Opening my eyes to research

 A guest blog by Dorothea McGowan
Ms. McGowan is a Regeneration Next Summer Research Fellow in the MacLeod lab at Duke’s Department of Dermatology. In this guest post, she shares her experiences and insights from her first research experience.

Dorothea McGowan

On the morning of March 27th, I received an email from Duke University stating I had been accepted to Regeneration Next Summer Fellows program. I immediately felt an onset of emotions. I was beyond ecstatic to be accepted, but was terrified of what would await me. I was a third-year Public Health student graduating a year early and had no previous lab experience. Despite my fears, I decided to accept the fellowship and see how I could grow academically and mentally.

I had many preconceived notions about Duke being an exceedingly competitive field with a cut-throat environment. But I have found out in my time here, that this is simply not true. What I have experienced, is that the research labs are full of some of the world’s most brilliant researchers, but they are also full of the most gracious and accommodating researchers.

Research is an essential aspect of Duke’s fundamental principles; in fact, medical students at Duke participate in a whole year of research as third-year students. Incorporating research into the medical school program allows students to grasp the foundations of research and genuinely understand the work behind the science that they will practice on a daily basis as physicians.

Dorothea (2nd from right) with Dr. Amanda MacLeod (back row, right) and members of the lab. Photo courtesy MacLeod lab

My summer research experience is in the MacLeod lab, which focuses on the mechanisms of Skin Immunity. As a Public Health major my curriculum only briefly focused on the hard sciences, so this was a very new and intimidating experience. Despite my own preconceived notions of feeling intimidated and doltish, I was welcomed into a lab with an extremely conducive learning environment. I felt that I could always ask questions when I needed help and that I always received sincere explanations to the questions I asked. Every lab member has treated me with the utmost respect and patience which has stimulated my own drive to gain as much knowledge as possible. I never once have felt like I wasn’t welcomed in the lab, and that is an essential aspect of creating an encouraging learning environment.

Dr. Amanda MacLeod is not only a brilliant researcher, she is also a compassionate and generous leader of her research laboratory. Dr. MacLeod’s adaptable nature allows her to connect with everyone that sets foot in her lab as well as mentor each person in a way that best fits their own particular way of learning. Dr. Macleod is not just an example of what it means to be a great leader, but sets the standard of what all leaders should want to exemplify. Creating an environment that not only produces top of the line research but also demonstrates an exceptional learning environment is something most people aspire to do, and the MacLeod lab does that with ease.

Before coming to Duke I was sure that Dermatology was the specialty I would pursue in residency, but now I am interested in a variety of specialties. The MacLeod lab has allowed me to see  how different fields of medicine work together to uncover solutions to disease. That has really opened my eyes to other specialties like infectious disease and emergency medicine. It is nice to see that no matter what specialty you chose you can still do research as a PI or a collaborator. Over the past few weeks my own determination to pursue an MD has not wavered but I am now more open to the vast number of specialties and research topics that there are to pursue.

This experience will help me get into medical school. My eyes are opened to a different type of research compared to the research I did as a Public Health professional because of this program. This program has shown me the fundamentals of medical research and allowed me to understand a more quantitative side of research. This will not only be helpful for getting into medical school but will also be helpful when doing research within medical school.

Although my time at the MacLeod lab has been brief, I am able to understand why the researchers produce such quality work as the environment in the lab is a superb teaching and learning environment for all. As my summer progresses, I hope to learn more about how the research done here applies to a whole world perspective. During the end-of-summer presentation on August 3rd, I hope to be able to clearly explain my project to my peers with confidence that I was able to comprehend the process and results well enough to convey them to an audience.

Gene Therapy moves up the road to Duke

Gene therapy moves up the road to Duke
From Regeneration Next Director, Ken Poss, Ph.D.:

On behalf of the Regeneration Next Initiative, I’m excited to welcome Aravind Asokan, Ph.D., to Duke University. This August, Aravind moves up the proverbial “8 mile rivalry road” from UNC to join Duke University as the School of Medicine’s Director of Gene Therapy in the Department of Surgery. Asokan will also be an affiliate of the Regeneration Next Initiative and hold appointments in Molecular Genetics & Microbiology and Biomedical Engineering.

A central goal of our Initiative is to strengthen our community of researchers in tissue regeneration, and the recruitment of Aravind was a wonderful example of Duke teamwork toward that goal. Regeneration Next was key in recruiting Aravind to Duke, and we are grateful to Dean Klotman and leadership in various School of Medicine units who partnered with us to make his recruitment a success.  

