Visitor of the Week: Christian Harris

Meet Christian Harris! The Ph.D. Candidate is a member in the lab headed by Dr. Mary-Louise Risher, Ph.D., and is co-affiliated with Joan C. Edwards School of Medicine at Marshall University and the Hershel Woody Williams Veteran Affairs Medical Center. She took part in last week’s virtual Glia in Health & Disease meeting – her first meeting at CSHL.

Tell us about your research.
My project is investigating the intersection of adolescent binge ethanol exposure and traumatic brain injury (TBI). I am particularly interested in understanding how binge drinking impacts the severity of traumatic brain injury and changes the propensity to consume alcohol later in life.

How did you decide to focus on this area/project?
In part because of the multiple TBIs that I sustained during my soccer career, brain injury has always been of interest to me  and I was looking to study the cellular mechanisms of TBI. Similarly, my PI Dr. Mary-Louise Risher was looking to add a TBI component to her model of adolescent binge drinking and this turned out to be a great opportunity for me to join her lab. Following several conversations, we agreed an alcohol-TBI project would be an innovative new direction that would provide valuable insight into how astrocytes respond to a variety of insults.

What and/or who is the inspiration behind your scientific journey?
My family is a huge inspiration to me: My mother (a physician) and my father (a mathematics educator) introduced me to STEM fields at a young age. Throughout my life my family has always encouraged me to think outside the box, to be innovative, and to remain diligent and steadfast in all that I do. My family is always there for me with words of encouragement. I am beyond thankful for such an amazing support system.

What impact do you hope to make through your work?
TBI is a major cause of death and disability in the United States. I hope to find a therapeutic target to aid in TBI recovery and limit acute and long-term brain damage. I believe that this work could change the trajectory of TBI treatments.

Where do you see yourself in five years?
In five years I hope to be conducting both clinical (studying the effects of TBI in athletes or veterans) and translational research. I want to investigate the intersection of TBI, individual response to treatment, and age of insult. I’m also interested in repetitive TBI exposure. I would also like to continue animal studies where I can further explore the role astrocytes on neuronal recovery following TBI. Understanding the changes in astrocyte function may be the key in limiting acute and long-term brain damage and developing targeted treatments.

What do you love most about being a researcher?
Research stimulates my imagination and creativity. Being a researcher gives me limitless opportunities and the freedom to formulate, develop and test new ideas.  I particularly enjoy the investigative process as it allows me to turn my ideas into reality. Being a researcher is exciting and humbling yet so valuable and rewarding.

What drew you to attend this meeting?
I am relatively new to the field of glia, so this meeting is a great opportunity to expand my knowledge of the field as well as learn from some of the best researchers in the world. Also, my PI Dr. Risher and labmate Christopher Walker had a really interesting poster during the meeting on the impact of adolescent binge ethanol exposure on astrocyte structure and function.

What is your key takeaway from the Meeting; and how do you plan to apply it to your work?
The key takeaway from this meeting is that glial cells may hold the key to unlocking many of the mysteries surrounding the mechanisms of disease and injury. There were multiple talks and posters on astrocyte reactivity, traumatic brain injury, and alcohol that are directly related to my research. I am hoping to apply a few of the presented genetic, imaging, and data acquisition techniques to my work.

What feedback or advice would you share with someone considering to participate in this meeting?
Meetings can be overwhelming, I recommend going through the meeting program a few days before the meeting starts. Find talks and posters that are of interest to you, read the abstracts, and develop a schedule. Make sure to factor in some free time for networking, come with an open mind, and most of all have fun and enjoy the meeting!

What’s the most memorable thing that happened during the Meeting?
There are so many! Overall, I thoroughly enjoyed interacting with so many fellow researchers from various labs, research backgrounds, and countries. Being able to exchange various thoughts and ideas while making lasting connections is invaluable. I have learned

Thank you to Christian for being this week's featured visitor. To meet other featured researchers - and discover the wide range of science that takes part in a CSHL meeting or course - go here.

Image provided by Christian Harris

Repeat Visitor: Tatiana Schnieder

Among the ~9,000 scientists we hosted this year, a number of them participated in multiple meetings and/or courses. Kicking off the 2018 edition of our Repeat Visitor series is Tatiana Schnieder, an assistant professor of clinical neurobiology at Columbia University and an adjunct assistant professor at Hunter College. Tatiana divides her work between two research labs – the neuropathology laboratory of Dr. Andrew Dwork at Columbia University Irvin Medical Center and epigenetics laboratory of Dr. Fatemeh G. Haghighi at Mount Sinai School of Medicine. This year, Tatiana took part in the 83rd CSHL Symposium on Quantitative Biology and joined the ranks of both the CSHL Protein course (Expression, Purification, & Analysis of Proteins & Protein Complexes) and The Genome Access Course (TGAC). Previously, she presented a poster during the Glia in Health & Disease meeting in 2016 as well as attended Blood Brain Barrier that same year. We reached out to Tatiana to chat with her about her experiences in CSHL meetings and courses, and to learn more about what keeps her coming back to campus.

