Cristina Rodríguez: Developing Optical Microscopy Tools for Deep Tissue in vivo Imaging of the Nervous System

The School of Engineering & Applied Science is proud to welcome its newest faculty members for the 2022-23 academic year. The large influx of faculty members – 13 so far, with more to be announced soon – marks the rapid growth of the School and investment in the research areas illustrated in the SEAS Strategic Vision.

The latest faculty arrivals are valuable additions to the chemical and environmental, computer science, and electrical engineering departments. Their expertise includes sustainability, artificial intelligence, robotics, quantum computing, cybersecurity, and optoelectronic materials.

Upon their arrival, we asked these new faculty members questions about their work, their motivations, potential collaborations, and much more:

Cristina Rodríguez, Biomedical Engineering


Caracas, Venezuela.

Prior academic history:

I began my journey in physics as an undergraduate student in Caracas, Venezuela. This journey continued during my PhD at The University of New Mexico, under the supervision of Professor Wolfgang Rudolph, where my research focused on nonlinear optics for efficient frequency conversion and microscopic imaging. Driven by my passion for understanding the brain, I joined as a postdoctoral scholar the group of Professor Na Ji, at the HHMI Janelia Research Campus and later at the University of California, Berkeley. Here, I worked building the next generation of optical microscopes to understand how the brain works, pushing the boundaries on imaging depth, resolution, and speed.

How would you summarize your research?

The focus of my research program is to develop optical tools for imaging deep into biological tissues with high spatial resolution, and in doing so, advance our understanding of previously underexplored biology. To do this, we use a multidisciplinary approach involving physics, nonlinear optics, and microscopy development.

In particular, my lab works with an imaging method called three-photon fluorescence microscopy – currently the imaging method of choice for non-invasive deep tissue cellular and subcellular resolution imaging of the central nervous system in animal models. We also work with adaptive optics – a method originally developed for astronomical telescopes – to actively shape the wavefront of the light used by our microscopes, and compensate for the aberrations introduced by tissues, making it possible to achieve synaptic-level resolution at depth.

Using these tools, my lab seeks to advance our understanding of how we sense touch – by imaging neuronal activity in the mouse spinal cord and brain – under both healthy and pathological conditions. My lab will also develop novel imaging probes, for applications including deep tissue vasculature imaging, cell tracking, light-activated therapeutic delivery systems, and optogenetic manipulation of neural circuits.

What inspired you to choose this field of study?

Ever since I was an undergraduate student in physics, I have been interested in developing and applying tools that allow us to observe what’s invisible to the naked eye, enabling us to ask questions that we could not ask otherwise. This passion has taken me on a fascinating journey that has included studying black holes and brains!

What inspired me to choose my current field of study, is a desire to understand how the nervous system works. Understanding this is key because when neural circuits malfunction, due to injury or disease, the effects can be devastating. In the brain, the consequences can manifest, for example, as cognitive deficits (including language impairment, memory loss). In the spinal cord, the effects can range from abnormal pain sensations to a permanent loss of feeling and motor function. To find effective treatments, we need to understand how these circuits work. To achieve this, we need non-invasive methods to visualize them in a natural and physiological state, that is, in live animals. The state-of-the-art optical microscopes that I develop allow me to visualize both the morphology and the activity of large populations of neurons, deep inside of the brain and spinal cord of live animals, with the ability to resolve single neurons and even synapses.

Where do you see the field 10 years from now?

There have been enormous advances in the field of deep tissue optical imaging in the last decade, and I am excited to see all the new biology that will be discovered as a result. In the next 10 years, I hope to see advances in different areas, including: (1) Faster wavefront shaping devices and methods, enabling higher speed wavefront measurement and correction. (2) More robust laser sources for higher order multiphoton excitation. (3) Brighter imaging probes. (4) An increase in mechanisms for technology dissemination and training, enabling the adoption of advanced optical imaging tools by more biology labs.

What brought you to Yale?

The interdisciplinary and highly collaborative environment of the Department of Biomedical Engineering, as well as the strong and rapidly growing biomedical imaging community, make Yale an ideal place for my research program to take off. I am looking forward to the many exciting opportunities for collaborations aimed at deciphering biological phenomena in health and disease using the optical technologies my lab will establish.

What areas outside of Biomedical Engineering do you seek to create impactful research collaborations or partnerships?

Because my research lies at the interface between cutting-edge optical microscopy and neuroscience, the strong neuroscience community at Yale – including the recently established Wu Tsai Institute – will provide many exciting opportunities for collaborations.

Are there any courses that you look forward to teaching/creating?

Yes! I look forward to teaching Biophotonics & Optical Microscopy. I am also eager to design a class or seminar on novel optical microscopy techniques for in vivo biological imaging, and thus expose students to my own research.

What are your interests outside of the lab?

Spending time outdoors hiking, climbing, running, camping, skiing... is one of the things I enjoy the most – a passion that I share with my partner and two sons. I also play several percussion instruments, and whenever possible, I like to get my hands on crafty things such as pottery, jewelry making, and origami.

What is the best New Haven Pizza?

I like Frank Pepe and Modern Apizza!

Back to the 2022-2023 New SEAS Faculty Profiles