The future of regenerative medicine is targeted delivery of molecular factors to stimulate healthy tissue regeneration. Having Aravind as our colleague will galvanize efforts here at Duke to develop and apply gene therapy vectors in research models, and ultimately as a means to deliver regenerative therapies. As you’ll read below, gene therapy holds enormous promise to transform how we treat conditions of tissue damage or loss such as diabetes, myocardial infarction, neurodegenerative disease, and joint disease.

Regeneration Next’s Executive Director Sharlini Sankaran, Ph.D., sat down with Asokan for an interview.

Aravind Asokan photo

Aravind Asokan, Ph.D, Director of Gene Therapy at Duke University. Image courtesy Aravind Asokan.

SS: What excites you about your work?
AA: If I had to sum it up in one word, it would be: “Discovery.” You can take things that are in nature, for example viruses, and be able to tweak them, improve them, and discover new functionalities. That’s really the most exciting part of what we do. There’s just a lot of things we learn along the way. For example, in the case of gene therapy, we are able to engineer these viruses so they are useful, and you can use them to address challenges and questions that are being raised in the clinic.

SS: What is gene therapy?
AA: The rationale behind gene therapy is [that] the root cause of many of these diseases is at the genetic level. We understand some of them well, for instance, monogenic diseases where you have a mutation in a particular gene. In its simplest form, having a mutation in a single gene makes that gene nonfunctional and as a consequence there is an insufficiency of a critical protein coded for by that gene. So, how do you supplement that protein back in the patient?

What gene therapy does is address this in one of two ways: either provide the correct copy of the gene so that you can supplement the protein that needs to be made, or you can go in and edit the gene. In another scenario, perhaps the mutated gene product is toxic and needs to be silenced.

So no matter what modality you are looking at – whether it is gene replacement, gene editing, or gene silencing – essentially gene therapy is delivering the tools or the information that is going to correct that situation, in the form of DNA.  The genetic material is the “cargo” and the virus is the “delivery vehicle.”

SS:  Can you give me one example of a clinical question that you can answer in your research?
AA: We want to translate what we are finding in nature, and design it in a different way, to be useful in the clinic. So taking an example that focuses on the brain, one challenge in the neurology space we have tackled is – how do you get enough of the genetic material you are trying to deliver to enter the brain? In other words, how do you get these tools (viruses) effectively across the blood-brain barrier?

We tackled this problem by looking at some naturally primate-derived viruses that are able to cross the blood-brain barrier, then we learned the structural cues that allow them to get across. Once you find those out, you are able to graft those onto other “cousins” of these viruses and get those to cross the blood-brain barrier too. In other words, it’s like a bar code that you discover and can slap on to these viruses, that allows them to get across the blood-brain barrier and deliver the desired genetic material to targeted areas in an effective manner.

3D model of an engineered AAV

3-D model of a synthetic AAV capsid evolved in the Asokan lab. The different colors represent newly engineered footprints on the viral capsid surface that serve as barcodes for evading antibodies, homing to specific tissues, entering cells and delivering the genetic cargo. Image courtesy: Aravind Asokan

SS: Can you explain how gene therapy could help treat some common conditions?
AA: Gene therapy has already been approved for treatment of a couple of diseases. The most recent one is a currently available product called Luxturna, which treats a form of congenital blindness. Essentially there is a mutation in a gene called RPE-65, which is known to be responsible for a condition called retinitis pigmentosa. Luxturna is a gene therapy treatment that provides a correct copy of the gene to treat this congenital disease.

Other gene therapy treatments that look promising and hopefully poised for FDA approval in the near future are those for spinal muscular atrophy, musculoskeletal disorders, and hemophilia. These trials are all moving forward at a fast clip and I think we are at the cusp of this paradigm shift we are going to see, where viruses carrying therapeutic DNA cargo are going to become a form of medical treatment.

SS: What needs to happen before gene therapy becomes a widely-accepted and safe treatment available to patients?
AA: Clinical trials and preclinical studies in the field have taught us that there are three levels at which we should look at safety aspects of gene therapy.

First, at the virus level, it’s really important to understand that while the viruses are derived from non-human primate sources, or are novel viruses that are engineered in labs, none of them carry their own DNA; they are only shells that carry the therapeutic genetic material. So, understanding the properties of the viral protein shell and its interactions with the host are important.