Tell us about your research interests.

My research is focused on the question of brain-periphery interactions in psychiatric disorders. To be more specific, I am currently investigating whether or not the reported relationship between suicide and central and peripheral inflammation is mediated by changes in blood-brain barrier (BBB) permeability.

How did you decide to make this the focus of your research?

During my doctoral training, I investigated prefrontal white matter microglia in individuals who died by suicide; and although I did not find any significant differences in microglial activation between suicides and non-suicides, suicide decedents had significantly higher densities of juxtavascular phagocytic cells in dorsal white matter than diagnostically-matched non-suicide decedents. Interestingly, however, studies of animal models of psychiatric symptoms have attributed maladaptive behavior in rodents to peripheral inflammation and to the influx of peripheral immune cells into the brain parenchyma. These findings and my own findings in postmortem human brains prompted me to investigate the involvement of peripheral immune cells in pathology associated with completed suicide. Further research revealed that non-parenchymal immune cells do not contribute to the increase in perivascular cell density that we observed in suicide; which suggests that resident microglial cells -- rather than non-parenchymal immune cells -- cross-communicate immune responses between the periphery and central nervous system in suicide. Moreover, those who died by suicide had a lower surface area density of microvessels in dorsal white matter -- the same brain region where I found increased densities of perivascular phagocytes. Cumulatively, these findings indicated that changes in the properties of the neurovascular unit could be contributing to pathological changes that lead to suicide. This piqued my interest in the role of BBB in psychiatric disorders. The goal of my current project is to determine if completed suicide is associated with transcriptional, epigenetic, or protein changes in the neurovascular unit.

Expression, Purification & Analysis of Protein & Protein Complexes Class of 2018

What led you to apply for the Protein course and how has it contributed to your work?

I applied to the Protein course to find answers to the challenges I faced during the preparation of my samples for HPLC/mass spectrometry. To assess changes in the expression level of key proteins crucial for BBB function and identify novel differentially expressed proteins, I use HPLC/mass spectrometry proteomics to interrogate protein expression profiles in isolated microvessels. To investigate BBB changes in psychiatric disorders and suicide specifically, I wanted to optimize a microvessel isolation protocol from postmortem frozen human tissue. It was important for me to develop the best method for the extraction of cytosolic, membrane, and transmembrane proteins that seal a gap between the brain endothelial cells. The two-week course gave me a lot of hands-on practice in protein isolation and, through extensive communication with the Instructors and use of the course materials, I was able to come up with the optimal protocol for my project. My main takeaway from the course is that it is imperative to learn as much as possible about your protein/s of interest before you start your experiments. Know your target well because what may work for one protein can be detrimental to another.

How about TGAC? Why did you register for it and what is your key takeaway?

My BBB project involves data that will require knowledge of bioinformatics, and I want to understand what goes into the analyses of the data I produce at the bench. I took TGAC to start learning how to analyze high-throughput data obtained using next-generation sequencing methods and mass spectrometry. As for my key takeaway: Apply what you learn in the course without delay. To acquire a new skill, one needs to practice often – if not daily – therefore it is important to “play” with your data so as to avoid forgetting what you pick up from the course.

The two courses have very different formats: the Protein course consists of hands-on training in a laboratory setting while The Genome Access Course is purely computational. What can you share about the differences or similarities between your experiences in the two courses?

The Genome Access Course Class of 2018 (Spring)

The two courses I took were indeed very different: TGAC was a short two-day course, whereas Protein course was two weeks long and so requires a completely different level of commitment. What is expected of you is also different: TGAC course is mostly lecture-based with some hands-on computer work, and the Protein course is mostly lab-based with lectures sprinkled throughout the day and evening. You cannot really choose to opt out, and by the end of the first week you already feel like you are a part of a team. In fact, working in a team and as a team will be the main mode of learning in a longer course. Irrespective of which course you decide to take, you will be taught by the top experts in the field within a friendly and supportive learning environment, where you will always have the ability to discuss and clarify concepts that may be confusing. It was an amazing experience: I was challenged to step out of my comfort zone, which is how personal and professional growth happens.

The focus of the CSHL Symposium changes annually. This year its topic was “Brains & Behavior: Order & Disorder in the Nervous System,” with an emphasis on neuroscience and related technologies. Besides the overall topic, what attracted you to participate in it?

Once you graduate, it is easy to focus on your specific area of research and, sometimes, you lose sight of the bigger picture. I strive to prevent this from happening to me. As a college professor, I need to stay abreast of the new discoveries in the field of brain research, and attending the Symposium was a perfect way to catch up with the latest findings. It provided a diverse range of topics and speakers from top-notch brain research labs. When this Symposium hones in on this topic again, I would recommend aspiring neuroscientists to attend. If you haven’t yet decided what you want to dedicate your research to or are looking to expand your network, this is a great conference.

Since you’ve now experienced both meeting and course life at CSHL, what differences or similarities did you notice about the two program types?

