Announcing: RNI’s first student travel awards

Regeneration Next is pleased to announce travel grants to support six students. The travel award supports graduate students who present tissue regeneration-related research at relevant scientific meetings. Our first round of awardees are:

Colleen Drapek, Benfey Lab, Department of Biology. Colleen will attend the American Society of Plant Biology meeting and will present her work on “The Minimal Gene Regulatory network for Arabidopsis Root Endodermis differentiation.”

Lauren Heckelman, DeFrate lab, Department of Biomedical Engineering. Lauren attended the Orthopaedic Research Society conference and presented two projects: “In Vivo Behavior of Patellar Cartilage in Response to and Twenty-Four Hours following Running” and “In Vivo Exercise-Induced Glenohumeral Cartilage Strains.”

Jennifer Kwon, Gersbach lab, Department of Biomedical Engineering. Jennifer will attend the International Society for Stem Cell Research meeting to present her work on “Directing skeletal myogenic progenitor cell lineage specification with CRISPR/Cas-9 based transcriptional activators.”

Jason Wang, Bursac lab, Department of Biomedical Engineering. Jason will attend the EMBO conference on Muscle Wasting and will present his work on “Developing an in-vitro model for human skeletal muscle regeneration.”

Lifeng Yuan, Wang Lab, Department of Pharmacology and Cancer Biology. Lifeng will attend the International Society for Stem Cell Research meeting and will present work on “Negative regulation of mitochondrial intermembrane peptidase drives metabolic alteration and cell death blockage for initiating cellular senescence.”

Congratulations to these deserving students! The next deadline for the Regeneration Next travel grants will be September 28, 2017. Details and application instructions are here.

New RNI Postdoctoral Fellows announced!

Regeneration Next is pleased to announce the 2018 – 2020 Regeneration Next Postdoctoral Fellows. This group of outstanding scientists was chosen from a competitive pool of applicants. Now in our second year, the RNI Postdoctoral Fellows program identifies promising young researchers who will have a key role in shaping and growing the tissue regeneration community at Duke. Please join us in congratulating our four new RNI Fellows!

Valentina Cigliola, Ph.D.

Valentina Cigliola received her PhD in Biology at the University of Geneva, in Switzerland, where she worked on mechanisms of islet cell fate changes during pancreas regeneration in diabetes, under the supervision of Dr. Pedro Herrera. She also was involved in characterizing a variant form of the human connexin 36 protein altering β-cell function and survival, under the supervision of Dr. Paolo Meda. She recently started a postdoctoral fellow position in the laboratory of Dr. Kenneth Poss, in Duke’s Cell Biology department. As an RNI fellow, she aims to characterize the cellular and molecular basis of heart regeneration, whose discovery is highly relevant to human disease such as ischemic myocardial infarction and heart failure.

Brian Cosgrove, Ph.D.

Brian recently started as a postdoctoral fellow in Duke’s Department of Biomedical Engineering, where he works in Dr. Charles Gersbach’s lab. During his PhD training at the University of Pennsylvania, Brian developed new biomaterial platforms that better recapitulate the developmental mesenchymal microenvironment in order to more precisely interrogate how multiple mechanobiological signals are integrated by stem cells. As an RNI fellow in Dr. Gersbach’s lab, he hopes to further understand how mechanical cues can influence the epigenetic state of stem cells and utilize this information to better direct and maintain stem cell fate decisions in therapeutic applications.


Abdelhalim Loukil, Ph.D.

Halim recently started a postdoctoral fellowship in Dr. Sarah Goetz‘s laboratory in the Department of Pharmacology and Cancer Biology at Duke’s School of Medicine. He has focused his efforts on studying the biogenesis of a fascinating tiny organelle called “primary cilium.” He recently published exciting results on the critical role of the daughter centriole in cilia formation. The primary cilium acts as a specialized organelle that regulates several developmental signaling pathways. Disrupting cilia structure or function causes numerous hereditary human diseases commonly called ciliopathies. These disorders are generally accompanied with a range of neurological impairments and neurodegeneration. With the support of the Regeneration Next Fellowship, he will investigate the in vivo roles of primary cilia in neural function. He aims to dissect the molecular mechanisms by which cilia mediate neuronal function and homeostasis in adult brain.

WenXiu Ning, Ph.D.