At the second tier of safety: what does the DNA cargo do? There is a question of genotoxicity – can the material integrate into different regions in the genome leading to unwanted consequences? For instance, could the cargo accidentally turn on genes that were off or vice versa.? In case of the virus that I work with, the AAV or adeno-associated virus, the clinical safety profile in this regard has been good. One of the reasons is that this virus doesn’t tend to integrate its therapeutic cargo into our DNA very effectively. It actually ends up closing in on itself to form a mini circle, which persists on its own. There are several groups working to further understand and improve the safety profile of these already safe viruses.

The third safety aspect is the potential for immunotoxicity. We all have immune responses to viruses and foreign proteins that are presented to our immune system. In some cases of patients with rare diseases, they have a mutation or deletion of a gene so the protein is not made at all. When you introduce this protein through gene therapy, these patients’ bodies are seeing that protein for the first time and that may trigger an immune response. The immune responses to gene therapy that we have seen in clinical trials have been moderate thus far, and have been addressed by anti-inflammatory steroids. But, there are nuances about the immunological aspects that we are only just beginning to understand and the hope is to continue to improve the safety profile on all fronts.

SS: Which areas can we expect to see expansion of gene therapy applications?
AA: From a single-gene, rare-disease genetic disorder, “let’s provide a copy of this gene” approach, there are a couple of approved products already with more on the horizon for this year and next year. So it’s really going to take off on that front, as far as the next class of medicines that are going to be approved. There are all these new paradigms that are going to be really exciting to explore as we expand the scope of gene therapy.

SS:  How does the strong community of regeneration researchers at Duke factor into your future research plans?
AA: The exciting long-term research breakthroughs are going to be: where else can we use this [gene therapy] approach? For instance, can we use these viral tools successfully for genome editing?  Can we expand past monogenic diseases? For example in regenerative medicine, could we genetically manipulate tissues of interest then use them for transplantation into patients? Or are we going to be able to manipulate tissues in situ and reprogram tissues to regenerate?

I have my whole crew, we are just moving across I-40 and up 15-501. We’re hoping to hit the ground running and have already engaged in active discussions with folks at Duke that we are really excited about.  Expanding into the regenerative medicine aspect of research is something we’ve all talked about, particularly in the cardiac space, and there is quite a bit of excitement in my lab about getting started on this new journey at Duke.

SS: What are you most looking forward to as you begin a new chapter at Duke?
AA: One thing I appreciated during my recruitment to Duke is that there are a LOT of people and departments who plugged into the process. It started as conversations with Charlie Gersbach (Biomedical Engineering) and Bruce Sullenger (Surgery). And from there, Priya Kishnani (Pediatrics) in the Alice and Y.T. Chen Center for Genetics and Genomics and other folks in Neurology and Molecular Genetics & Microbiology (MGM) were plugged in. Ken (Poss) of Regeneration Next and then Allan Kirk (Surgery) drove the whole process to fruition thereafter.

I have been actively seeking opportunities this past academic year. To other institutions’ credit, they all have their strengths, wonderful people and some amazing programs. But the spectrum of research and the collaborations at Duke excited me the most.

One of the things I am most excited about is the spectrum of folks that I am going to be able to work with. I think this is unprecedented: the critical mass that can be generated by establishing cross cutting applications of our work can enable everything from developmental biology to gene therapy and genome editing.

“Can broken hearts be mended?” – Interview with Ken Poss

The International Journal of Developmental Biology’s recent special issue on Regeneration Biology features an interview with Regeneration Next’s director, Ken Poss.

In 2002, Poss discovered that zebrafish can regenerate heart muscle after injury, leading to a new line of research on heart regeneration. The Poss laboratory has spearheaded findings that reveal concepts and mechanisms of regeneration in zebrafish heart, fin, and spine. Poss has recently shown that innate mechanisms of regeneration can be successfully stimulated in neonatal mouse hearts as well.

In the interview, Poss shares his thoughts on people who inspire him, the main goals in today’s regeneration research, and the implication of this research for future human health treatments. The full interview can be accessed here (PDF).

New video: Unlocking joint and muscle tissue regeneration

From gene editing to stimulating the body’s innate mechanisms of tissue repair, Duke scientists and engineers are tackling different ways to someday provide treatments for patients with injury or degeneration of musculoskeletal tissues.

