Roh-Yu Shen PhD
Roh-Yu Shen
PhD
Professor
Department of Pharmacology and Toxicology
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Addictions; Behavioral Neuroscience; Brain Research; Drug Abuse; Electrophysiology; Ethanol Pharmacology; Glia - Physiology & Pathophysiology; Molecular and Cellular Biology; Neurobiology; Neurodevelopmental Disorders; Neuroscience
Professional Summary:
My research focuses on how prenatal environmental factors such as prenatal ethanol exposure and prenatal stress exposure alter various brain functions leading to persistent cognitive and behavioral deficits (e.g. impaired executive function, increased addiction risk, and anxiety) later in life. We also study how postnatal environment can ameliorate or further exacerbate these deficits. A new focused area is the contribution of neuroinflammation in ethanol exposure-induced cellular and behavioral effects. A wide array of techniques is used in my research, including cellular/system electrophysiology, immunocytochemistry, and various behavioral techniques coupled with optogenetic and fiber photometry approaches. These techniques allow us to investigate changes in brain functions at cellular, circuitry, and behavioral levels. Our major discovery is that prenatal ethanol or prenatal stress exposure leads to over-excitation of dopamine (DA) neurons located in the ventral tegmental area (VTA) and enhance their responses to drugs of abuse resulting in increased addiction risk. In addition, we are investigating how prenatal ethanol exposure leads to cellular/molecular changes underlying impaired executive function and anxiety-like behaviors. My research contributes to the understanding of brain mechanisms mediating cognitive and behavioral deficits in fetal alcohol spectrum disorders (FASD). These findings may lead to better treatment strategies of FASD
Education and Training:
- PhD, Behavioral Neuroscience, Wayne State University (1989)
- MS, Behavioral Neuroscience, Wayne State University (1987)
- BS, Psychology, National Taiwan University (1983)
Research Expertise:
- Behavioral neuroscience, cellular and system electrophysiology,
UB 2020 Strategic Strengths:
- Health and Wellness Across the Lifespan
Grants and Sponsored Research:
- September 2022–August 2027
Role of Microglia in Prenatal ethanol exposure-induced Impairment of Endocannabinoid Signaling
NIAAA
Role: Principal Investigator - March 2021–March 2025
Synaptic transport of endocannabinoids in the brain
NIH/NIMH
Role: Co-Principal Investigator
$2,349,284 - September 2018–August 2023
Prenatal ethanol exposure and nitric oxide signaling in serotonin neurons
NIH
Role: Co-Investigator
$1,794,375 - June 2018–March 2023
Prenatal ethanol exposure on executive function
NIH
Role: Principal Investigator
$1,794,375 - February 2015–February 2022
Dopamine Function after Prenatal Ethanol Exposure
NIH/NIAAA
Role: Principal Investigator - March 2020–March 2021
Synaptic transport of endocannabinoids in the brain
NIMH/NIH
Role: Co-Principal Investigator
$679,145 - December 2010–November 2017
Addiction Propensity After Prenatal Ethanol Exposure.
NIH
Role: Principal Investigator
$1,651,617 - April 1999–March 2005
Dopamine function after prenatal ethanol exposure
NIH
Role: Principal Investigator
$1,173,418 - February 2000–February 2005
Research Training on Alcohol Etiology and Treatment
This proposal supports postdoctoral training at the Research Institute on Addictions, University at Buffalo
Role: Co-Principal Investigator - February 1997–February 2001
Chronic ethanol, dopamine electrophysiology and craving
NIH/NIAAA
Role: Principal Investigator - February 1995–February 1997
Chronic ethanol, dopamine electrophysiology and craving
NIAAA Shannon's Award
Role: Principal Investigator
Journal Articles:
- Kwarteng F, Wang R, Micov V, Hausknecht KA, Turk M, Ishiwari K, Oubraim S, Wang AL, Richards JB, Haj-Dahmane S, Shen RY. (2022) Adolescent chronic unpredictable stress leads to increased anxiety and attention deficit/hyperactivity-like symptoms in adulthood. Psychopharmacology (Dec), 239(12): 3779-3791.
