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Dr. Robert C. Malenka is the Pritzker Professor of Psychiatry and Behavioral Sciences, Director of the Nancy Pritzker Laboratory and Deputy Director of the Wu Tsai Neurosciences Institute. After graduating from Harvard College he received an M.D. and a Ph.D. in neuroscience in 1983 from Stanford University School of Medicine. Over the ensuing 6 years he completed residency training in psychiatry at Stanford and 4 years of postdoctoral research at the University of California, San Francisco (UCSF). In 1989, he was appointed Assistant Professor of Psychiatry and Physiology at UCSF, at which he reached the rank of Full Professor in 1996. In addition to running an active research program at UCSF he was the Director of the Center for the Neurobiology of Addiction and Associate Director of the Center for Neurobiology and Psychiatry. He returned to the Stanford University School of Medicine in 1999. He is an elected member of the National Academy of Sciences and the National Academy of Medicine as well as an elected fellow of the American Academy of Arts and Sciences, the American Association for the Advancement of Science, and the American College of Neuropsychopharmacology. He has served on the National Advisory Council on Drug Abuse and as a Councilor for the Society for Neuroscience and the American College of Neuropsychopharmacology. He is on the scientific advisory boards of numerous non-profit foundations and biotechs. He has been the recipient of several awards including: the Society for Neuroscience Young Investigator Award (1993); the Daniel Efron Award from the American College of Neuropsychopharmacolgoy (1998); the Kemali Foundation International Prize in Neuroscience (2000); the CINP-Lilly Neuroscience Basic Research Award (2002), the Perl/UNC Neuroscience Prize (2006), the NARSAD Goldman-Rakic Prize for Outstanding Neuroscience Research (2010), the Pasarow Foundation Award for Extraordinary Accomplishment in Neuropsychiatry Research (2011), and the Society for Neuroscience Julius Axelrod Prize (2016). His laboratory continues to conduct research on the molecular mechanisms of neural communication as well as the role of circuit dysfunction in brain disorders including addiction, Alzheimer’s, autism, and depression.
Long-lasting activity-dependent changes in the efficacy of synaptic transmission play an important role in the development of neural circuits and may mediate many forms of learning and memory. Work from my laboratory over the last 10 years has demonstrated that there are a variety of related but mechanistically distinct forms of synaptic plasticity. A major goal of my laboratory is to elucidate both the specific molecular events that are responsible for the triggering of these various forms of synaptic plasticity and the exact modifications in synaptic proteins that are responsible for the observed, long-lasting changes in synaptic efficacy. To accomplish this we use cellular electrophysiological recording techniques to examine synaptic plasticity in a variety of different in vitro preparations including thin slices of various regions of the rodent brain and primary neurons in culture. We also use cell biological and molecular techniques to examine the activity-dependent modulation of neurotransmitter receptors and to express dominant negative forms of various synaptic proteins so that their exact functions can be determined. An additional complementary approach has involved examining synaptic physiology and synaptic plasticity in various mutant mouse lines lacking specific synaptic proteins.<br/><br/>A related but independent area of research in my laboratory is the elucidation of the synaptic action of drugs of abuse such as the psychostimulants cocaine and amphetamine. Toward this end, we have developed in vitro slice preparations of the nucleus accumbens and ventral tegmental area, brain regions which are thought to mediate several of the behavioral effects of drugs of abuse. We have characterized a novel form of synaptic plasticity in the nucleus accumbens and have done an extensive pharmacological characterization of the synaptic effects of dopamine, cocaine, and amphetamine. Currently we are examining in more detail the underlying mechanisms of dopamine's actions and determining how chronic treatment with drugs of abuse affect the synaptic responses of nucleus accumbens and ventral tegmental area cells. Because chronic exposure to drugs of abuse elicit long-term adaptive changes in critical neural circuits, it is hoped that the knowledge gained from the work on the molecular mechanisms underlying synaptic plasticity will provide important clues to the molecular mechanisms underlying the development of tolerance, dependence and addiction.
Engaging Self-regulation Targets to Improve Mood and Weight and Understand Mechanism in Depressed and Obese Adults
Multimorbidity (i.e., the coexistence of 2 or more chronic conditions in an individual) is
increasingly recognized as a pressing public health problem. Effective interventions
targeting coexisting depression and obesity are critical given the high prevalence and
worsened outcomes for patients with both conditions.
ENGAGE-2 is a pilot randomized controlled trial (RCT). The objective is to investigate the
outcomes and mechanisms of an integrated depression and obesity intervention that combines
collaborative stepped depression treatment and evidence-based behavioral weight loss
treatment. The Integrated Coaching for Better Mood and Weight-2 (I-CARE2) intervention
synergistically integrates 2 proven national programs: the Program to Encourage Active and
Rewarding Lives (PEARLS) for depression care and the Group Lifestyle Balance (GLB) program
for weight loss and cardiometabolic risk reduction.
In Phase 1 of the ENGAGE project, investigators developed a new protocol to quantify
activation and connectivity of the Affective, Cognitive Control, and Default Mode brain
circuits from functional magnetic resonance imaging (fMRI) among 108 depressed obese
patients. Investigators implement the same fMRI protocol in this second phase of the project
to examine the mechanistic role of these brain circuits as potential neural targets in
treatment engagement and response in the I-CARE2 intervention. A new sample of 105 depressed
obese patients are randomized in a 2:1 ratio to receive the I-CARE2 intervention (n=70) or
usual care (n=35). Study assessments occur at 0 (baseline), 2 and 6 months. Investigators
hypothesize that 1 or more of the neural targets under study will moderate (baseline state)
and/or mediate (change at follow-up) the effect of the I-CARE2 intervention versus usual care
on health behaviors (problem-solving ability, dietary intakes, physical activity) and
clinical outcomes (weight loss, depression, anxiety).
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