Watch this brief video which features Drs. Ben Alman, Shyni Varghese, and Charlie Gersbach of Regeneration Next. Each researcher is working on a strategy that could help us get closer to a regenerative medicine-based treatment for bone or joint tissue damage.

Congratulations, RNI travel grant winners!

Regeneration Next is pleased to announce seven travel awards to assist graduate students in traveling to scientific conferences. The students will present tissue regeneration-related work in a variety of different research areas, at national and international conferences. This is the third cycle of travel grants supported by Regeneration Next. Read about the winners of Cycle One and Cycle Two to see what we’ve supported in the past. The next deadline for applications is September 17, 2018. Details are here>

The winners of the Regeneration Next travel awards are:

  • Emily Bowie, Goetz lab. “Primary cilia regulation of adult neuron homeostasis,” presenting at the EMBO Workshop – Cilia meeting in Copenhagen, Denmark.
  • Caley Burrus, Eroglu lab. “Striatal projection neurons require huntingtin for synaptic connectivity and longevity,” presenting at the Gordon Research Conference on Cellular and Molecular Neurobiology in Hong Kong.
  • Woonyung Hur, DiTalia Lab. “Cyclin-dependent 2 driven phase separation regulates histone locus body assembly,” presenting at the Cell Cycle Meeting in La Jolla, California.
  • Fei Sun, Poss lab. “Organ crosstalk during cardiac regeneration in zebrafish,” presenting at The Molecular and Cellular Basis of Tissue Regeneration and Repair meeting in Malta.
  • Susan Wopat, Bagnat lab. “Spine patterning is guided by segmentation of the notochord sheath,” presenting at the International Zebrafish Conference in Madison, WI.
  • Albert Zhang, Yan Lab. “The regulation of gliogenesis in C. elegans by lin-32,” presenting at the Gordon Research Conference on Cellular and Molecular Neurobiology in Hong Kong.
  • Hazel Zhang, Alman lab. “Role of glutamine metabolism in cartilage tumors,” presenting at the Gordon Research Conference on Bone and Teeth in Galveston, TX.

How Gut Walls Get their Wave

Reposted from Duke Research Blog

The walls of our guts are lined with finger-like protrusions called villi (green), which absorb nutrients from our food, and pockets called crypts (purple), which provide homes to stem cells. Duke cellular biologist Kaelyn Sumigray wants to know how the crypts get their pitted shape. In a new study on mice, she found that specific genes direct rows of cells to constrict on one side and expand on the other, forming curves in the intestinal wall like the bending of a slinky. Understanding how these crypts form will help researchers figure out their role in nurturing adult stem cells.

https://www.cell.com/pb-assets/journals/research/developmental-cell/Meet%20the%20Author/sumigray.jpgThis gorgeous image comes from a recent paper, published May 3rd, in the journal Developmental Cell, describing Dr. Sumigray and her colleagues’ findings about how gut crypts form.

The journal also featured a Meet the Author Q&A about Dr. Sumigray. You can read more about Dr. Sumigray and what motivates her research in this interview here>

Regeneration Next Postdoctoral Fellows – 2019-2021

We are thrilled to announce our Regeneration Next Postdoctoral Fellows, 2019- 2021! This impressive third cohort consists of four Fellows chosen from a competitive pool of fifteen applicants. Their research interests are wide, ranging from liver regeneration, to bone formation, to nervous system repair and the mechanisms behind ALS (Lou Gehrig’s disease). They join the inaugural cohort and the 2018 – 2020 Fellows in shaping and growing the tissue regeneration community at Duke University. Congratulations to all of them!

Mariah Hoye, Ph.D.
Mariah Hoye received her PhD from Washington University in Saint Louis, MO where she studied the role of small, non-coding RNAs in motor neurons and their relation to the motor neuron degenerative disease, Amyotrophic Lateral Sclerosis (ALS). For her postdoctoral training, she will be working in the laboratory of Dr. Debra Silver in the Molecular Genetics and Microbiology department at Duke. As an RNI fellow, Mariah seeks to understand the RNA metabolism of neural stem cells that is required for proper brain development and how aberrations to stem cell RNA metabolism can lead to neurodevelopmental disorders and brain cancers.

