First person – Michael Flores

Michael Flores

Describe your scientific journey and your current research focus

I started my scientific journey as an undergrad at New York University (NYU) where I studied Biology with an interest in genetics. Towards the end of my undergraduate studies, I started working as a research assistant in the lab of Dr Silvia De Rubeis at Mount Sinai's Icahn School of Medicine. There I was introduced to neuroscience, a field I was previously unaware of. I became fascinated by the field of neuroscience and decided to continue doing research in Dr De Rubeis's lab as a full-time research assistant post-graduation. After two years of learning how to drive a project from start to finish and what it means to be a scientist, I decided to pursue my PhD. Now, as a PhD student at the University of California, San Francisco, I am currently focusing on how inter-individual variations in neural activity during learning lead to individual differences in learning trajectories.

Who or what inspired you to become a scientist?

Science was my favorite subject in middle school and high school, but I never considered becoming a scientist until college. Initially, I aspired to become a medical doctor, but my first experience visualizing the diversity of cell types in a mouse brain under the microscope in Dr Silvia De Rubeis's lab reshaped my career goals. Learning that these distinct neuronal populations work together to drive complex behaviors sparked my life-long curiosity for the nervous system. My research experience in Dr De Rubeis's lab inspired my desire to pursue a career in science.

How would you explain the main finding of your paper?

DDX3X syndrome is a rare neurodevelopmental disorder that affects both motor and cognitive functions and, in many cases, is accompanied with structural brain malformations. Using a mouse model of DDX3X syndrome, we investigated how the development and circuit organization of a layer five neuronal subpopulation in the cortex is disrupted. This subpopulation, identified by the co-expression of the transcription factors CTIP2 and BRN1 (CTIP2+BRN1+), emerges early during embryonic development and persists into adulthood. Our experiments revealed region-specific alterations in the distribution of CTIP2+BRN1+ neurons in mice with DDX3X mutations. This disruption was observed specifically within the medial cortex during embryogenesis and in the motor cortex in adulthood. Further, we found that mutations in DDX3X lead to excessive of CTIP2+BRN1+ cortico-brainstem projection neurons, which highlights an important circuit insight on how brain function could be affected by DDX3X mutations.

What are the potential implications of this finding for your field of research?

Mouse models of DDX3X syndrome exhibit delays in reaching motor milestones and adult motor deficits, recapitulating some of the motor symptoms observed in patients with DDX3X syndrome. We revealed the effects of DDX3X mutations on the laminar distribution of a specific cortical subpopulation and its cortico-brainstem projections. This provides valuable insights into the neural basis underlying the affected motor behavior by DDX3X mutations. The identification of this affected population and its circuit opens avenues for further investigation that might include manipulation of circuit function for ameliorating the motor deficits caused by DDX3X syndrome.

Which part of this research project was the most rewarding?

Working alongside co-author Dr Marta Garcia-Forn and the rest of the team has been the most rewarding. Every single one of my colleagues and mentors have taught me so much. From learning to perform surgery on rodents for labeling projection neurons to learning how to rigorously design experiments to answer outstanding biological questions. This entire experience has shaped how I think about science and has inspired me to continue doing neuroscience research.

What do you enjoy most about being an early-career researcher?

I really enjoy learning something new every day. Whether it's a new technique or an interesting finding I read from a paper related to my area of research – everything is still new to me, and I am constantly learning. I also value the responsibility and independence that comes with being an early-career researcher – from making decisions about the project to designing my own experiments. Also having the opportunity to meet other early-career researchers through conferences and courses has been just as enjoyable and has allowed me to develop a network of early-career researchers who support one another.

What piece of advice would you give to the next generation of researchers?

My advice is to not let self-doubt hold you back from seizing opportunities. If there is a chance for you to present your work for the first-time, take it! While it may feel daunting at first, you will learn so much about communicating your science to an audience beyond your lab. If there is a lab whose research deeply interests you, do not hesitate to cold email them expressing your enthusiasm. The same applies to applying for grants or PhD programs, you might surprise yourself and regardless will learn so much during the process. The entire scientific environment can be intimidating, but I think it is important believe in your own potential, take risks, and trust in your passion and hard work.

What's next for you?

I am excited to continue studying neuroscience as a PhD student, where I am using electrophysiological techniques to record the activity of neuronal populations while young songbirds are learning to sing. By doing so, I hope to reveal how inter-individual variations in learning emerge from the nervous system. I also look forward to working with my institution to increase inclusivity, diversity, and equity in science, so that students from all backgrounds are empowered to pursue careers in science.