- Oubraim S, Wang R, Hausknecht K, Kaczocha M, Shen RY, Haj-Dahmane S. (2022) Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats. Translational psychiatry (Oct), 12(1): 440. doi:10.1038/s41398-022-02210-7
- Wang RF, Martin CD, Lei AL, Hausknecht KA, Ishiwari K, Oubraim S, Wang AL, Richards JB, Haj-Dahmane S, Shen RY. (2022) Moderate prenatal ethanol exposure leads to attention deficits in both male and female rats. (Feb), 45: 1122-1135. doi:doi: 10.1111/ejn.14980
- 1. Oubraim SF, Wang R, Hausknecht KA, Shen RY, Haj-Dahmane S. (2022) Endocannabinoid Signaling Gates Synaptic Plasticity in Dorsal Raphe Nucleus Serotonin Neurons Through Peroxisome Proliferator-Activated Receptors. (Feb), 12: 691219.
- Ruixiang Wang, PhD; Connor D. Martin, MA; Anna L. Lei, BS; Kathryn A. Hausknecht, BA; Marisa Turk, BS; Veronika Micov, MS; Francis Kwarteng, MS; Keita Ishiwari, PhD; Saida Oubraim, PhD; An-Li Wang, PhD; Jerry B. Richards, PhD; Samir Haj-Dahmane, PhD; Roh-Yu Shen, PhD. (2022) Prenatal Ethanol Exposure Impairs Sensory Processing and Habitation of Visual Stimuli, Effects Normalized by Postnatal Environmental Enrichment. (Feb)
- Oubraim S, Wang R, Hausknecht KA, Shen RY, Haj-Dahmane S. (2021) Tonic Endocannabinoid Signaling Gates Synaptic Plasticity in Dorsal Raphe Nucleus Serotonin Neurons Through Peroxisome Proliferator-Activated Receptors. Frontiers in pharmacology (Jan), 12: 691219. doi:10.3389/fphar.2021.691219
- 5. Aghaie C IM, Hausknecht K A, Wang RF, Halaji Dezfuli P, Haj-Dahmane S, Kane C J M, Sigurdson W J, Shen, R. (2020) Prenatal ethanol exposure and environmental enrichment alter dopaminergic neuron and microglia morphology in the ventral tegmental area during adulthood. Alcoholism: Clinical and Experimental Research. Alcohol Clin Exp Res. (Feb), 44(2): 435-444. doi:doi.org/10.1111/acer.14275
- 4. Wang RF, Hausknecht KA, Gancarz-Kausch AM, Oubraim SF, Shen RY, Haj-Dahmane S. (2020) Cocaine self-administration abolishes endocannabinoid-mediated long-term depression of glutamatergic synapses in the ventral tegmental area. (Feb), 52: 4517-4524. doi:10.1111/ejn.14980
- Wang RF, Martin C D, Lei A L, Hausknecht K A, Ishiwari K, Richards J B, Haj-Dahmane S, Shen R. (2020) Prenatal ethanol exposure leads to attention deficits in both male and female rats. Frontiers in Neuroscience (Feb)(14): 12.
- Wakabayashi KTF, Feja M, Baindur AN, Bruno AN, Ghimani RV, Parl J, Hausknecht K, Shen R-Y, Haj-Dahmane S, Bass CE. (2019) Chemogenetic activation of ventral tegmental area GABA neurons, but not mesoaccumbal GABA terminals, disrupts responding to reward-predictive cues. Neuropsychopharmacology (Feb)(44): 372-380.
- Wang R, Shen YL, Hausknecht KA, Chang L, Haj-Dahmane S, Vezina P, Shen RY. (2019) Prenatal ethanol exposure increases risk of psychostimulant addiction. Behav Brain Res (Jan), 356: 51-61.
- Wang R, Hausknecht KA, Shen YL, Haj-Dahmane S, Vezina P, Shen RY. (2018) Environmental enrichment reverses increased addiction risk caused by prenatal ethanol exposure. Drug Alcohol Depend (Oct), 191: 343-347.
- Haj-Dahmane S, Shen RY, Elmes MW, Studholme K, Kanjiya MP, Bogdan D, Thanos PK, Miyauchi JT, Tsirka SE, Deutsch DG, Kaczocha M. (2018) Fatty-acid-binding protein 5 controls retrograde endocannabinoid signaling at central glutamate synapses. Proc Natl Acad Sci U S A (Jan), 115(13): 3482-3487.
- Wang R, Hausknecht KA, Haj-Dahmane S, Shen RY, Richards JB. (2018) Decreased environmental complexity during development impairs habituation of reinforcer effectiveness of sensory stimuli. Behav Brain Res (Jan), 337: 53-60.