Guoli Hu, Ph.D.
Guoli received his PhD in Cell Biology at Shanghai Jiao Tong University, in China. He recently accepted a postdoctoral associate position in the Department of Orthopaedic Surgery at Duke’s School of Medicine, where he works in Dr. Courtney Karner’s lab. His current research focuses on understanding the role of glutaminase (GLS) in regulating mesenchymal stem cell specification and differentiation into osteoblasts. With the support of the Regeneration Next Fellowship, he plans to further investigate whether stimulating GLS dependent glutamine catabolism is a potential osteoanabolic strategy for bone formation and regeneration in pathological osteoporosis and fracture healing.

Jeongeun Hyun, Ph.D.
Jeongeun received her Ph.D. degree in Integrated Biological Science at the Pusan National University, in South Korea, where she studied post-transcriptional regulation of microRNAs during trans-differentiation of hepatic stellate cells and the therapeutic role of microRNAs in liver fibrosis, under the supervision of Dr. Youngmi Jung. She recently joined the laboratory of Dr. Anna Mae Diehl in the Department of Medicine,  where she is investigating the role of RNA-binding proteins as important gene regulators in control of cellular plasticity during adult liver regeneration and in clinically relevant liver disease. As an RNI fellow, she aims to identify the native mechanisms that can be manipulated to improve recovery from liver injury, and specifically by preventing excessive accumulation of myofibroblastic hepatic stellate cells.

Francesco Paolo Ulloa Severino, Ph.D.
Francesco conducted his PhD studies in Neurobiological Sciences at ISAS, Trieste, Italy, under the mentorship of Prof. Vincent Torre. Francesco is  fascinated by the mechanisms that nature uses to develop and shape the central nervous system. He wants to investigate the cross-talk between neurons and glial cells that underlies proper brain function. He is also interested in developing and applying advanced imaging and physiological technologies to investigate and repair the nervous system. Francesco will be jointly mentored during his RNI Fellowship by Drs. Cagla Eroglu (Cell biology) and Henry Yin (Neurobiology) to study how manipulation of astrocytic function could help recover motor functionality under disease conditions such as Huntington’s disease

Scientists Find Stomach Cells in Lung Cancer

This post originally appeared on Duke Today and is reposted here with permission.

New research from Duke has found that some lung cancer cells with errors in transcription factors begin to resemble their nearest relatives – the cells of the stomach and gut. (Credit – Tata Lab, Duke University)

DURHAM, N.C. – Tumors are notoriously mixed up; cells from one part often express different genes and adopt different sizes and shapes than cells from another part of that same tumor.

Still, a team of researchers were surprised when they recently spotted a miniature stomach, duodenum, and small intestine hidden among the cells of lung tumor samples.

They discovered that these cells had lost a gene called NKX2-1 that acts as a master switch, flipping a network of genes to set the course for a lung cell. Without it, the cells follow the path of their nearest developmental neighbor — the gut — much like a train jumping tracks when a railroad switch fails.

The findings, published March 26 in the journal Developmental Cell, underscore the amazing resilience and plasticity of cancer cells. Such plasticity can presumably enable tumors to develop drug resistance, arguably the biggest challenge to successful cancer treatment.

“Cancer cells will do whatever it takes to survive,” said Purushothama Rao Tata, Ph.D., lead study author and assistant professor of cell biology at Duke University School of Medicine and a member of the Duke Cancer Institute. “Upon treatment with chemotherapy, lung cells shut down some of the key cell regulators and pick up the characteristics of other cells in order to gain resistance.”

Tata has spent most of his career studying the cell types that make up normal lung tissue and how these cells display flexibility during regeneration following an injury. Tata began to wonder whether some of the same rules that he had found governing the normal development and regeneration of tissues might also be responsible for the jumbled nature of tumor cells.

He decided to focus on non-small cell lung cancer, which accounts for 80 to 85 percent of all lung cancer cases. Lung cancer is the leading cause of cancer deaths worldwide, and has one of the lowest survival rates among all cancers. Tata analyzed data from the Cancer Genome Atlas Research Network, a large consortium that has profiled the genomes of thousands of samples from 33 different types of cancer. He found that a large proportion of non-small cell lung cancer tumors lacked NKX2-1, a gene known to specify the lung lineage. Instead, many of them expressed a number of genes associated with esophagus and gastrointestinal organs.

In the absence of NKX2-1, Tata hypothesized, lung tumor cells would lose their lung identity and take on the characteristics of other cells. Because during development lung cells and gut cells are derived from the same parent, or progenitor, cells, it made sense that once the lung cells lost their way they would follow the path of their nearest developmental sibling.