Wenxiu completed her doctoral work at the Chinese Academy of Sciences. Her previous work uncovered a novel crosstalk between microtubule and F-actin which contributes to wound healing of epithelial cells. To extend her studies from cultured cells to understand how tissues are made, she has joined Dr. Terry Lechler‘s lab in Duke’s Department of Dermatology as a postdoctoral fellow. With the support of RNI fellowship and resources in the Lechler Lab, she plans to determine the functions of intermediate cells and their proliferation in epidermal development and to uncover cell intrinsic and extrinsic pathways that promote intermediate cell proliferation in order to better understand how the skin stratifies and how epidermal cells influence and communicate with each other to achieve homeostasis and wound healing.

The next call for applications for Regeneration Next Postdoctoral Fellowships will be released in September 2017. Read about last year’s inaugural cohort of Postdoctoral Fellows here.

Durham Students Give Themselves a Hand Up

(This post originally appeared on the Duke Research Blog on April 7, 2017 and is reposted here in its entirety).

Picture this: a group of young middle schoolers are gathered trying to get a “hand” they’ve built out of drinking straws, thread and clay to grasp a small container. What could such a scene possibly have to do with encouraging kids to stay in school and pursue science? It turns out, quite a lot!

Angelo Moreno (right), a graduate student in molecular genetics and microbiology, helps students with their soda straw hand.

This scene was part of an event designed just for boys from Durham schools that took place one March evening at the Durham Marriott and Convention Center. It was hosted by Made in Durham, a local non-profit focused on helping Durham’s young people graduate from high school, go to college, and ultimately be prepared for their careers, and My Brother’s Keeper Durham, the local branch of former President Obama’s mentoring initiative for young men of color.

The first evening of a convention centered on building equity in education and was geared toward career exploration. Each of the boys got to choose from a series of workshops that highlighted careers in science, technology, engineering, art, and mathematics — also known as STEAM. The workshops ranged from architectural design to building body parts, which was where they learned to build the artificial hands.

Sharlini Sankaran, the executive director of Duke’s Regeneration Next Initiative, who heard about my outreach activities from earlier this year, contacted me, and together we drummed up a group of scientists for the event.

With the help of Victor Ruthig in Cell Biology, Angelo Moreno in Molecular Genetics and Microbiology, Ashley Williams in Biomedical Engineering, and Devon Lewis, an undergraduate in the Biology program, we dove into the world of prosthetics and tissue engineering with the young men who came to our workshop.

Angelo Moreno (right), a graduate student in molecular genetics and microbiology, helps students with their soda straw hand.

Biology student Devon Lewis (top) works with several of the students.

After some discussion on what it takes to build an artificial body part, we let the boys try their hand at building their own. We asked them what the different parts of the hand were that allowed us to bend them and move them in certain ways, and from there, they developed ideas for how to turn our household materials into fully functioning hands. We used string as tendons and straws as finger bones, cutting notches where we wanted to create joints.

There was a lot of laughter in the room, but also a lot of collaboration between the different groups of kids. When one team figured out how to make a multi-jointed finger, they would share that knowledge with other groups. Similar knowledge sharing happened when one group figured out how to use the clay to assemble all their fingers into a hand. Seeing these young men work together, problem solve, and be creative was amazing to watch and be a part of!

According to feedback from event organizers, “ours was the most popular session!” Sharlini said. When we reached the end of our session, the kids didn’t want to leave, and instead wanted to keep tinkering with their hands to see what they could accomplish.

The boys had a lot of fun, asked a lot of good questions, and got to pick our brains for advice on staying in school and using it to propel them towards career success. I have distilled some of the best pieces of advice from that night, since they’re good for everyone to hear:

  • Don’t be afraid to ask a lot of questions.
  • Don’t be discouraged when someone tells you no. Go for it anyways.
  • Don’t be afraid of failure.
  • And don’t think you have to fit a particular mold to succeed at something.

“I left feeling really inspired about our future generation of scientists and engineers,” Sharlini said. ”It’s good to know there are so many Duke students with the genuine and selfless desire to help others.”

It was a joy to participate in this event. We all had fun, and left having learned a lot — even the parents who came with their sons!

Outreach like this is incredibly important. Being mentors for young people with a budding interest in science can make the difference between them pursuing it further or dropping it altogether. Engaging with them to show them the passion we have for our work and that we were kids just like they are allows them to see that they can do it too.

