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Dopamine researcher investigating the underlying mechanism of addiction and depression wins 2019 ASPET Division of Neuropharmacology Early Career Investigator Award

April 09, 2019
By Sean P Moran, Neuroscience PhD Candidate, Vanderbilt University, Nashville TN

NEU_EarlyCareer_Mazei-RobinsonASPET’s Division of Neuropharmacology is excited to present Dr. Michelle Mazei-Robison with the 2019 Early Career Investigator Award. As a promising young faculty member at Michigan State University, Dr. Mazei-Robison has already made significant contributions to the field of opiate addiction and psychiatric illnesses. Her research has contributed to the characterization of genetic variants to the dopamine transporter found in patients with ADHD and how these variants drive dopamine efflux, how chronic exposure to opiates can induce morphological changes to dopamine neurons, and the circuit-specific morphological changes to dopamine neurons after chronic opiate exposure. Overall, these studies have greatly added to our collective knowledge of the dopamine system and how genetic variants or chronic exposure to opiates can induce dramatic changes in the brain.

Dr. Mazei-Robison has a long record of investigating the underlying mechanisms driving addiction behavior, beginning with her undergraduate research at Central Michigan University. During this time, she realized the power of genetics and molecular biology to understand and characterize the nervous system. Therefore, after graduation she joined Randy Blakely’s lab at Vanderbilt University to study the effects of coding variants on the dopamine transporter, DAT. Here, she identified novel mutations in the gene encoding DAT in children with ADHD, and investigated their influence on transporter function. Specifically, this rare coding variant in DAT did not change DAT protein expression nor dopamine uptake, but caused anomalous dopamine efflux from dopamine containing cells. This research, yielding several publications, shed light on how rare coding variants in the dopamine receptor can lead to dramatic changes in the dopamine system and underlie the altered dopamine signaling in disorders such as ADHD. Always forward thinking, Dr. Mazei-Robison’s goal for the next chapter of her career was to combine her genetics and molecular skills with her previous training in animal behavior.

Committed to the goal of becoming an independent researcher, she then joined Eric Nestler’s lab in order to combine genetics, molecular biology and rodent behavior to better understand the dopamine system. Here, she was on the cutting edge of investigating the devastating effects opiates can have on behavior well before opiate addiction received the national attention it deserved. Throughout her extremely productive post-doc with the Nestler lab, her neuropharmacology research studying the effects of opiates on addiction was truly pioneering since much of the addiction field was focused on cocaine and alcohol addiction. Here she demonstrated that the mammalian target of rapamycin complex-2 in the ventral tegmental area (VTA), an important source of dopamine neurons in the brain, is critical for the rewarding effects of morphine. She then demonstrated that overexpression of Rictor, a component of mTORC2, prevents morphine-induced changes in cell morphology and activity. Additionally, local knockout of Rictor in the VTA decreases dopamine neuron soma size and reduces rewarding responses to morphine. These studies helped elucidate the signaling pathways critical for mediating neuroadaptations to opiates of abuse. When asked what it was like to see the field of opiate addiction expand exponentially over the last few years, she said it was “really exciting to see the field grow in order to better understand this epidemic.”

After returning back to Michigan to start her own lab at Michigan State University, Dr. Mazei-Robison’s research continues to focus on the dopamine system with emphasis on addiction and depression. When asked about how she manages her own lab, she currently, “tries to recapitulate the beneficial aspects of a large lab, while focusing on the more one-on-one training found in smaller labs,” and runs her lab based on two philosophies.  The first, is that her last two mentors provided a significant amount of independence that allowed her to quickly grow as an independent scientist and learn how to drive projects forward. Second, her previous training environments emphasized a high degree of collaboration. The former philosophy provided the training necessary to become an independent researcher and the latter has allowed her to move projects forward at an impressive pace. She contributes her success to her previous mentors emphasizing “thinking independently and collaborating with many scientists,” since many of the questions she is passionate about answering need a breadth of techniques that are hard to accomplish by a single person in a short amount of time.
Dr. Mazei-Robison’s Lab

While her lab at Michigan State University primarily consists of graduate and undergraduate students, she nonetheless works towards instilling a large degree of independence with her students in order to prepare them with skills that will be useful for their next career stage in science. Additionally, she emphasizes a high degree of collaboration between members of her lab as well as collaboration with outside experts, reflecting the need of multiple specialties/expertise to answer the important unanswered questions in science. Lastly, like many younger faculty members, she admits to spending less and less time at the bench but still prioritizes hands on training with her students, relishing the opportunity to get back to the bench from time-to-time.

Outside the lab, her and her husband (who is also a professor at Michigan State University) love to cook with their children and plan out the best places to eat when traveling for invited talks and conferences.

The 2019 Early Career Investigator Award was presented to and Dr. Mazei-Robison presented a lecture titled “Novel Molecular Mechanisms Induced in the Ventral Tegmental Area by Drugs of Abuse” during the ASPET Annual Meeting at EB 2019 in Orlando, FL in the division’s award platform session on Monday, April 8, 2019.

If you would like to contribute to this blog, please contact Luisa at lft9@cornell.edu.
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