To test whether this was the case, Tata and his colleagues generated different mouse models. First, they knocked out the NKX2-1 gene in the lung tissue of mice. Under the microscope, they noticed features that normally only appear in the gut, such as crypt-like structures and gastric tissues. Amazingly, these structures produced digestive enzymes, as if they resided in the stomach and not the lung.

Having shown that a simple genetic tweak could prompt lung cells to switch developmental tracks, Tata wondered if another tweak or two could fuel them to form tumors. This time, in addition to knocking out NKX2-1, they activated the oncogenes SOX2 or KRAS. The team found that mice with the superimposed SOX2 mutations developed tumors that looked as if they belonged in the foregut; those with KRAS mutations developed tumors that resembled parts of the mid- and hindgut.

Tata and colleagues then wanted to know if these genes were sufficient to alter the fate of lung cells, or if they needed additional signals from their native microenvironment. To answer this question, they developed a novel “mini-lung tumoroid” system — miniaturized versions of lung tumor tissue — and found that manipulation of genetics was enough for the lung cells to show such plasticity.

“Cancer biologists have long suspected that cancer cells could shape shift in order to evade chemotherapy and acquire resistance, but they didn’t know the mechanisms behind such plasticity,” said Tata. “Now that we know what we are dealing with in these tumors – we can think ahead to the possible paths these cells might take and design therapies to block them.”

In the future, Tata plans to use his mini-lung tumoroid system to further explore the mechanisms of resistance in lung cancer cells.

This research was supported by the New York Stem Cell Foundation, the National Institutes of Health/National Heart, Lung, and Blood Institute Early Career Research New Faculty (P30) award (5P30HL101287-02) and RO1 (RO1HL118185), the Harvard Ludwig Cancer Center, the Massachusetts Eye and Ear Infirmary, a Harvard Stem Cell Institute Junior Investigator Grant, an NIH MSTP training grant (T32GM007205), the Medical Scientist Training Program (GM007101), an NIH/NHLBI Career Development Award (K99HL127181), the Whitehead Scholar Program, the Maroni Research Scholar Program, and the HHMI Faculty Scholar Program.

CITATION: “Developmental History Provides a Roadmap for the Emergence of Tumor Plasticity,” Purushothama Rao Tata, Ryan Dz-Wei Chow, Srinivas Vinod Saladi, Aleksandra Tata, Arvind Konkimalla, Anne Bara, Daniel Montoro, Lida P. Hariri, Angela R. Shih, Mari Mino-Kenudson, Hongmei Mou, Sioko Kimura, Leif W. Ellisen, Jayaraj Rajagopal. Developmental Cell, March 26, 2018. DOI: 10.1016/j.devcel.2018.02.024

Honoring Dr. Brigid Hogan

Dr. Brigid Hogan, Chair, Duke Cell Biology Department

Distinguished developmental biologists from just down the hall and as far away as Singapore, Japan, and England convened at Duke on Friday, March 9, for a special symposium on Developing the Mouse Embryo. Speakers at the symposium highlighted breakthroughs in cell and developmental biology and implications for human health. The day-long event was a celebration of Dr. Brigid Hogan, Chair of Duke University’s department of Cell Biology. Dr. Hogan is a world leader in developmental biology and stem cell research, and in 2002 was the first woman to be appointed as Chair of a basic science department at Duke University.

Ken Poss, Director of Duke’s Regeneration Next Initiative and Professor of Cell Biology, said, “Brigid has shown remarkable leadership for fifteen years as Department Chair. We all appreciate her vision and her support of the field, as well as her groundbreaking work in developmental biology.”

Dr. Richard Behringer, Professor of Genetics at University of Texas’ MD Anderson Cancer, was a presenter at Friday’s symposium. Dr. Behringer wrote a blog post about the Symposium on the Developmental Biology website, The Node. He recounted that many people shared touching “Brigid stories” showing how Dr. Hogan has inspired a generation of biologists. Dr. Behringer’s blog post is reposted below.