Guest Post by Ariana Eily

5 questions with Humacyte’s Jeff Lawson

Sharlini Sankaran spoke with Dr. Jeff Lawson, who is on sabbatical from Duke University to serve as Chief Medical Officer (CMO) for Humacyte, about his work with engineered blood vessels. Humacyte’s investigative human acellular vessel recently received one of the US Food and Drug Administration (FDA)’s first Regenerative Medicine Advanced Therapy (RMAT) designations.

What excites you about your work?
What excites me is the potential to regenerate something as simple as a blood vessel; that may be a platform which we can use to regenerate a litany of organs in the future. I’m reminded that the first barrier to transplantation wasn’t the immunosuppression, but the vascularization. When Alexis Carrel won the Nobel prize it wasn’t for transplantation, but for vascular anastomosis – which lay the groundwork for him to one day do the first kidney transplant. So, I think we have to get the blood vessel right first before you can do any more complex organ, because they are all absolutely dependent on the blood vessels. In fact, the blood vessel isn’t just a tube – the vasculature functions as its own organ with its own physiology. So, to create a functioning blood vessel from a manufacturing standpoint is a very exciting opportunity and reflects a very do-able state of science in 2017. Some day, we may 3D print an organ which we can then pre-incubate with stem cells, which may then differentiate into a kidney. And I think we should try! In the 90s, when we first started doing this, we didn’t know that it would take twenty-some years to get it right and to be in Phase III clinical trials.

So that’s where Humacyte is now, right? Tell me more about your role at Humacyte and what drives you.
Yes, we are in global clinical trials right now. We just enrolled our 190th patient in our global clinical Phase II trial. It’s so exciting. The other exciting thing is, that I get to participate in something which may impact the lives of patients whom I’ve cared for. You can’t save humanity as one surgeon – you can only do one surgery at a time and there are more to be cared for. And you get to a phase in your career where you think, maybe I can impact 10,000 patients, maybe I can work on something that changes the way care is done for the better. So for me, the opportunity to change the vascular platform which surgeons can use to treat patients is very unique and very impactful. You only get one shot at this kind of chance – that is part of what drove my decision to uncouple my day job as an academic vascular surgeon for a period of time to get the clinical execution of the trial done by taking the position at Humacyte.

Describe why your research, and Humacyte’s products, are so important to human health.
What we’re doing is making the blood vessels that can be used in the initial trial. We have a number of products in clinical trials and the one that’s furthest along the regulatory path is in dialysis care. There’s a huge unmet need for patients to have blood vessels working in their arm that they can then use to get dialysis. We have also already initiated a number of Phase II clinical studies that are more arterial reconstruction based. These fall into two domains: one for patients with peripheral arterial disease, and the possibly more intriguing one is for emergency vascular trauma, when someone is injured and you have no synthetic material to reconstruct their blood vessels with today – we think we can provide a human tissue that is safe and potentially infection resistant.

We have support from the Department of Defense to develop a blood vessel that could be deployed to far forward military facilities, civilian trauma centers, and can also be used to reconstruct failing arteries from conventional atherosclerosis in an aging population. Where we started this story a long time ago, was to be a conduit for coronary heart surgery and we have every intent of having the vessels available in a smaller size. We currently make it in one size for clinical application but we have the capacity to manufacture the blood vessel in different sizes and shapes.

We’re also looking at extending the manufacturing of tubes to other organs outside the vascular system. We are looking at things like urinary conduit, and the esophagus, and the trachea. We would first like to be able to make different types of tubes that are necessary and can be replacement human tissue, and at that point we can look at transitioning to more complicated regenerative medicine. We’ve actually done some preclinical work already with urinary conduit, we know we can make the constructs for things like trachea and esophagus. It takes the same conceptual platform of taking human cells, and making the relevant shape and structure. The other questions are, do you have to have unique attributes to the matrix that’s made? If it’s placed in a different anatomic location, will it remodel and repopulate with the host cells in similar fashion? Those are questions that will be answered in the next 20 years – certainly through the rest of my career!

What has been your biggest challenge in transitioning from the university environment to chief medical officer in a startup, recognizing you’re still doing both?
I love being a physician-scientist, it’s what I’m emotionally suited to do. I never intended to become an expert in certain regulatory, or business-oriented, or administrative things. It’s interesting where your career takes you – I’m doing things that I never trained to do. The hardest thing for me, has been giving up the things I know how to do well, like operating. The operating room is such a comfortable environment for me, and I’ve been doing it for 20 years – being out of that environment has really given an appreciation for doing the things that are part of a conventional clinical practice.

