Office Phone: (706) 706-721-6345

Lab Phone: (706) 721-6346

Email: dlewis@mail.mcg.edu

Office: CB3524 - Lab: CB3515

Grant Support | Current Projects | Lab | Honors & Awards | Invited Speaker | Selected Publications |

My lab is studying brain CB₁ cannabinoid receptors that are activated by cannabinoids from the marijuana plant. CB₁ cannabinoid receptors mediate retrograde signaling at synapses in many regions of the brain and have important physiological roles in analgesia, appetite and neuroprotection. To better understand the role of the CB₁ cannabinoid receptor we looked for proteins that interact with the receptor. We have recently cloned two novel, structurally-related proteins called CRIP1a and CRIP1b for cannabinoid receptor interacting proteins. Like CB₁, CRIP1a is highly expressed in the brain and occurs throughout vertebrates; whereas, CRIP1b appears to be unique to humans and other primates. Analysis of CRIP1a distribution in mouse brain reveals co-expression with CB₁ in excitatory glutamatergic neurons, but not in inhibitory GABAergic interneurons. Moreover, CRIP1a, but not CRIP1b, suppresses the tonic inhibition of voltage-gated Ca²⁺ channels by constitutively active CB₁ receptors. Collectively, our data indicate that CRIP1a regulates CB₁ signaling at excitatory synapses and may therefore be a novel target for treatment of disorders associated with excessive excitatory transmission, such as epilepsy.

NIH NIDA RO1-DA10350
"Brain Cannabinoid Receptor Signaling and Pharmacology"

• Determine the function of novel CB1cannabinoid receptor interacting proteins in the modulation of voltage-dependent Ca2+ channels using electrophysiological techniques.
• Determine whether CRIP1a can protect neurons from cell death using neuronal cultures, immunocytochemistry, lentiviral vectors to knockdown the expression of CRIP1a and Western blots to verify knockdown of CRIP1a protein.
• Find PDZ-containing proteins that interact with the C-terminus of CRIP1a and determine the role of these proteins in organizing CB1cannabinoid receptor signaling complexes.
• Determine the interaction of CB1cannabinoid receptors with specific G proteins using mutant G protein expression and functional assays

Kathleen Wallis - Research Associate. Kathleen cloned CRIP1a and is investigating its interaction with the CB1 cannabinoid receptor using molecular and proteomic techniques. Kathleen graduated from the College of Notre Dame with a BA in chemistry.

Shanping Shi - Research Assistant. Shanping is working on the structural aspects of the CB1 cannabinoid receptor that contribute to its function using molecular and electrophysiological techniques. Shanping graduated from East China University of Science and Technology with a BS in chemical engineering.

Yunguang Liu - graduate student. Yunguang is investigating the role of the novel CB1 cannabinoid receptor interacting protein, CRIP1a, in neuronal signaling using electrophysiological, molecular and immunocytochemical techniques. Yunguang graduated from Shanxi Medical University with an MD and a MS in parasitology from the Chinese Academy of Preventative Medicine. She is a Pharmacology graduate student.

Jason Niehaus - graduate student. Jason is investigating the role of the novel CB1 cannabinoid receptor interacting protein, CRIP1b, in neuronal signaling using electrophysiological, molecular and protein chemistry techniques. Jason graduated from the Georgia Institute of Technology with a BS in chemistry. He is a Pharmacology graduate student.

• Outstanding Young Faculty Award in the Basic Sciences, The Faculty of the School of Medicine, Medical College of Georgia, 1992.
• Research Excellence Award, Department of Pharmacology and Toxicology, Medical College of Georgia, 1997.
• Teaching Excellence Award, Department of Pharmacology and Toxicology, Medical College of Georgia, 1997.
• Pharmacology and Toxicology Research Award, Department of Pharmacology and Toxicology, Medical College of Georgia, 1999.
• Pharmacology and Toxicology Education Award, Department of Pharmacology and Toxicology, Medical College of Georgia, 1999.
• Pharmacology and Toxicology Faculty Teaching Award, Department of Pharmacology and Toxicology, Medical College of Georgia, 2000.
• School of Graduate Studies, Distinguished Teaching Award, 2001.
• Pharmacology and Toxicology Faculty Teaching Award, Department of Pharmacology and Toxicology, Medical College of Georgia, 2003.

February 4, 2003 "Identification of a novel protein that interacts with the CB1 cannabinoid receptor." Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY.

January 30, 2004 "Cannabinoid Receptor Interacting Proteins." Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA.

July 17-22, 2005 "CRIP1a and CRIP1b: Cannabinoid Receptor Interacting Proteins." Gordon Research Conference on Cannabinoid Function in the CNS.

November 20-23, 2005 "CB1 Cannabinoid Receptor Interacting Proteins." Third International Workshop on Ionic Channels From Structure to Pathophysiology.

October 28, 2005 "Cannabinoid receptor interacting proteins: where they are and what they do." Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA.

Pan, Xianghua, Stephen R. Ikeda and Deborah L. Lewis. SR 141716A acts as an inverse agonist to increase neuronal voltage-dependent Ca2+ currents by reversal of tonic CB1 cannabinoid receptor activity. Molecular Pharmacology 54:1064-1072, 1998.

Mahesh, Virendra B., Pedro Zamorano, Liesl De Sevilla, Deborah Lewis and Darrell W. Brann. Characterization of ionotropic glutamate receptors in rat hypothalamus, pituitary and in immortalized GnRH neurons (GT1-7 cells). Neuroendocrinology 69:397-407, 1999.

Vásquez, Clemente and Deborah L. Lewis. The CB1 cannabinoid receptor can sequester G proteins, making them unavailable to couple to other receptors. Journal of Neuroscience 19:9271-9280, 1999.

Nie J. and Lewis D.L. The proximal and distal C-terminal tail domains of the CB1 cannabinoid receptor mediate G protein coupling. Neuroscience 107: 161-167, 2001.

Nie, Jingjiang and Deborah L. Lewis. Structural domains of the CB1 cannabinoid receptor that contribute to constitutive activity and G protein sequestration. Journal of Neuroscience 21:8758-8764, 2001.

Silva, Jeane M. and Deborah L. Lewis. Nitric oxide enhances Ca2+-dependent K+ channel activity in rat carotid body cells. Pflügers Arch European Journal of Physiology, 443:671-675, 2001.

Dow P. Hurst, Diane L. Lynch, Judy Barnett-Norris, Stephen M. Hyatt, Herbert Seltzman, Miao Zhong, Zhao-Hui Song, Jingjiang Nie, Deborah L. Lewis and Patricia H. Reggio. N - Piperidin-1-yl)- 5 -(4-chlorophenyl)- 1 -(2,4-dichlorophenyl)- 4 -methyl-1H-pyrazole- 3 -carboxamide (SR141716A) interaction with Lys 3.28 (192) is crucial for its inverse agonism at the cannabinoid CB1 receptor. Molecular Pharmacology, 62:1274-1287, 2002.

Vásquez, C. and Deborah L. Lewis. The b2-adrenergic receptor specifically sequesters Gs in rat sympathetic neurons. Neuroscience, 118:603-610, 2003.

Lewis, Deborah L. Cannabinoid receptor G protein-coupling and inverse agonism. Current Neurophamacology, 2:31-36, 2004.