Read our faculty interview with Dr. Benjamin Deneen

1.	Dr. Deneen is an Associate Professor at the Baylor College of Medicine

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Astrocyte Development & Function Poster

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I’m Benjamin Deneen, and this is why I research.

Benjamin Deneen trained as a postdoctoral fellow at the California Institute of Technology in the laboratory of Dr. David Anderson where he discovered the role of the transcription factor Nuclear factor IA (NFIA) in gliogenesis. In 2009, he joined the Neuroscience faculty at the Baylor College of Medicine where he is currently a Professor. His laboratory continues to elucidate the biology of glial development and the role of key gliogenic factors in neurological disease. Among their most recent findings is the identification of the role of NFIA in glioma formation and subtype generation which may provide new avenues for the treatment of malignant gliomas.

As a mentor, it’s critical to remember that your success is directly tied to their success. If you want to have a successful lab, then you have to invest in your mentee’s success and recognize that you need them as much (if not more!) than they need you.

Would you tell us what sparked your interest in science?

There is no specific moment or event that triggered my interest in science. From a young age, I’ve always been curious about the natural world and when this curiosity was converted into formal education the pursuit of knowledge via scientific investigation gradually became a part of me. Hence, I suppose the “spark” for me was really more of a process or journey.

Your early work focused on transcriptional regulators of gliogenesis, particularly the role of NFIA in this process. What are some unexpected functions of NFIA in the developing spinal cord?

When I started my lab 10 years ago, the masterplan was to use the biology surrounding NFIA as a springboard to initiate my independent career and then quickly move on to other “more exciting” pursuits. Over the past decade, we have used NFIA as a molecular entry point for understanding glial cell biology, brain tumors, and glial regeneration; I would say that these are pretty exciting pursuits! Thus, the most unexpected finding is the broad reach of NFIA biology across development and a host of neurological diseases. Currently, we are expanding our investigations on NFIA into adult brain function. Looking back 10 years, these investigations are also quite unexpected. So, please stay tuned, there is more on the way.

Recent findings from your lab have helped shape current understanding of the relation between astrocyte’s molecular and functional diversity. Is there one specific discovery that you feel most proud of? An ‘aha moment’?

The nature of astrocyte diversity is such an obvious and open question that it was simply a matter of time before someone answered it. I suppose this realization might constitute a “aha” moment. With that said, now that we have initiated these studies and have some broad parameters for their diversity it’s clear that we are merely scratching the surface and the real work is now beginning. This involves making new tools to query their diverse functions and using lessons from other cellular classification systems to further refine our methods of cataloging astrocytes. Therefore, I would venture to guess that the real “aha” moment has yet to come!

Your group’s findings on astrocyte diversity and mechanisms of OLP differentiation have important implications for cancer and neurological diseases. How do developmental and disease mechanisms compare and how does this knowledge help to create therapeutic opportunities?

Development and disease are different sides of the same coin. You cannot truly know one, without knowing the other. I view development as the blueprint for understanding disease mechanisms and an essential part of translational science. Generating rationale therapeutics can only really begin once a basic understanding of the cellular system has been achieved. For example, my lab studies the developmental mechanisms that control the generation of glial cells, with a keen eye on translation: If we can better understand how to make glial cells, then we can understand how glial cells become glioma and how to make more of them for regenerative purposes. Clearly these are two disciplines that need one another.

Dr. Deneen’s lab members at the Baylor College of Medicine

How do you balance basic and translational research pursuits in your lab?

These pursuits go hand-in-hand. Once we have identified a basic mechanism or cellular process, we immediately find ways to test whether and how it operates in a disease state, albeit cancer, degeneration, or injury. With that said, this is not a trivial task, as it requires both intellectual and experimental dexterity, and you run the risk of spreading yourself and projects too thin. In many ways, my laboratory is fortunate to be in the largest medical center in the world (Texas Medical Center), which greatly facilitates these translational endeavors through collaborations with clinicians and translational scientists. It is at the intersection of these seemingly disparate fields where true innovation lies and we are fortunate to be in a position to pursue both basic and translational questions.

Tell us more about the questions being pursued in your lab and where do you see your research moving in the near future?

Recently, my lab has taken extreme measures to initiate studies on astrocyte contributions to circuit function in the adult brain. Since I have spent most of my career trying to understand how to make astrocytes, I now want to know what they actually do and how do these functions influence brain physiology and, ultimately, our behavior. In parallel, we also want to apply these principles of glial-neuron communication to brain tumors and begin decoding the “neuroscience” of brain tumors by understanding how glioma alters and communicates with the neuronal microenvironment. Finally, in a completely separate set of studies, we are interested in the functional genomics of brain tumors. In the age of genomics, we have so much information about mutation landscapes for most tumors, yet we don’t know what any of it means. We are building native, in vivo systems in the brain to initiate functional screening of mutations found in glioma.

What has been a successful guiding principle for mentoring in your lab?

This is pretty simple. As a mentor, it’s critical to remember that your success is directly tied to their success. If you want to have a successful lab, then you have to invest in your mentee’s success and recognize that you need them as much (if not more!) than they need you. Towards this, I have learned that every student and post-doc learns and operates differently, that there is no single curriculum for all. It’s important to adapt your mentoring style to the mentee, to ensure that they are in the best position to be successful.

Tell us why you research? What motivates you to keep forging ahead?

Doing science is something that has become a part of who I am and that I must do. I’m motivated by the new and exciting directions that my lab is now taking, these are questions and areas I never imagined exploring. I’m also motivated by the pursuit of knowledge, by asking a question and working diligently to find an answer. Most of the time we find unexpected answers and this is what leads to new pursuits. This is probably responsible for the current state of my lab!

From your early experiences as a faculty, what advice would you give to scientists interested in pursuing a similar path?

This career path (becoming an independent investigator in the biomedical sciences) is not for the faint of heart, it takes a very long time to get to this stage. So, the first piece of advice is to exercise patience and find mentors that you trust. Furthermore, not only do you have to be smart and dedicated, but you also have to be lucky. The way you create luck is by working as hard as possible, executing as many experiments as possible—eventually something will reveal itself! This leads me to a related piece of advice: having an open mind. Its ok to be wrong (I am often wrong) and its ok if your pet hypothesis is incorrect (mine are often wrong). It only takes one great idea or result to kick start or spark a project and you need to be intellectually receptive to ideas and data that you did not expect or anticipate. Finally, the last piece of advice is to be mindful of your scientific niche. Too often, I have seen brilliant young scientists tackle daunting questions that are being pursued by an army of laboratories. This is not a winning strategy. Hence, my advice is to be strategic about the fields you enter and the questions you ask, because your very survival as an independent investigator depends on it.

And finally, what advice would you give to your young self about your path in science?

Have complete trust in yourself.

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