One thing I’ve learned: as a CMO, you have to be committed to working as a team. As a surgeon, you are of course working with your surgical team, but a lot of the final decision-making is the surgeon’s call. In the corporate world, there are a lot of different people that you have to negotiate with as you make decisions that impact the company. So that has been a different skillset than saying “I’m the surgeon, I’m making this decision.” It’s a skillset that says: “all right we’ve got to sit down and negotiate and talk about how we are going to solve this problem.” So that’s been a transition that’s been a good one, but a challenge. Many of these decisions are made at an organizational level where the CEO, CMO, COO and a few other people all have to concur if we are going to proceed with a decision.

One of the things that’s really challenging from a company standpoint, is that we have all of this exciting stuff that’s happening and we are growing so fast. You raise enough money to do these three clinical trials, you got to jump all in: you got to finish the studies, you gotta be able to manufacture the vessels, you gotta scale up the workforce. But that means you gotta burn a lot of money over a short period of time. The analogy that often gets used is: you are building the plane as you are flying it. Even though we haven’t figured out everything yet, we have to make it work as we go. It’s an incredible pace for the entire company.

How do you do maintain the different professional roles? What advice do you have for people who are at the beginning of their careers and looking to follow a similar path?
I operate one day a month and I have clinic one day a month, but the rest of my time is primarily dedicated to Humacyte activities while we are in this clinical trial. When I spoke with Duke’s leadership about taking the Humacyte CMO position as a sabbatical, they were fully supportive. They appreciated that we had the ability to translate something from its inception as a research project, to something that could eventually help save so many lives. Duke’s leadership understands the need for faculty to have time to innovate.

In terms of advice, there are three things I would say: First, when an opportunity comes around the corner and smacks you upside the head, don’t pass it up. For example, Laura (Niklason, co-founder of Humacyte) and I met by accident in the operating room and realized our research had a lot in common. She was trying to make a vascular tube and I was looking at endothelial function, and she was looking for someone to put cells in the tube, and we realized, we have a collaboration!

Secondly, I emphasize the importance of building teams with different domains – clinicians, researchers, engineers, regulatory specialists, et cetera. The whole really is stronger than the parts. By building a complementary team, we were able to successfully compete for one grant, followed by another, and another, to where we are now. Finally, never let your ego get in the way of a successful collaboration. We have had a longitudinal collaboration for 20 years that has transcended a lot of things – the concept of keeping your collaborators and your team, really goes a long way. It isn’t always about who’s last author, or who’s main PI on a grant, it’s about what the team can achieve.

The first human engineered blood vessel transplant was performed in 2013 – watch a short video featuring Dr. Lawson, Humacyte co-founder Dr. Laura Niklason, and the patient here (contains brief footage of surgical procedure). Interested in learning more about Dr. Lawson’s work? Check out this TedX talk: Engineered human-tissue blood vessels .

Resolving heart regeneration at the molecular level

Humans are incapable of sufficiently healing heart muscle after injury. Zebrafish on the other hand have a remarkable ability to regenerate their hearts. A new paper from the Ken Poss lab (Goldman et al, Developmental Cell, Feb 27, 2017) documents the development of a map of the zebrafish genome that gets activated during regeneration. This is the first such genome map produced for a regenerating tissue. From this map, postdoctoral researcher Aaron Goldman identified the genes and enhancers that are induced during regeneration. This map will help to unlock what is so special about the fishes’ ability to regenerate.

During regeneration, the types and proportions of cells within an organ change drastically. Thus, observed changes in gene activity can mask changes that are specific to regeneration. Since muscle is the most critical cell-type, Goldman used a novel technique to map genes and their enhancers from just the heart muscle of the fish rather than the whole heart organ. From this map we can begin to reveal the factors that are controlling required genes during regeneration. Molecules that are important to regeneration in fish will help guide and support therapies to achieve a similar result in humans.

Cardiac muscle cells in an uninjured zebrafish heart. Image courtesy Aaron Goldman.

Five Questions with Louis-Jan “LJ” Pilaz

In this continuing “Five questions with…” series, Sharlini Sankaran talks with Louis-Jan “LJ” Pilaz, Regeneration Next Postdoctoral Fellow from the Silver Lab at Duke, about his recently-published paper in the journal Current Biology.

