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​Mind the Gap: Dr. Bruce J. Nicholson

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Author: MaryAnn Hobbs | Category: Faculty Spotlight | Molecular Biophysics & Biochemistry(MBB) | Molecular Biophysics and Biochemistry | July 18, 2017

Dr. Bruce J. Nicholson was born and raised in Australia, where he stayed until his journey through academia took him coast to coast in America. Although he now resides in Texas as a professor and chair of the Department of Biochemistry at UT Health San Antonio, he began his academic journey at the University of Queensland. While in Australia, Dr. Nicholson studied biochemistry, but it was his love for neuroscience that led him across the pond to California to pursue his Ph.D.

There were quite a few speed bumps on the road to America. For most students, the hard part of going to graduate school is finding a school that they like, and being accepted by that school. For Dr. Nicholson this was not the case. When applying to graduate programs that interested him, he passed the acceptance criteria at The University of California, Los Angeles (UCLA) and The University of California at San Francisco (UCSF), but the schools did not provide any financial aid to international students. Another professor that he directly reached out to at Harvard welcomed Nicholson to his lab, but he informed Dr. Nicholson that he was moving to UCSF, the school he had already been told could provide no aid!

After hearing from his brother—an an astrophysicist then at the California Institute of Technology or Caltech—that his school might have, “a decent Biology Department,” that became his final choice for pursuing his doctorate in neuroscience. “I liked molecular neuroscience because it was a new enough field, at the time, that there was room to grow,” but still enough information to see the potential of the specialty. Dr. Nicholson explained that it was really the chemistry of biological processes that interested him, which is how he utilized his biochemistry background to break into the field of neuroscience.

The bumps on the road to graduate school turned into mountains once it was time for Dr. Nicholson to find a mentor to do his Ph.D.

“I always tell graduate students not to worry too much about who their mentor is going to be, I got my fifth choice, and it worked out pretty well for me” he said. 

After trying a faculty member who had not yet set up his lab, another who was denied tenure and leaving, and yet another who proved to have a difficult personality, the principle investigator of the last lab that seemed to be perfect, drowned the weekend before Dr. Nicholson was to interview with him. 

This left Dr. Nicholson to his fifth choice professor, Dr. Jean-Paul Revel, the man who ultimately became his mentor and the person to shift his attention from traditional chemical synapses to the electrical synapses of gap junctions—a field he still currently studies here at UT Health San Antonio.

After doing a postdoc with Dr. Norman Davidson, also at Caltech, Dr. Nicholson’s first job in academia was at The University at Buffalo in New York as an assistant professor. “Must have been a good fit,” he said, “I was offered a job a week after interviewing, and stayed for 17 years.” But after seeing only the top of car antennas in parking lots after yet another heavy snow, Dr. Nicholson warmed up to the idea of coming to UT Health San Antonio, where he has happily stayed for the last 13 years as Chairman of Biochemistry.

Research

Today, Dr. Nicholson studies gap junctions, which are channels on the plasma membrane that allow cells to communicate with each other, by mediating the passage of ions and small molecules directly from cell to cell. He explained that: “Gap junctions are present throughout your body in almost every cell,” and their high prevalence can be used as opportunity to understand, and combat, many different and seemingly unrelated diseases. We just have to learn the “language of their communication.”

He has found that not all gap junctions are created equal, and channels are specific for what metabolites they allow through; meaning different gap junctions cause different metabolic communication between cells.

Dr. Nicholson mentioned that, “Studying the movement of the metabolites can be quite difficult, since metabolites have an annoying habit of metabolizing, or degrading in cells, so one of the challenges we face is slowing their metabolism so we know what is actually passing through the gap junction channels. Understanding the language of intercellular communication of the different gap junctions could lead to finding new therapeutic strategies.”

Mutations of gap junctions lead to many different diseases, such as hearing loss (where they are the most common cause of genetically inherited deafness), various skin diseases (e.g.. Vohwinkel and keratitis–ichthyosis syndromes), cataracts, cardiac arrhythmias and limb paralysis due to demyelination. Dr. Nicholson’s lab has investigated functions of some of the mutants that cause deafness and skin disease, which may help guide development of drugs that could ameliorate diseases.

Dr. Nicholson also explained how gap junctions could also provide insights into what processes underlie the unregulated growth of cancer cells. His lab expressed different gap junction proteins in a human tumor cell line, and found that only one suppressed tumor cell growth patterns. This was found to be due to metabolite redistribution. This finally explained the 50-year mystery of how gap junction communication among identical cells could inhibit their growth.

He believes that by understanding the mechanism by which our cells communicate with each other, it may help us uncover the key to helping many different diseases. “Biochemistry helps to unveil what is going on in the cell at the molecular level, and with that information scientists and medical professionals can further transform that into treatments,” he said.

Advice

Dr. Nicholson ended with a few words of wisdom. First he said, “Never just compare yourself to the students around you. You may be doing well in your classes here so you think you can go out every weekend, but that student at Harvard with a higher GPA than you is probably staying in to study and work in the lab nights and weekends, and that Harvard student is competing for the same jobs you are.”

He went on to tell his favorite quote that a teacher had told him was: “You can make any mistake once, and that’s fine, but if you make the same mistake a second time you are either stupid or not thinking,” which Dr. Nicholson has taken with him throughout his endeavors and passed on along the way.

When asked how one should choose which discipline of science to go into, he said, “That depends on at what level you are content with answering the question.” He explained that, for example, pharmacology might answer the question of how a drug improves or affects a disease at the organ or whole body level, while a biochemist might answer the question of what residues on what proteins interact with the drug, so its mode of action can be understood and improved. “It is easier to think of what questions the different disciplines are answering and how they ask it, and then fit that with how you want to answer questions.”

“But the most important thing” Dr. Nicholson stressed, “is not to let your love of science consume you, but stay involved with your family’s lives.” He said that he feels thankful that no matter how busy he was through teaching and research, his wife ensured that he took the time to develop a relationship with his daughters, who still call him daily. Now that his daughters are grown, Dr. Nicholson dedicates spending time with his wife of 37 years, and with each and every one of his six cats, who themselves have been published (in a local magazine)! 

About the Author 

MaryAnn is currently a research assistant in the Cellular and Integrative Physiology department, with hopes of attending a Biochemistry and Structural Biology graduate program in fall 2018.



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