard CJ, Koltyn KF, Crombie KM.) Journal of Anxiety Disorders. January 2023;93 SCOPUS ID: 2-s2.0-85143352081 01/01/2023
Circulating endocannabinoids and psychological outcomes in women with PTSD.
(Botsford C, Brellenthin AG, Cisler JM, Hillard CJ, Koltyn KF, Crombie KM.) J Anxiety Disord. 2023 Jan;93:102656 PMID: 36469982 PMCID: PMC9839585 SCOPUS ID: 2-s2.0-85143352081 12/06/2022
Peripheral sensory neuron CB2 cannabinoid receptors are necessary for both CB2-mediated antinociceptive efficacy and sparing of morphine tolerance in a mouse model of anti-retroviral toxic neuropathy.
(Carey LM, Xu Z, Rajic G, Makriyannis A, Romero J, Hillard C, Mackie K, Hohmann AG.) Pharmacol Res. 2023 Jan;187:106560 PMID: 36417942 PMCID: PMC9845180 SCOPUS ID: 2-s2.0-85142686286 11/24/2022
Endocannabinoid signaling in the central nervous system.
(Martinez Ramirez CE, Ruiz-Pérez G, Stollenwerk TM, Behlke C, Doherty A, Hillard CJ.) Glia. 2023 Jan;71(1):5-35 PMID: 36308424 PMCID: PMC10167744 SCOPUS ID: 2-s2.0-85141398970 10/30/2022
FAAH Inhibition Restores Early Life Stress-Induced Alterations in PFC microRNAs Associated with Depressive-Like Behavior in Male and Female Rats.
(Portugalov A, Zaidan H, Gaisler-Salomon I, Hillard CJ, Akirav I.) Int J Mol Sci. 2022 Dec 17;23(24) PMID: 36555739 PMCID: PMC9782513 SCOPUS ID: 2-s2.0-85144537750 12/24/2022
Machine learning prediction of posttraumatic stress disorder trajectories following traumatic injury: Identification and validation in two independent samples.
(Tomas CW, Fitzgerald JM, Bergner C, Hillard CJ, Larson CL, deRoon-Cassini TA.) J Trauma Stress. 2022 Dec;35(6):1656-1671 PMID: 36006041 SCOPUS ID: 2-s2.0-85136599889 08/26/2022
Fatty acid amide hydrolase activity in the dorsal periaqueductal gray attenuates neuropathic pain and associated dysautonomia.
(Woyach V, Sherman K, Hillard CJ, Hopp FA, Hogan QH, Dean C.) Am J Physiol Regul Integr Comp Physiol. 2022 Nov 01;323(5):R749-R762 PMID: 36154489 PMCID: PMC9639763 SCOPUS ID: 2-s2.0-85141004185 09/27/2022
Editorial: Therapeutic potential of the cannabinoid CB2 receptor.
(Smoum R, Grether U, Karsak M, Vernall AJ, Park F, Hillard CJ, Pacher P.) Front Pharmacol. 2022;13:1039564 PMID: 36278235 PMCID: PMC9585503 10/25/2022
Editorial: Therapeutic potential of the cannabinoid CB2 receptor
(Smoum R, Grether U, Karsak M, Vernall AJ, Park F, Hillard CJ, Pacher P.) Frontiers in Pharmacology. 7 October 2022;13 SCOPUS ID: 2-s2.0-85140462458 10/07/2022
The influence of depression on the relationship between loneliness and grief trajectories in bereaved older adults.
(Reiland H, Banerjee A, Claesges SA, Giuca AM, Hillard CJ, Reynolds CF 3rd, Goveas JS.) Psychiatry Res Commun. 2021 Oct;1(1) PMID: 35928209 PMCID: PMC9345326 08/06/2022