- Hausknecht K, Shen YL, Wang RX, Haj-Dahmane S, Shen RY. (2017) Prenatal Ethanol Exposure Persistently Alters Endocannabinoid Signaling and Endocannabinoid-Mediated Excitatory Synaptic Plasticity in Ventral Tegmental Area Dopamine Neurons. J Neurosci (Jun), 37(24): 5798-5808.
- Haj-Dahmane S, Béïque JC, Shen RY. (2017) GluA2-Lacking AMPA Receptors and Nitric Oxide Signaling Gate Spike-Timing-Dependent Potentiation of Glutamate Synapses in the Dorsal Raphe Nucleus. eNeuro (May), 4(3).
- Hausknecht K, Haj-Dahmane S, Shen YL, Vezina P, Dlugos C, Shen RY. (2015) Excitatory synaptic function and plasticity is persistently altered in ventral tegmental area dopamine neurons after prenatal ethanol exposure. Neuropsychopharmacology (Mar), 40(4): 893-905.
- Hausknecht K, Haj-Dahmane S, Shen RY. (2013) Prenatal stress exposure increases the excitation of dopamine neurons in the ventral tegmental area and alters their reponses to psychostimulants. Neuropsychopharmacology (Jan), 38(2): 293-301.
- Wang J, Shen RY, Haj-Dahmane S. (2012) Endocannabinoids mediate the glucocorticoid-induced inhibition of excitatory synaptic transmission to dorsal raphe serotonin neurons. J Physiol (Nov), 590(22): 5795-5808.
- Haj-Dahmane S, Shen RY. (2011) Modulation of the serotonin system by endocannabinoid signaling. Neuropharmacology (Sep), 61(3): 414-420.
- Haj-Dahmane S, Shen RY. (2010) Regulation of plasticity of glutamate synapses by endocannabinoids and the cyclic-AMP/protein kinase A pathway in midbrain dopamine neurons. J Physiol (Jul), 588(Pt 14): 2589-2604.
- Haj-Dahmane S, Shen RY. (2009) Endocannabinoids suppress excitatory synaptic transmission to dorsal raphe serotonin neurons through the activation of presynaptic CB1 receptors. J Pharmacol Exp Ther (Oct), 331(1): 186-196.
- Muschamp JW, Dominguez JM, Sato SM, Shen RY, Hull EM, Shen R. (2007) A role for hypocretin (orexin) in male sexual behavior. J Neurosci (Mar), 27(11): 2837-2845.
- Aman TK, Shen RY, Haj-Dahmane S. (2007) D2-like dopamine receptors depolarize dorsal raphe serotonin neurons through the activation of nonselective cationic conductance. J Pharmacol Exp Ther (Jan), 320(1): 376-385.
- Shen RY, Choong KC, Thompson AC, Shen R. (2007) Long-term reduction in ventral tegmental area dopamine neuron population activity following repeated stimulant or ethanol treatment. Biol Psychiatry (Jan), 61(1): 93-100.
- Wang J, Haj-Dahmane S, Shen RY. (2006) Effects of prenatal ethanol exposure on the excitability of ventral tegmental area dopamine neurons in vitro. J Pharmacol Exp Ther (Nov), 319(2): 857-863.
- Shen RY, Choong KC, Shen R. (2006) Different adaptations in ventral tegmental area dopamine neurons in control and ethanol exposed rats after methylphenidate treatment. Biol Psychiatry (Apr), 59(7): 635-642.
- Hausknecht KA, Acheson A, Farrar AM, Kieres AK, Shen RY, Richards JB, Sabol KE, Shen R. (2005) Prenatal alcohol exposure causes attention deficits in male rats. Behav Neurosci (Feb), 119(1): 302-310.
- Haj-Dahmane S, Shen RY. (2005) The wake-promoting peptide orexin-B inhibits glutamatergic transmission to dorsal raphe nucleus serotonin neurons through retrograde endocannabinoid signaling. J Neurosci (Jan), 25(4): 896-905.
- Choong KC, Shen RY, Shen R. (2004) Methylphenidate restores ventral tegmental area dopamine neuron activity in prenatal ethanol-exposed rats by augmenting dopamine neurotransmission. J Pharmacol Exp Ther (May), 309(2): 444-451.
- Choong K, Shen R. (2004) Prenatal ethanol exposure alters the postnatal development of the spontaneous electrical activity of dopamine neurons in the ventral tegmental area. Neuroscience (Jan), 126(4): 1083-1091.
