“I have worked with Billy on a project involving International Business Methodologies. Billy is an intelligent scientist with a good blend of hard core science understanding and very real world business acumen. He gained concepts of business very fast and asked insightful questions in the class. He is an excellent team player and completed assigned tasks on time. He is diligent and very hardworking. It was a pleasure working with him and I recommend Billy for all his professional qualities that make him an asset on any life science consulting type, project management and product development roles.”
About
Innovative scientist with graduate-level business training and professional consulting…
Activity
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Congrats to GH's teams to advance one step further to expand precision medicine applications in the Japanese and Asia markets. On the other hand…
Congrats to GH's teams to advance one step further to expand precision medicine applications in the Japanese and Asia markets. On the other hand…
Liked by Billy Chen, Ph.D.
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Four years ago, I started a podcast out of my garage. I wanted to explore where a career in science can take you, hopefully to inspire the next…
Four years ago, I started a podcast out of my garage. I wanted to explore where a career in science can take you, hopefully to inspire the next…
Liked by Billy Chen, Ph.D.
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In a development that could help address the colorectal cancer screening gap, an FDA panel of experts recently recommended the approval of Shield…
In a development that could help address the colorectal cancer screening gap, an FDA panel of experts recently recommended the approval of Shield…
Liked by Billy Chen, Ph.D.
Experience & Education
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Guardant Health
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Licenses & Certifications
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Certificate of Achievement-Alliance Management (CA-AM)
Association of Strategic Alliance Professionals
Issued
Publications
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The Mesocortical Dopamine System
The Human Frontal Lobes, Third Edition
A book chapter in Miller, B.L. & Cummings, J.L. (Eds.), The Human Frontal Lobes, Third Edition. (pp 29-41). New York, NY: Guilford Press
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Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking
Nature
Corresponding author (Publication date: April 11, 2013)
A study using compulsive drug-seeking behavior reveals that prolonged cocaine self-administration decreases prelimbic cortex activity resulting in increased compulsive drug seeking; importantly, increasing activity in the prelimbic cortex decreases compulsive drug-seeking behaviors. Finding demonstrates targeted stimulation of prefrontal cortex could serve as a promising therapy for treating compulsive drug use.
NIDA press release:…Corresponding author (Publication date: April 11, 2013)
A study using compulsive drug-seeking behavior reveals that prolonged cocaine self-administration decreases prelimbic cortex activity resulting in increased compulsive drug seeking; importantly, increasing activity in the prelimbic cortex decreases compulsive drug-seeking behaviors. Finding demonstrates targeted stimulation of prefrontal cortex could serve as a promising therapy for treating compulsive drug use.
NIDA press release: http://www.drugabuse.gov/news-events/news-releases/2013/04/nih-study-sheds-light-how-to-reset-addicted-brain
UCSF press release: http://www.ucsf.edu/news/2013/04/104831/laser-light-zaps-away-cocaine-addictionOther authors -
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Differential calcium dependence of axonal versus somatodendritic dopamine release, with characteristics of both in the ventral tegmental area.
Frontiers in Systems Neuroscience
Midbrain dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) exhibit somatodendritic release of DA. Previous studies indicate a difference between the Ca2+ dependence of somatodendritic DA release in the SNc and that of axonal DA release in dorsal striatum. Here, we evaluated the Ca2+ dependence of DA release in the VTA and nucleus accumbens (NAc) shell for comparison with that in the SNc and dorsal striatum. Release of DA was elicited by…
Midbrain dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) exhibit somatodendritic release of DA. Previous studies indicate a difference between the Ca2+ dependence of somatodendritic DA release in the SNc and that of axonal DA release in dorsal striatum. Here, we evaluated the Ca2+ dependence of DA release in the VTA and nucleus accumbens (NAc) shell for comparison with that in the SNc and dorsal striatum. Release of DA was elicited by single-pulse stimulation in guinea-pig brain slices and monitored with subsecond resolution using carbon-fiber microelectrodes and fast-scan cyclic voltammetry. In dorsal striatum and NAc, DA release was not detectable at extracellular Ca2+ concentrations ([Ca2+]o) below 1 mM; however, a progressive increase in evoked extracellular DA concentration ([DA]o) was seen with [Ca2+]o ≥ 1.5 mM. By contrast, in SNc and VTA, robust increases in [DA]o could be elicited in 0.25 mM [Ca2+]o that were ∼60% of those seen in 1.5 mM [Ca2+]o. In SNc, a plateau in single-pulse evoked [DA]o was seen at [Ca2+]o ≥ 1.5 mM, mirroring the release plateau reported previously for pulse-train stimulation in SNc. In VTA, however, evoked [DA]o increased progressively throughout the range of [Ca2+]o tested (up to 3.0 mM). These functional data are consistent with the microanatomy of the VTA, which includes DA axon collaterals as well as DA somata and dendrites. Differences between axonal and somatodendritic release data were quantified using Hill analysis, which showed that the Ca2+ dependence of axonal DA release is low affinity with high Ca2+ cooperativity, whereas somatodendritic release is high affinity with low cooperativity. Moreover, this analysis revealed the dual nature of DA release in the VTA, with both somatodendritic and axonal contributions.
