Due to COVID-19, I had to deliver the Robbins Distinguished Educator Award Lecture via Zoom.
While it was odd not being able to have eye contact with attendees, I am happy that at least some of my messages directed at trainees seem to have been heard.
In the talk, I discussed unexpected findings for the PINK1 field of recessive Parkinson's disease, including the fact that knockout mice do not show overt neurodegeneration. This was followed by our published and unpublished data supporting the hypothesis that autophagy/mitophagy upregulation compensates for PINK1 loss in culture and in vivo. The next unexpected finding was that PINK1-deficient neurons are nevertheless fully capable of upregulating compensatory mitophagy, which led to a major basic science discovery of the cardiolipin pathway of mitophagy cargo specification as reported in Nature Cell Biology and Cell Death and Differentiation. To understand neuron-specialized roles for PINK1, we embarked on immunoprecipitation-mass spectrometry studies that led to the discovery the PINK1 plays a crucial role in dendritic arborization, interacting with valosin-containing protein and protein kinase A to phosphorylate p47, published in the open access SFN journal eNeuro. Delving further into mechanisms that regulate PINK1 proteasomal degradation resulted in a pair of studies published in Journal of Biological Chemistry and JCI Insight. Assisted by our IP-MS data and computational modeling, we identified one of the first small molecules capable of protecting not only against cell death, but also dendritic retraction/simplification elicited by acute parkinsonian intoxication.
As trainees often struggle with the ups and downs of science, I wanted to close by offering some advice for getting the most out of this lifelong journey of discovery. Students sometimes feel discouraged when asked to go delve deeper, move faster, convince skeptics, or reanalyze data when potential flaws are pointed out. Yet science is a lifelong quest for learning, discovery and improvement, even for full professors. Remember, busy people wouldn't care to take the time to offer constructive critiques if they did not believe in you.
For those that were unable to attend the webinar, here is the final slide.