The courses had a much more focused agenda and required a few prerequisites so you are more likely to meet people who share similar professional or academic experiences as you. The meetings, on the other hand, were eclectic and brought together people from very diverse backgrounds. But in both instances, expect to be surrounded by like-minded people enthusiastic about science and the discoveries it brings.

What did you like most about your meeting and courses this year?

I am very lucky to live a short train ride away from CSHL. Since the first CSHL meeting I attended in 2016 on Glia in Health and Disease, I keep coming back because the quality of the meetings and courses have always been stellar, and the content and organization of the events always meet my expectations. In fact, I am looking forward to attending the Blood Brain Barrier meeting in 2019.

Both the Protein course and TGAC will return to the Laboratory in 2019; and applications are already being accepted. Apply to the Protein course by January 31, 2019 here.

Thank you to Tatiana for sharing with us her experience, and we look forward to having her back at the Laboratory again. To meet other featured scientists - and discover the wide range of science that takes part in a CSHL meeting or course - go here and here.

Visitor of the Week: Predrag Janjic

Meet Predrag Janjic of the Macedonian Academy of Sciences and Arts (Republic of Macedonia). Predrag is associated with the Laboratory of Complex Systems and Networks led by Ljupco Kocarev, and with the Research Program in Psychiatric Diseases led by Andrew J. Dwork of the New York State Psychiatric Institute at Columbia University. The research scientist is on a multi-week trip in New York – first to take part and present a poster in the 2018 Glia in Health & Disease meeting titled “Multistability in a model of membrane voltage dynamics in hippocampal astrocytes—Interplay between Kir and K2p currents” and then to meet with his States-side collaborators.

What are your research interests? What are you working on?
The main focus of my present work is computational modeling of glial cells, both their structure and function. Within the structural studies we try to quantitate myelin in psychiatric disease, while on the functional side, I develop dynamical models of conductivity of astrocytic membrane.

How did you decide to make this the focus of your research?
While I knew cell-level modelling would be the focus of my work, as I was considering the particular phenomena I should concentrate on, it was a striking realization that computational cellular neuroscience had almost completely ignored glial cells during the last few decades, or have modeled their roles in a rudimentary way. From a biophysical perspective, I found it unacceptable and decided to take a closer look into how biophysical theory could describe some of the basic experimental properties. For getting into closer contact with the real issues and challenges, apart of the collaboration with Columbia University on myelin, for functional cell-level modelling I collaborate with Prof. Christian Steinhaüser’s lab in Bonn and Prof. Pavle Andjus’ lab in Belgrade where advanced neurobiology of glia is being explored experimentally.

How did your scientific journey begin? 
After graduating with a degree in electrical engineering and computer science, I pursued a masters in the theoretical physics of nonlinear phenomena from Ss. Cyril and Methodius University in Skopje; where my interest in dynamical descriptions of neuronal membranes began. The freedom I was given by Prof. Kocarev to explore less established areas enabled me to carry over my earlier interest into Ph.D. studies, focusing on the variations of modeling frameworks in non-excitable (or non-spiking) cells. The NIMH/Fogarty-funded research led by Columba University provided me with the critical opportunity to join a larger research program and pursue neuroscience.

Was there something specific about the Glia in Health & Disease meeting that drew you to attend?
I was attracted by: 1) the growing evidence from several labs that specific glial potassium-channel families (which I study) are implicated in more and more disordered conditions, and 2) the possibility to have face-to-face discussions on those implications and experimental observations.

What is your key takeaway from the meeting?
During the last several years, I have struggled to find my home community. The computational neuroscience community – where I belong on paper – still unfortunately stands aside on most of the glial phenomena. On the other hand, the concepts and methods used by the computational neuroscience community are still a bit abstract for the glial biologists, where molecular studies presently dominate. Computational studies of glia will have to bridge the gap between the experimental observations and their quantitative descriptions, and CSHL is a very unique place where both experimentalists and theoreticians feel at home. The explosion of molecular findings will show  researchers like me where to look when refining the computational descriptions of the phenomena we observe.

What did you pick up or learn from the meeting that you plan to apply to your work?  
This was the first meeting I attended where a notable number of leading researchers in glial biology were present. I needed to get a first-hand account of the molecular studies aimed at showing what (de)regulates the ion channel populations I am quantitatively modeling, as well as what is the latest in the imaging and molecular studies of myelin. 

If someone curious in attending a future iteration of this meeting asked you for feedback or advice on it, what would you tell him/her?
As the glial biology community is definitively growing, the Glia meeting at CSHL will further gain popularity. And since both, the cell-level and molecular biological contexts are addressed here, CSHL is really a great place to get inspired  while meeting and working with other glial biologists.

What do you like most about your time at CSHL?
The CSHL campus has a unique quality conducive to relaxing and thinking about what really inspires you. The history-rich facilities, artistic touches in each and every corner, supportive staff, and the great food will make anyone feel really pleasant.

Thank you to Predrag for being this week's featured visitor. To meet other featured scientists - and discover the wide range of science that takes part in a CSHL meeting or course - go here.