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AMPA receptor synaptic plasticity induced by psychostimulants: the past, present, and therapeutic future.
Neuron
Experience-dependent plasticity at excitatory synapses of the mesocorticolimbic system is a fundamental brain mechanism that enables adaptation to an ever-changing environment. These synaptic responses are critical for the planning and execution of adaptive behaviors that maximize survival. The mesocorticolimbic system mediates procurement of positive reinforcers such as food and sex; however, drugs of abuse re-sculpt this crucial circuitry to promote compulsive drug-seeking behavior. This…
Experience-dependent plasticity at excitatory synapses of the mesocorticolimbic system is a fundamental brain mechanism that enables adaptation to an ever-changing environment. These synaptic responses are critical for the planning and execution of adaptive behaviors that maximize survival. The mesocorticolimbic system mediates procurement of positive reinforcers such as food and sex; however, drugs of abuse re-sculpt this crucial circuitry to promote compulsive drug-seeking behavior. This review will discuss the long-term changes in glutamatergic neurotransmission that occur within the mesolimbic system following cocaine exposure. In addition, we will examine how these long-lasting neuroadaptations may drive the pathology of psychostimulant addiction. Finally, we review clinical trials that highlight antagonists at excitatory AMPA receptors as promising targets against cocaine abuse.
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Synaptic plasticity in the mesolimbic system: Therapeutic implications for substance abuse
Ann N Y Acad Sci.
In an ever-changing environment, animals must learn new behavioral strategies for the successful procurement of food, sex, and other needs. Synaptic plasticity within the mesolimbic system, a key reward circuit, affords an animal the ability to adapt and perform essential goal-directed behaviors. Ironically, drugs of abuse can also induce synaptic changes within the mesolimbic system, and such changes are hypothesized to promote deleterious drug-seeking behaviors in lieu of healthy, adaptive…
In an ever-changing environment, animals must learn new behavioral strategies for the successful procurement of food, sex, and other needs. Synaptic plasticity within the mesolimbic system, a key reward circuit, affords an animal the ability to adapt and perform essential goal-directed behaviors. Ironically, drugs of abuse can also induce synaptic changes within the mesolimbic system, and such changes are hypothesized to promote deleterious drug-seeking behaviors in lieu of healthy, adaptive behaviors. In this review, we will discuss drug-induced neuroadaptations in excitatory transmission in the ventral tegmental area and the nucleus accumbens, two critical regions of the mesolimbic system, and the possible role of dopamine receptors in the development of these neuroadaptations. In particular, we will focus our discussion on recent studies showing changes in AMPA receptor function as a common molecular target of addictive drugs, and the possible behavioral consequences of such neuroadaptations.
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Reduced nucleus accumbens SK channel activity enhances alcohol seeking during abstinence
Neuron
The cellular mechanisms underlying pathological alcohol seeking remain poorly understood. Here, we show an enhancement of nucleus accumbens (NAcb) core action potential firing ex vivo after protracted abstinence from alcohol but not sucrose self-administration. Increased firing is associated with reduced small-conductance calcium-activated potassium channels (SK) currents and decreased SK3 but not SK2 subunit protein expression. Furthermore, SK activation ex vivo produces greater firing…
The cellular mechanisms underlying pathological alcohol seeking remain poorly understood. Here, we show an enhancement of nucleus accumbens (NAcb) core action potential firing ex vivo after protracted abstinence from alcohol but not sucrose self-administration. Increased firing is associated with reduced small-conductance calcium-activated potassium channels (SK) currents and decreased SK3 but not SK2 subunit protein expression. Furthermore, SK activation ex vivo produces greater firing suppression in NAcb core neurons from alcohol- versus sucrose-abstinent rats. Accordingly, SK activation in the NAcb core significantly reduces alcohol but not sucrose seeking after abstinence. In contrast, NAcb shell and lateral dorsal striatal firing ex vivo are not altered after abstinence from alcohol, and SK activation in these regions has little effect on alcohol seeking. Thus, decreased NAcb core SK currents and increased excitability represents a critical mechanism that facilitates motivation to seek alcohol after abstinence.