Last Friday March 9, a research symposium was held at Duke University in Durham, North Carolina to honor the career and retirement of Professor Brigid Hogan, Chair of the Department of Cell Biology. Current and former Hogan Lab members, colleagues, and friends came from across America, Japan, and the United Kingdom to join in the celebration of a truly remarkable scientist. There were 14 invited speakers, including former students, postdocs, colleagues from Brigid’s days at Vanderbilt University in Nashville, Tennessee, current members of the Department of Cell Biology at Duke, and friends in the mouse development and genetics field. More than 150 participants that included local students and postdoctoral fellows came to hear outstanding research talks. Among the participants, luminaries in the mouse developmental biology field were there to honor Brigid, including Gail Martin, Liz Robertson, Liz Lacy, Frank Costantini, Phil Soriano, Terry Magnuson, Blanche Capel, Kat Hadjantonakis, and Mary Dickinson. The symposium started with surprise videos from friends Fiona Watt (King’s College London) and Jim Smith (Francis Crick Institute), sending their congratulations to Brigid and one from Brigid’s third graduate student, Peter Holland (University of Oxford), praising her skills at inspiring his confidence as a young scientist during his thesis research. The research talks discussed current research, including gene regulatory networks, cutting-edge microscopic imaging, organogenesis, the genetic basis of human disease, novel gene manipulation approaches, embryos on a chip, organ-specific stem cells, high-throughput mouse mutant phenotyping, and tissue regeneration. The talks highlighted the advances in the field of cell and developmental biology and why this area of research is so important for basic knowledge and human health. To learn more about Brigid’s background and motivation to study mouse embryos and organs see her 2015 interview with The Node (http://bit.ly/2DqfZiM).

In addition, to the wonderful science that was presented that day, all of the speakers had a “Brigid story” that they shared with the audience. Many spoke of her drive, curiosity, generosity, patience, and for those who were trained in her lab, the lessons they learned from her. These included ‘don’t talk yourself out of an experiment, sometimes you just have to do it’, ‘be brave’, ‘finish what you start’, ‘speak up and speak out’. My favorite was ‘don’t apologize for being a tall, confident woman’. Everyone praised Brigid’s skills as a mentor. You can read about Brigid’s thoughts on mentoring in a recent interview in Cell Stem CellMentoring the Next Generation (http://bit.ly/2Dk1PiM). Yes, Brigid is “retiring” but she will still be very active. At the end of the symposium, Brigid thanked everyone for attending and participating, especially those who traveled such long distances. She said it brought “a joy to my heart” and was a “day I’ll always remember”.

Reposted from the Node, March 13, 2018 with permission.

How A Zebrafish’s Squiggly Cartilage Transforms into a Strong Spine

Blog post by Kara Manke. This article first appeared on the Duke Research Blog, and is reposted here in its entirety.

Our spines begin as a flexible column called the notochord. Over time, cells on the notochord surface divide into alternating segments that go on to form cartilage and vertebrae.

In the womb, our strong spines start as nothing more than a rope of rubbery tissue. As our bodies develop, this flexible cord, called the notochord, morphs into a column of bone and cartilage sturdy enough to hold up our heavy upper bodies.

Graduate student Susan Wopat and her colleagues in Michel Bagnat’s lab at Duke are studying the notochords of the humble zebrafish to learn how this cartilage-like rope grows into a mature spine.

In a new paper, they detail the cellular messaging that directs this transformation.

It all comes down to Notch receptors on the notochord surface, they found. Notch receptors are a special type of protein that sits astride cell membranes. When two cells touch, these Notch receptors link up, forming channels that allow messages to rapidly travel between large groups of cells.

Notch receptors divide the outer notochord cells into two alternating groups – one group is told to grow into bone, while the other is told to grow into cartilage. Over time, bone starts to form on the surface of the notochord and works its way inward, eventually forming mature vertebrae.

When the team tinkered with the Notch signaling on the surface cells, they found that the spinal vertebrae came out deformed – too big, too small, or the wrong shape.

Meddling with cellular signaling on the notochord surface caused zebrafish spines to develop deformities. The first and third image show healthy spines, and the second and fourth image show deformed spines.

“These results demonstrate that the notochord plays a critical role in guiding spine development,” Wopat said. “Further investigation into these findings may help us better understand the origin of spinal defects in humans.”

Spine patterning is guided by segmentation of the notochord sheath,” Susan Wopat, Jennifer Bagwell, Kaelyn D. Sumigray, Amy L. Dickson, Leonie F. Huitema, Kenneth D. Poss, Stefan Schulte-Merker, Michel Bagnat. Cell, February 20, 2018. DOI: 10.1016/j.celrep.2018.01.084