- Shen RY, Shen R. (2003) Ethanol withdrawal reduces the number of spontaneously active ventral tegmental area dopamine neurons in conscious animals. J Pharmacol Exp Ther (Nov), 307(2): 566-572.
- Xu C, Shen RY, Shen R. (2001) Amphetamine normalizes the electrical activity of dopamine neurons in the ventral tegmental area following prenatal ethanol exposure. J Pharmacol Exp Ther (May), 297(2): 746-752.
- Shen RY, Hannigan JH, Kapatos G, Shen R. (1999) Prenatal ethanol reduces the activity of adult midbrain dopamine neurons. Alcohol Clin Exp Res (Nov), 23(11): 1801-1807.
- Shen RY, Andrade R, Shen R. (1998) 5-Hydroxytryptamine2 receptor facilitates GABAergic neurotransmission in rat hippocampus. J Pharmacol Exp Ther (May), 285(2): 805-812.
- Shen RY, Hannigan JH, Chiodo LA. (1995) The effects of chronic amphetamine treatment on prenatal ethanol-induced changes in dopamine receptor function: electrophysiological findings. J Pharmacol Exp Ther (Sep), 274(3): 1054-1060.
- Shen RY, Altar CA, Chiodo LA, Shen R. (1994) Brain-derived neurotrophic factor increases the electrical activity of pars compacta dopamine neurons in vivo. Proc Natl Acad Sci U S A (Sep), 91(19): 8920-8924.
- Liu L, Shen RY, Kapatos G, Chiodo LA, Shen R. (1994) Dopamine neuron membrane physiology: characterization of the transient outward current (IA) and demonstration of a common signal transduction pathway for IA and IK. Synapse (Aug), 17(4): 230-240.
- Shen RY, Chiodo LA, Shen R. (1993) The effects of in utero ethanol administration on the electrophysiological activity of rat nigrostriatal dopaminergic neurons. Brain Res (Oct), 624(1-2): 216-222.
- Shen RY, Chiodo LA, Shen R. (1993) Acute withdrawal after repeated ethanol treatment reduces the number of spontaneously active dopaminergic neurons in the ventral tegmental area. Brain Res (Sep), 622(1-2): 289-293.
- Shen RY, Asdourian D, Chiodo LA, Shen R. (1992) Microiontophoretic studies of the effects of D-1 and D-2 receptor agonists on type I caudate nucleus neurons: lack of synergistic interaction. Synapse (Aug), 11(4): 319-329.
- Pitts DK, Kelland MD, Shen RY, Freeman AS, Chiodo LA, Shen R. (1990) Statistical analysis of dose-response curves in extracellular electrophysiological studies of single neurons. Synapse (Jan), 5(4): 281-293.
Presentations:
- "Prenatal ethanol exposure leads to failure of synaptic maturation and persistent cognitive/behavioral deficits" Gordon Conference: Alcohol & the Nervous System, Galveston, TX, March 1-6, 2020 (2020)
- "Prenatal ethanol exposure leads to persistent cognitive and behavioral deficits - rescued by environmental enrichment" Perinatal Origins of Neuropsychiatric Disorders: from Molecular Mechanisms to Therapeutic perspectives (2019)
- "Ethanol exposure alters how brain reward pathway respond to inputs and drugs" Gordon Conference: Alcohol & the Nervous System, Galveston, TX, invited speaker, 2016. (2016)
- "Prenatal ethanol exposure persistently increases glutamate synaptic transmission in ventral tegmental area dopamine neurons" Research Society on Alcoholism Symposium, invited speaker (2011)
- "Neuronal mechanisms of drug relapse" Erie County Council for the Prevention of Alcohol and Substance Abuse, Buffalo, NY, 2010 (2010)
- "The effects of chronic alcohol exposure on brain dopamine system, Canisius College, Buffalo" Canisius College, Buffalo, NY, 2000 (2000)
- "Persistent over-excitation of ventral tegmental area dopamine neurons as a critical cellular mechanism for addiction" National Taiwan University, Taipei, Taiwan (1997)
- "Brain derived neurotrophic factor increases the electrophysiological activity of substantia nigra dopamine neurons in vivo" Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 1993 (1993)
- "The effects of prenatal and postnatal alcohol exposure on the activity of dopamine neurons - possible mechanisms of craving" Department of Psychology, National Taiwan University, Taipei, Taiwan (1993)
- "The role of D-1 and D-2 dopamine receptors in regulating the glutamate-evoked activities of caudate neurons in the rat" Department of Psychology, National Taiwan University, Taipei, Taiwan (1990)