What excites you about your work?
I have always been fascinated by the brain, this incredibly complex organic machine. The developing brain contains these cool radial glial cells that give rise to our “thinking units”, our neurons. But radial glial cells do so much more. They generate specialized brain cells such as astrocytes. They form a barrier between the brain and the rest of the body during development, and they also serve as a scaffold for migrating neurons.

They can do all this thanks to their unique morphology. Radial glial cells, are absolutely gorgeous and remain full of mysteries. I love to spend time thinking about them and I’m driven by the need to know more about them. Anything impacting their functioning can have devastating impacts on brain development and eventually lead to neurodevelopmental diseases. The more we know about them, the more likely we will be able to find cures for those diseases.

Can you describe the breakthrough discovery that led to the publication of this paper?

Click image to play a live video of messenger RNAs moving along the radial glial cell’s basal process. The messenger RNA can be seen as a bright spot moving from the bottom of the image to the top.

Radial glial cells bear two long protrusions, called processes, emanating from their cell body. These processes end with structures called “endfeet” because of the way they look. One of these processes spans the whole brain radially, going from the center outwards. It is called the basal process and ends with basal endfeet tightly connected to the “roof” of the brain. In the mouse the basal process can have a length of several hundred microns, in the human several millimeters. If the basal process is not properly maintained, neurons will not properly migrate to their final destination. If the connection between radial glial endfeet and the roof of the brain is altered, neurons will migrate too far away and will end up outside the brain. Despite the importance of those structures, little is known about what is going on inside them.

In our latest paper, we show that the basal process is a highway for molecular transport. We uncovered some fascinating functions taking place in the basal endfeet: we imaged messenger RNAs being transported at high speed from the cell body to the basal endfeet within living brain tissue (see video). With the help of Ashley Lennox, a graduate student in the lab, we showed that these basal endfeet RNAs can locally produce proteins, far away from the cell body. We discovered 115 different RNAs that accumulate in the basal endfeet. Importantly about 30% of those RNAs have been implicated in neurological diseases and might play a significant role during brain development. We also show that RNA transport may be influenced by FMRP, an RNA-binding protein linked to Fragile X Syndrome, the most common cause of autism caused by a mutation of a single gene.

Why is this discovery important to the field of regenerative medicine?
Neural stem cells receive a lot of attention in the field of regeneration in the nervous system. In some areas of the adult brain, stem cells and progenitors are still proliferating and differentiating. There is hope that one day we will be able to harness those neural stem cells already in place to produce neurons that were lost after a stroke or injury. Another strategy would be to grow neural stem cells in a dish and then introduce them into damaged brains to produce new neurons. Our paper uncovers completely novel mechanisms at play in radial glial cells. This is yet another piece of the neural stem cell “puzzle” that scientists need to consider when attempting either strategy to stimulate regeneration of injured or lost neurons in the brain.

Our paper establishes radial glial cells as a model of choice to study RNA localization and local protein production in distant areas of a cell. These two mechanisms are implicated in the regeneration of axons after injury. For that reason, future studies of RNA localization in radial glial cells may yield findings critical to better understand how it plays a role in the regenerating axon.

What comes next in this research?
Scientists do not know why radial glial cells spend so much energy to transport RNAs across such long distances and what that means for normal brain function. We are now actively trying to uncover the function(s) of those localized RNAs during brain development.

Is there anything else you want to share about your work?
I feel very fortunate to be working in Debby Silver’s lab and to be part of the Duke community. All this work would not have been possible without the support of core facilities and lively discussions with other labs. Duke is an amazing place to do science!

L-J’s work was recently featured in the Duke Med School Blog. You can read more about his discoveries here.

Mouse vouchers awarded to six investigators

house_mouseRegeneration Next supports expansion of animal models at Duke for the purposes of regenerative biology research. As such, RNI has awarded six new vouchers of up to $5,000 for new transgenic or genetically modified mice that will be used for tissue regeneration and/or stem cell research. The vouchers are redeemable for provision of services at the Duke School of Medicine Transgenic and Knockout Mouse Shared Resource. Congratulations to the PIs and their trainees!


