Cecilia J. Hillard, PhD
Associate Dean for Research; Professor; Director, Neuroscience Research Center
- 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.
(Yuan CY, Zhou V, Sauber G, Stollenwerk T, Komorowski R, López A, Tolón RM, Romero J, Hillard CJ, Drobyski WR.) Blood. 2021 Mar 04;137(9):1241-1255 PMID: 33027805 PMCID: PMC7933769 SCOPUS ID: 2-s2.0-85101859000 10/08/2020
(Alteba S, Portugalov A, Hillard CJ, Akirav I.) Neuroscience. 2021 02 10;455:89-106 PMID: 33359656 SCOPUS ID: 2-s2.0-85098975643 12/29/2020
(Knight JM, Costanzo ES, Singh S, Yin Z, Szabo A, Pawar DS, Hillard CJ, Rizzo JD, D'Souza A, Pasquini M, Coe CL, Irwin MR, Raison CL, Drobyski WR.) Transl Psychiatry. 2021 01 18;11(1):58 PMID: 33462203 PMCID: PMC7812704 SCOPUS ID: 2-s2.0-85100097244 01/20/2021
(Fitzgerald JM, Chesney SA, Lee TS, Brasel K, Larson CL, Hillard CJ, deRoon-Cassini TA.) Neurobiology of Stress. May 2021;14 SCOPUS ID: 2-s2.0-85100474357 05/01/2021
(Alteba S, Portugalov A, Hillard CJ, Akirav I.) Neuroscience. 10 February 2021;455:89-106 SCOPUS ID: 2-s2.0-85098975643 02/10/2021
(Carter GT, McLaughlin RJ, Cuttler C, Sauber GJ, Weeks DL, Hillard CJ, Weiss MD.) Muscle Nerve. 2021 01;63(1):120-126 PMID: 33094490 SCOPUS ID: 2-s2.0-85096633541 10/24/2020
(Roberts CJ, Hillard CJ.) Endocrine. 2020 Nov 20 PMID: 33216305 11/21/2020
(Vickstrom CR, Liu X, Liu S, Hu MM, Mu L, Hu Y, Yu H, Love SL, Hillard CJ, Liu QS.) Mol Psychiatry. 2020 Oct 22 PMID: 33093652 SCOPUS ID: 2-s2.0-85093837658 10/24/2020
(Sarott RC, Westphal MV, Pfaff P, Korn C, Sykes DA, Gazzi T, Brennecke B, Atz K, Weise M, Mostinski Y, Hompluem P, Koers E, Miljuš T, Roth NJ, Asmelash H, Vong MC, Piovesan J, Guba W, Rufer AC, Kusznir EA, Huber S, Raposo C, Zirwes EA, Osterwald A, Pavlovic A, Moes S, Beck J, Benito-Cuesta I, Grande T, Ruiz de Martı N Esteban S, Yeliseev A, Drawnel F, Widmer G, Holzer D, van der Wel T, Mandhair H, Yuan CY, Drobyski WR, Saroz Y, Grimsey N, Honer M, Fingerle J, Gawrisch K, Romero J, Hillard CJ, Varga ZV, van der Stelt M, Pacher P, Gertsch J, McCormick PJ, Ullmer C, Oddi S, Maccarrone M, Veprintsev DB, Nazaré M, Grether U, Carreira EM.) J Am Chem Soc. 2020 10 07;142(40):16953-16964 PMID: 32902974 SCOPUS ID: 2-s2.0-85092682450 09/10/2020
(Alteba S, Mizrachi Zer-Aviv T, Tenenhaus A, Ben David G, Adelman J, Hillard CJ, Doron R, Akirav I.) Eur Neuropsychopharmacol. 2020 10;39:70-86 PMID: 32891517 SCOPUS ID: 2-s2.0-85090150762 09/07/2020
(deRoon-Cassini TA, Stollenwerk TM, Beatka M, Hillard CJ.) Trends Mol Med. 2020 10;26(10):953-968 PMID: 32868170 PMCID: PMC7530069 SCOPUS ID: 2-s2.0-85089963030 09/02/2020
(Harfmann EJ, McAuliffe TL, Larson ER, Claesges SA, Sauber G, Hillard CJ, Goveas JS.) Psychoneuroendocrinology. October 2020;120 SCOPUS ID: 2-s2.0-85087803094 10/01/2020