Richard M. Van Rijn
Ph.D. (2007): Molecular Pharmacology - VU University Amsterdam
Postdoc. (2007-2013): Ernest Gallo Clinic and Research Center Department of Neurology - University of California San Francisco
In my laboratory we use innovative strategies and techniques to provide a better understanding of the molecular mechanism by which G-protein coupled receptors (GPCRs) function, propagate signal transduction and modulate behavior. GPCRs form the largest protein family in the human genome and are crucial in relaying extracellular information into the cell. GPCRs are involved in many diverse physiological responses, including light perception, taste, immune responses, cardiovascular activity and neurotransmission. Currently, 30-40% of all drugs, approved by the Federal Drug Administration, target GPCRs. New insights into how these receptors work have re-energized the study of these receptors. Specifically, we study biased receptor signaling and GPCR heteromerization and potential overlap of these concepts and their roles in (patho)-physiological responses. We frequently use the delta opioid receptor as model receptor for our studies. We use a combination of in vitro cell culture assays, with in vivo mouse behavioral paradigms and ex vivo assays to perform translational/pre-clinical research with the goal of proposing and developing new therapeutic drugs that may have better potency, efficacy and fewer side effects. Our main focus is on neurological disorders, with an emphasis on drug addiction and co-morbid mood and anxiety disorders as well as chronic pain conditions. Current projects involve investigations into the risk of the alcohol mixed energy drinks, the role of beta-arrestin dependent signaling in depression and anxiety disorders, the physiological function of opioid-dopamine interactions and alcohol withdrawal induced hyperalgesia.
MCMP544: Drug classes and mechanisms
PHRM845: Integrated Pharmacotherapy III
PHRM316: Drug abuse/addiction education
IUSM610: Basic Principles of Pharmacology & Toxicology I
IUSM611: Basic Principles of Pharmacology & Toxicology II
Purdue Institute for Inflammation, Immunology and Infectious Diseases 9/1/2016-08/31/2017
AC1 inhibitors for treatment of (opioid resistant inflammatory pain
The primary objective of this grant is to test a small molecule selective inhibitor of adenylyl cyclase I for treatment of (opioid resistant) arthritic pain.
NARSAD young investigator grant 07/15/2016 – 07/14/2018
Development of novel designer G-protein coupled receptors to study the role of β-arrestin2 biased signal transduction in anxiety disorders.
The primary objective is to develop β-arrestin 2 biased designer receptors (DREADDs) and locally express them in brain areas involved in anxiety-like behavior.
NIAAA R00 (A020539) 09/05/13 – 08/31/16
Development of a preclinical candidate for the treatment of alcoholism
The primary objective of this grant is to validate a DOR-subtype as a new target for intervention in alcohol abuse and determine the properties of the most ideal DOR-subtype selective drug to develop it as a preclinical lead.
Ralph W. and Grace M. Showalter Research Trust 07/01/14-06/30/15
New mechanism for modulating opioid receptor mediated analgesia
The primary objective of this grant is to investigate the delta-mu heteromer interface and ways to manipulate the formation of these heteromers to study its function in pain disorders.
- Brust TF, Alongrkronrusmee D, Soto-Velasquez M, Baldwin TA, Ye Z, Dai M, Dessauer CW, Van Rijn RM, Watts VJ, Identification of a selective small-molecule inhibitor of type 1 adenylyl cyclase activity with analgesic properties, 2017, Sci Signal, 10(467), eaah5381, Covered in Science magazine
- Zeng L, Alongkronrusmee D, Van Rijn RM, An integrative perspective on diabetic, alcoholic and drug-induced neuropathic pain, J Pain Res, 2017, 10, 219-228. "Noteworthy" designation
- Anastasia AD, Selzer CC, Elantably H, van Rijn RM, Krause JE, Heroin Use Disorder: The evolving role of the pharmacist, Indiana Pharmacist Alliance, continued professional education (CPE), 2016, #5
