At dusk, Los Angeles viewed from the high-rise laboratories at Zilka Neurogenetic Institute glows under the fading light. The city begins to soften with the haze; shining, glimmering, dancing. For most at the University of Southern California’s health science campus, it signals the end of the day. For Dr. Rey Dominguez, a postdoctoral fellow at the Chow Laboratory, it’s a special time.
While the city lights flicker outside, Dominguez fires up his own light show; leveraging laser scanning technology, applying advanced imaging techniques and electrophysiology to the field of estrogen studies.
It was ten years ago as a USC Ph.D. student at the Michel Baudry lab that Dominguez stumbled upon a mechanism that could explain how hormones impact the central nervous system; focusing his research on estrogen mediated neuroprotection – the ability of estrogen to rapidly activate pro-survival pathways involved in providing protection to the brain either before or after injury or degenerative disease.
The mechanistic model that Dominguez proposed states that β-arrestin1-dependent ERK activation is a critical mediator of estradiol-mediated neuroprotection, specifically against Middle Cerebral Artery Occlusion (MCAo) injury.
“People really didn’t know how that was happening – didn’t understand how the membrane receptor was interacting with different sorts of proteins in the cell membrane in order to activate these pathways,” Dominguez explains.
Understanding the mechanisms mediating the protection and repair or neural networks is becoming increasingly relevant and important due to the rise of age-related brain diseases and injuries in the United States.
Seeing the Light: Total Internal Reflection Fluorescence Microscopy
“Estrogen studies have largely focused on the use of biochemical and histochemical techniques to track these mechanisms,” What Dominguez has been able to do with his research is provide dramatic real-time visualizations of these mechanisms – particularly in live neurons.
The images for his study are generated by a custom-built microscope illuminated with Argon laser, then captured by an Electron Multiplying Charge Coupled Device (EMCCD) camera, a high-end ultra sensitive scientific camera.
“Access to custom high-end equipment and advance training were initially what drew me to USC from UCLA as a postdoc. But it’s the mentorship that really make my postdoc experience incredible and sustainable,” he says.
In 2013, Dominguez was the recipient of the USC Provost’s Postdoctoral Scholar Research Grant. The $25,000 award supported a recent paper in collaboration with Drs. Robert Chow, principal investigator at the Chow Laboratory at USC, and Kassandra Kisler from the Berislav Zlokovic Lab, who specializes in the study of Alzheimer’s disease through live-tissue imaging.
The paper utilized Total Internal Reflection Fluorescence Microscopy TIRFM to image the trafficking mechanism, providing further evidence that activation of estradiol receptors modulate neuronal physiology and neuroprotection in the nervous system. Additionally, the grant bridges the next steps of his study, using in vivo mouse model of global cerebral hypoperfusion and 3D image reconstruction of cortical neurons.
Video clip: 3D Imaging of Cortical Neurons
The approach to research in the published paper exemplifies a broader university initiative: promoting and facilitating collaboration and innovations between researchers of diverse and disparate disciplines.
“It’s like a salad here! Everyone has different backgrounds and areas of specialty. The advantage to that is we’re all able to talk about the techniques. This allows for more innovations and different ways to look at research,” Dominguez says.
This fall, Dominguez will be chairing a scientific symposia titled “Stayin’ Alive: Live Cell Imaging Basics for Neuroscientist” during the Society for the Advancement of Chicanos and Native Americans (SACNAS) National Conference in Los Angeles.
Read the article at USC News.