  • Blanche Capel: Role of Lamin B Receptor in Male Germ Cell Differentiation and Epigenetic Regulation and Identification of Lamin Associated Domains During Male Germ Cell Differentiation and Epigenetic Programming Regeneration
  • Charles Gersbach: Generation of dCas9-­KRAB transgenic mouse line for screening of genes and enhancers during regeneration
  • Dwight Koeberl: Genome editing in a humanized mouse model of Pompe Disease
  • Ruorong Yan: Modulation of heart regeneration by enhancer-delivered factors
  • Eda Yildirim: Nucleoporin 153: Regulation of gene expression during specification of hematopoietic stem cell fate and
    embryonic development

The next callout for vouchers will be posted in early 2017 with an anticipated start date of June 1.

Duke PhD Students Win Grant to Study Science & Technology Policy Fellowship Feasibility in NC

Two Duke University PhD candidates have been awarded a $25,000 grant to study the feasibility of establishing a North Carolina Science and Technology Policy Fellowship Program. ccst-grant-award-featureThe California Council on Science and Technology (CCST) in partnership with the Gordon and Betty Moore Foundation and Simons Foundation is funding multiple grants to support planning processes for creating immersive science and technology policy fellowship programs in state legislature. The Fellowship Program would provide the state legislature with non-partisan science PhDs to assist them in grappling with the complex issues of science underlying many legislative initiatives.

Andrew George and Dan Keeley, researchers in the Duke Biology PhD program, won their bid for North Carolina with support from Science & Society, the Sanford School for Public Policy, the Duke Government Affairs Office, and the North Carolina Sea Grant Program. George and Keeley are mentored by Drs. Dave Sherwood and Dave McClay respectively. Sherwood is co-director of Regeneration Next and McClay is a Regeneration Next-affiliated faculty member. For more information on the grant>

Five questions with Michel Bagnat


Michel Bagnat

In this second installment of the series “Five Questions With,” Sharlini Sankaran talked with Dr. Michel Bagnat, Associate Professor of Cell Biology, about his recently announced selection as a prestigious Howard Hughes Medical Institute (HHMI) Scholar.

What excites you about your work?
Our work takes many months and when you first plan the research, you don’t always know how things are going to pan out. I get excited when we plan things well in advance, and everything falls into place when you see your research design work exactly how you expected. I find it exciting to make new tools that may later enable researchers to discover new mechanisms of regeneration and healing.

In our work, we get to open new directions for research, and we often see things come together in ways we were not anticipating. For example, we started off pursuing projects that were seemingly unrelated in the notochord (the zebrafish equivalent of the spinal cord) and intestine. We discovered some basic commonalities in the way the notochord and the intestine develop – it is exciting to see that


A cross-section of a zebrafish gut (image courtesy Bagnat Lab)

many systems are related, and understanding one may help in understanding of other systems.

What interests you about this particular area of regenerative biology?
Many of the basic biological processes we study happen to play a role in regeneration. I was interested in looking at basic biological process such as fluid secretion in various parts of the body. We know that in the intestine for example, tubes transport and secrete fluid, but we found that the same process of fluid transportation is responsible for also opening the lumen (gut) during zebrafish development. Basically, these cells secrete fluid that generates hydrostatic pressure that “pushes” lumen opening to form an intestinal tube during development. Hydrostatic pressure within a structure causes it to open and expand – picture a water balloon filling up and expanding.

In the notochord a similar process also takes place within lysosomes, large fluid-filled structures inside cells. These fluid-filled structures in the notochord were so big and so “there” that nobody looked at them, sort of like the elephant in the room. We found that a similar process, where lysosomes use hydrostatic pressure to “push” cells during morphogenesis (development of shape and structure), is also responsible for developing the shape and form of the notochord and the long axis of the trunk. We know that certain cells of the intestine also contain lysosomes with similar structural and genetic properties, but in the intestine these lysosomes play a different role: they are involved in nutrition rather than in morphogenesis.

Tell me about the breakthrough discovery that led to the HHMI award.
HHMI tends to fund a very diverse set of projects and investigators. I really don’t know exactly which discovery led to the award, but I can say that our work is very different than what other researchers are doing and I am grateful for the award.

Why is this work important?
The connections and similarities that we find along the way are important – we learn from these connections and can use them to find genes and mutations that are related to a human disease or condition. For example, we were studying the defects of intestinal barrier function in zebrafish and found a mutation that was related to regulation of a protein call TNF (tumor necrosis factor). Regulation of TNF is known to be a factor in irritable bowel syndrome in humans, so we looked for similar mutations in patients – and we found them.