- Alongkronrusmee D, Chiang T, Van Rijn RM, Delta opioid receptors as target to treat alcohol withdrawal induced hyperalgesia. 2016, Drug Alcohol Depend, 167, 190-198
- Yang S, Ben-Shalom R, Ahn M, Liptak AT, van Rijn RM, Whistler JL, Bender KJ, Beta-Arrestin-dependent dopaminergic regulation of calcium channel activity in the axon initial segment, 2016, Cell Rep, 16 (6), 1518-1526
- Robins MT, Lu J, Van Rijn RM, Unique behavioral and neurochemical effects induced by repeated adolescent consumption of caffeine-mixed alcohol in C57BL/6 mice, 2016, Plos One, 11(7):e0158189
- Robins MT, DeFriel JN, Van Rijn RM, adolescent intake of caffeinated energy drinks does not affect adult alcohol consumption in C57BL/6 and BALB/c mice, 2016, Alcohol, 54, 1-9
- Alongkronrusmee D, Chiang T, Van Rijn RM, Role of delta opioid receptor pharmacology in alcohol behaviors, Handbook of Experimental Pharmacology on Delta Opioid Receptor Pharmacology, Springer, 2016
- Chiang T, Sansuk K, Van Rijn RM, Beta-arrestin 2 dependence of delta opioid receptor agonists is correlated with alcohol intake. Br. J. Pharmacol., 2016, 173(2), 332-343
- Van Rijn RM, DeFriel JN, Whistler JL, Pharmacological traits of delta opioid receptors: pitfalls or opportunities, Psychopharmacol, 2013, 228 (1), 1-18
- Milan-Lobo L, Enquist JE, Van Rijn RM, Whistler JL, anti-analgesic effect of the mu/delta opioid receptor-heteromer revealed by ligand-biased antagonism, 2013, Plos One, 8(3): e58362, PMC3598907
- Harvey JH, Van Rijn RM, Whistler JL, High-throughput screening of GPCR heteromer-specific ligands using a FLIPR calcium mobilization assay, 2013, Humana Press, Springer, Methods Mol Biol, 995, Chemical Neurobiology: 43-54
- Van Rijn RM, Harvey JH, Brissett DI, DeFriel JN, Whistler JL, Novel screening assay for the selective detection of G protein-coupled receptor heteromer signaling, J Pharmacol Exp Ther, 334(1):179-188, Highlighted paper
- Van Rijn RM, Brissett DI, Whistler JL, Distinctive modulation of ethanol place preference by delta opioid receptor selective agonists, 2012, Drug Alcohol Depend, 2012, 122(1-2):156- PMC3279630
- Brissett DI, Whistler JL, Van Rijn RM, Contribution of mu and delta opioid receptors to the pharmacological profile of kappa opioid receptor subtypes, Eur. J Pain, 2012, 16 (3): 327-337
- Van Rijn RM, Brissett DI, Whistler JL, Emergence of functional spinal delta-mu opioid receptors heteromers after chronic ethanol exposure, Biol Psychiatry, 2012, 71:232-238
- Van Rijn RM, Brissett DI, Whistler JL, Dual efficacy of delta opioid selective ligands for ethanol drinking and anxiety, J Pharmacol Exp Ther, 2010, 335 (1):133-139, PMC2957775
- Van Rijn RM, Whistler JL, Waldhoer M, Opioid receptor heteromer-specific trafficking and pharmacology, Curr Opin Pharmacol, 2010, 10:73-79, PMC2900797
- Van Rijn RM, Whistler JL. The delta-1 opioid receptor is a heterodimer that opposes the actions of the delta-2 receptor on alcohol intake, Biol. Psychiatry, 2009, 66:777-784, PMC2757485
- He L, Kim J, Ou C, McFadden Van Rijn RM, Whistler JL, Methadone antinociception is dependent on peripheral opioid receptors, J Pain, 2009, 10(4):369-379
- Van Rijn RM, Whistler JL, The only way is up: preventing opioid tolerance by promoting cell surface expression of MOR-DOR heterodimers? Mol. Interv, 2008, 8 (6): 277-280
- Van Rijn RM, van Marle A, Chazot PL, Langemijer E, Qin Y, Shenton FC, Lim HD, Zuiderveld OP, Sansuk K, Dy M, Smit MJ, Tensen CP, Bakker RA, Leurs R, Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor, Biochem J, 2008, 414 (1):121-131
- Van Rijn RM, Chazot PL, Shenton FC, Sansuk K, Bakker RA, Leurs R, Oligomerization of recombinant and endogenously expressed human histamine H4 receptors, Mol. Pharmacol. 2006, 70(2):604-15
- Bakker RA, Lozada AF, van Marle A, Shenton FC, Drutel G, Karlstedt K, Hoffmann M, Lintunen M, Yamamoto Y, van Rijn RM, Chazot PL, Panula P, Leurs R, Discovery of naturally occurring splice variants of the rat histamine H3 receptor that act as dominant negatives, Mol. Pharmacol, 2006, 69(4):1194-206.
- Lim, HD1 and Van Rijn RM1, Ling P, Bakker RA, Thurmond RL, Leurs R., Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther. 2005, 4(3):1310-21.