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Cocaine but not natural reward self-administration nor passive cocaine infusion produces persistent LTP in the VTA
Neuron
Persistent drug-seeking behavior is hypothesized to co-opt the brain's natural reward-motivational system. Although ventral tegmental area (VTA) dopamine (DA) neurons represent a crucial component of this system, the synaptic adaptations underlying natural rewards and drug-related motivation have not been fully elucidated. Here we show that self-administration of cocaine, but not passive cocaine infusions, produced a persistent potentiation of VTA excitatory synapses, which was still present…
Persistent drug-seeking behavior is hypothesized to co-opt the brain's natural reward-motivational system. Although ventral tegmental area (VTA) dopamine (DA) neurons represent a crucial component of this system, the synaptic adaptations underlying natural rewards and drug-related motivation have not been fully elucidated. Here we show that self-administration of cocaine, but not passive cocaine infusions, produced a persistent potentiation of VTA excitatory synapses, which was still present after 3 months abstinence. Further, enhanced synaptic function in VTA was evident even after 3 weeks of extinction training. Food or sucrose self-administration induced only a transient potentiation of VTA glutamatergic signaling. Our data show that synaptic function in VTA DA neurons is readily but reversibly enhanced by natural reward-seeking behavior, while voluntary cocaine self-administration induced a persistent synaptic enhancement that is resistant to behavioral extinction. Such persistent synaptic potentiation in VTA DA neurons may represent a fundamental cellular phenomenon driving pathological drug-seeking behavior.
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Cocaine self-administration selectively abolishes LTD in the core but not shell of the nucleus accumbens.
Nature Neuroscience
The core and shell of the nucleus accumbens have critical, differential roles in drug-dependent behaviors. Here we show that operant cocaine self-administration inhibits long-term depression (LTD) in both structures after 1 d of abstinence. However, after 21 d of abstinence, LTD was abolished exclusively in the nucleus accumbens core of cocaine self-administering rats, suggesting that voluntary cocaine self-administration induced long-lasting neuroadaptations in the core that could underlie…
The core and shell of the nucleus accumbens have critical, differential roles in drug-dependent behaviors. Here we show that operant cocaine self-administration inhibits long-term depression (LTD) in both structures after 1 d of abstinence. However, after 21 d of abstinence, LTD was abolished exclusively in the nucleus accumbens core of cocaine self-administering rats, suggesting that voluntary cocaine self-administration induced long-lasting neuroadaptations in the core that could underlie drug-seeking behavior and relapse.
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Courses
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Bioscience Strategy
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Corporate Finance
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Fundamentals of Commercial Biotech Operations
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International Business and Global Health
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Introduction to U.S. Food and Drug Law
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Marketing Management
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Valuation in the Applied Life Sciences
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Honors & Awards
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Invited Speaker at NIDA/SFN Frontier in Neuroscience Symposium
National Institutes of Health / National Institute on Drug Abuse
Invited to give talk at the annual NIDA/SFN Frontier in Neuroscience Meeting at Washington, D.C. The talk focused on my current work demonstration how prolonged drug intake and compromise decision-making processes in the prelimbic area. Further, prelimbic area stimulation using state-of-the art optogenetic technology reverses compulsive drug seeking. My results indicate that targeted stimulation of the prefrontal cortex could serve as a promising therapeutic strategy for the treatment of…
Invited to give talk at the annual NIDA/SFN Frontier in Neuroscience Meeting at Washington, D.C. The talk focused on my current work demonstration how prolonged drug intake and compromise decision-making processes in the prelimbic area. Further, prelimbic area stimulation using state-of-the art optogenetic technology reverses compulsive drug seeking. My results indicate that targeted stimulation of the prefrontal cortex could serve as a promising therapeutic strategy for the treatment of compulsive behaviors.
http://www.drugabuse.gov/frontiers-in-addiction-research-mini-conventions/frontiers-in-addiction-research-2011/using-optogenetics-to-shed-light-neural
Languages
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English
Native or bilingual proficiency
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Mandarin
Professional working proficiency
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