The same thing happened when we were looking at notochord formation. We didn’t start out looking for a connection to scoliosis, but we found one. When we started studying lysosomes in zebrafish notochords, we found that certain genetic mutations cause impaired lysosome functions which cause the spine to be kinked. This is similar to what happens in scoliosis in humans.  Of course, there are many other factors involved in scoliosis, but this finding brings us closer to an understanding of what could cause it.

What comes next for you?
Every time we look into a basic problem, we end up finding new ones. Our work in both areas has opened up new research questions we want to pursue further. The difficulty for us is that the research tools to enable the work we want to do are not there, and we have to make them as we go. I don’t think my lab has ever worked on anything that has already been established!

On one hand it is exciting and an advantage to be the first to accomplish something in the field. But on the other hand, it is harder to get other people excited about work that is so new.  I hope that as we progress in our work, other researchers will get excited and contribute to understanding of the connection between developmental processes, disease, and regeneration.

Five questions with Mayssa Mokalled


Dr. Mayssa Mokalled

We are beginning a new feature called “Five Questions” to highlight breakthrough research and achievements in regeneration research in Duke. Sharlini Sankaran talked with Dr. Mayssa Mokalled, a postdoctoral fellow in Ken Poss’ lab, about her newly-published paper in the journal Science.

1.       What excites you about your work?
How could the spinal cord be rebuilt after injury or disease? How could function be regained after paralysis?  Why can zebrafish regrow their spinal cord, but not mammals? These are the big questions that keep me excited about my work. At the same time, the experimental aspects of my work keep me excited on a day-to-day basis. Overall, I feel privileged that my research is truly my most favorite hobby. I enjoy having the intellectual freedom to ask the questions I am most excited about, the significance and potential applications of making biological discoveries, and the continually renewed excitement about the next questions.

A zebrafish spine in the process of self-healing. The green indicates the bridging glial cells during regeneration.

A zebrafish spine in the process of self-healing. The green indicates the bridging glial cells during regeneration.

2.       Tell me about why you chose to study zebrafish regeneration.
Having trained as a developmental biologist and mouse geneticist, I have a fascination for the questions and possible applications of tissue regeneration.  Intrigued by the uneven distribution of regenerative capacity across species, I decided to investigate a regenerative model system.  As a highly regenerative, vertebrate, genetic model organism, zebrafish were the obvious choice.  Joining the Poss lab was an unmatched opportunity to train in adult zebrafish regeneration. My long-term plan is to gain expertise and knowledge of the zebrafish model system to understand the bases for the differential regenerative capacity between zebrafish and mammals.

3.       Briefly describe your breakthrough discovery that led to the publication of this paper.
Our goal is to explore what enables spinal cord regeneration in zebrafish. To do this, we identified the connective tissue growth factor (ctgfa) gene, and activated it in zebrafish with complete spinal transections.  Characterizing the expression and function of ctgfa during spinal cord regeneration revealed a number of findings that led to the publication of this paper. We found that ctgfa expression marks the bridging glial cells that connect the severed cord. Functionally, ctgfa is a pro-regenerative factor that is necessary and sufficient to stimulate regeneration and functional recovery after spinal cord injury.

4.       Why is this discovery important to the field of Regenerative Biology?
Developing means to treat and reverse spinal cord injury is a pressing need in regenerative medicine. Zebrafish glial cells display a unique, yet poorly understood, bridging response that could account for their remarkable regenerative capacity. Our findings present a major step towards understanding the mechanisms of glial bridging.  We generated fundamental discoveries about how zebrafish regrow their spinal cord – we now have a model that we can use to further explore how to boost the regenerative potential of the mammalian spinal cord.

5.       What comes next in this research?
Our findings stimulated a number of directions that we are eager to pursue. In the course of our work, we generated unique tools to further investigate the mechanisms of spinal cord bridging in zebrafish.  A natural future direction for our study is to characterize the expression and function of the ctgf gene after mammalian spinal cord injury.  Identifying the type of glial cells that can produce CTGF or are competent to respond to it could inform new methods to repair the mammalian spinal cord after injury.

Mayssa’s work has been featured in international news outlets and science blogs. Read more about this groundbreaking work here and here.