- "Does increased excitatory synaptic strength in midbrain dopamine neurons mediate enhanced addiction risk?" Department of Pharmacology and Toxicology, University at Buffalo, 2013
- "Persistent changes in the activity and synaptic transmission of midbrain dopamine neurons after prenatal ethanol exposure and the functional implications" ” SUNY Upstate NEUROFEST, Syracuse, NY, 2010
- "Prenatal ethanol exposure Leads to allostatic regulation of midbrain dopamine neurons: possible cellular mechanism for increased addiction risk" SUNY at Binghamton, NY, 2014
- "Prenatal ethanol exposure persistently impairs attention and long-term depression at glutamate synapses in the medial prefrontal cortex: effects rescued by environmental enrichment" Research Society on Alcoholism Symposium
- "The effect of fetal alcohol exposure on the activity of midbrain dopamine neurons” Department of Pharmaceutical Sciences" Department of Pharmaceutical Sciences, Department of Psychology, the Neuroscience Program, University at Buffalo, 2006
Service Activities:
- Bring Kids to Work Day; Host research activities for kids (2022)
- Frontier in Immunology (2021–2022)
- Inviting guest speaker Dr. Kristin Hamre (2021–2022)
- Texas Research Society on Alcoholism; Reviewer (2021–present)
- ACER (2021–present)
- NIH/NIAAA; The Neurotoxicology and Alcohol Study Section (NAL);; Reviewer (2020–2024)
- Behavioral Brain Research (2020–2022)
- ; Behavioral research Methods (2020–2022)
- Journal of Neuroscience Research (2020–2022)
- Undergraduate committee; Committee member (2020–present)
- PhD Program in Basic Science (PPBS) Admissions Committee as representative for the Neuroscience Program, Jacobs School of Medicine and Biomedical Sciences, UB. Serving as a secondary member in year 2018-2019. Primary member 2019-present.; Reviewer of student applications. (2018–present)
- NIH ZAA1 CC NIAAA center grant (2018–present)
- NIH Neurotoxicology and Alcohol (2018–present)
- NSERC Canada. Government of Canada. Discovery Grants program; Reviewer (2018–present)
- Neurobiology of Motivated Behavior Study Section (NMB);; Reviewer (2017–present)
- NIH Alcohol and Motivational Behavior; Ad hoc reviewer (2016–present)
- NIH Collaborative Partnership on Alcohol and Heath, RG1 IFCN-C (03); Grant reviewer (2015–present)
- NIH Disparity Research Center (ADHRC) (U54) review, ZAA1 DD (54)1; Reviewer (2015–present)
- UB/RIA Undergraduate Course Committee; Member (2015–2022)
- SUNY Brain Network of Excellence Review; Reviewer (2014–2022)
- NIH Alcohol and Reward Committee, electronic review: ZRG1 IFCN-C; Ad hoc (2013–present)
- UB/RIA Self-Study Committee 2011; Member (2011–present)
- UB/RIA Director Search Committee; Member (2011–present)
- Westminster Presbyterian Church, Buffalo, NY; Church Deacon (2010–2016)
- Erie County Council for the Prevention of Alcohol & Substance Abuse. Participated in Organizational Committee of training practitioners to recognize fetal alcohol spectrum disorder; Gave talk to inform public about Fetal Alcohol Spectrum Disorders.; Committee member (2010–2012)
- Welcome Trust Grant Review; Reviewer (2010–present)
- Westminster Presbyterian Church, Buffalo, NY; Sunday school teacher (2003–2008)
- NIH Alcohol and Toxicology Subcommittee 3; Standing member (2000–2004)
- Responsibilities: Review IACUC animal protocols are reviewed in monthly meetings. Review protocol amendments. Conduct semiannual inspections of Laboratory Animal Facilities and Laboratories using animals at and UB are performed in RIA, Buffalo General Hospital, and Children’s Hospital. Served a total of 6 years from the period of 1999 to 2014.; IACUC member (1999–2014)
- UB/RIA Institutional Seminar Planning Committee; Planning seminars (1998–2022)
- RIA, University at Buffalo BDAA grant committee; Reviewer (1998–2018)
- Institutional Controlled Substance Committee 1; Chair (1998–2018)
- UB/RIA Health and Safety Committee; Inspecting and participating in meetings regarding.health and safety issues (1998–2018)
- Westminster Presbyterian Church Energy After School Program; Tutor (1998–2001)