Space: The Cardiac Frontier

A guest post by Arun Sharma

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Arun Sharma speaks at a NASA press conference. (Photo credit: NASA/Kim Shiflett)

My passions for the very large (outer space) and the very small (stem cells) came together in ways that I could have never predicted this summer when I sent patient-specific, beating human heart cells, to the International Space Station aboard a SpaceX Falcon 9 rocket. As mankind spends more time in space, with the imminent goal of traveling to Mars, we need to better understand how human cells function in a nearly weightless, or microgravity, environment. Recent scientific advances have made it possible to mass-produce long-lasting, stable human heart muscle cells (cardiomyocytes). My colleagues and I have spent several years working to generate these cells from stem cells, and our efforts paid off when we recently sent a sample of cardiomyocytes to the International Space Station to study cardiac function.

My interest in cardiovascular regenerative medicine was born when I was an undergraduate student at Duke University, after learning about the work being conducted in the labs of Dr. Ken Poss and Dr. Gerry Blobe. I devoted myself to cardiovascular regenerative medicine, trying to understand ways that the human heart might be able to restore lost cells similarly to how a zebrafish can regrow heart muscle. At Duke, I was fascinated to learn about induced pluripotent stem cells (iPSCs), a type of stem cell derived directly from adult cells. I could see the potential that these cells hold to treat cardiovascular disease. At the Harvard Stem Cell Institute’s summer internship program, I got my first hands-on experience with making beating cardiomyocytes from iPSCs.

My summer stem cell experience, while exhilarating, left me thirsting for more. So, I enrolled in the Stanford University’s new PhD program in Stem Cell Biology and Regenerative medicine. Over the past four years at Stanford, I have devoted my scientific studies to making stable, long-lasting cardiomyocytes from iPSCs. With this new cell system, we can better model cellular changes in the human cardiomyocyte’s response to microgravity.

Astronaut Dr. Kate Rubins changes nutrients for space-flown iPSC-CMs. (Photo credit: Arun Sharma)

Astronaut Dr. Kate Rubins changes nutrients for space-flown iPSC-CMs. (Photo credit: Arun Sharma)

In the past few months, I have had the chance to interact with astronauts, aerospace engineers, and fellow biologists, all of whom are passionate about space science and understanding how the human body functions in space. With the aid of biologist and astronaut Dr. Kate Rubins, who is currently aboard the International Space Station, we have been able to examine iPSC-cardiomyocyte changes in form and beating rate using short video clips taken aboard the station’s light microscopy module. Dr. Rubins also preserved a small sample of cells for gene expression analysis and “fed” the cells to keep them healthy. Another sample of cells was recently returned to us alive, and I’m happy to say, they are still beating. Heart cells are certainly tough, even in the face of adverse conditions such as low gravity!

We are very excited to see what our further analyses of these space-flown heart cells will reveal. Our studies may uncover novel insight into how the heart functions in a unique environment such as microgravity, and hopefully, our work can aid humanity as it pushes further into the stars. Ultimately, my experience this summer would not have been possible without the opportunities I had at Duke almost a decade ago that led me down the path towards a career in regenerative medicine. The sky is not the limit for regenerative medicine at Duke University!

Beating heart cells aboard the International Space Station (Courtesy Arun Sharma)

Beating heart cells aboard the International Space Station (Courtesy Arun Sharma; click to play)

Arun Sharma (Duke Trinity Class of 2012) holds the BS from Duke University and is currently a PhD student at the Stanford University Stem Cell Biology and Regenerative Medicine program under the mentorship of Drs Sean Wu and Joseph Wu. He is a graduate of the Harvard Stem Cell Institute’s Summer internship program.

Waves of chemical activity influence fruitfly embryo development

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Images of the fruitfly embryo showing waves of cell differentiation. Credit: Stefano DiTalia

Scientists have discovered that traveling “waves” of chemicals can quickly transfer information from cell to cell in a synchronized way. These synchronized waves of protein activity are emerging as an important form of cell communication that regulates embryonic development. These waves are also involved in adult cell functions, such as heart contractions and in the transmission of signals in the brain.

However, very few scientists have been able to image, quantify and mathematically describe these waves. In a recent paper, Duke University assistant professor Stefano Di Talia, Ph.D. student Victoria Deneke, and colleagues did just that. They show that waves of protein activity that spread across the fruit fly embryo synchronize its rapid cellular divisions. When they introduced a physical barrier halfway along the embryo, the wave of division did not go through the barrier, demonstrating that the activity is dependent on a signal that diffuses through the embryo. The behavior of stem cells must be coordinated across the whole tissue or organ for maintaining stability.

Their findings may hold the key to understanding how and when cells communicate during different stages of tissue development, and may be important to help understand how cells behave during tissue repair and regrowth. This finding may even lead to a better future understanding of why cancerous cells are not stable and multiply so rapidly. The paper was published in Developmental Cell on August 22nd, 2016. Read it here: http://dx.doi.org/10.1016/j.devcel.2016.07.023

Faculty position in Regenerative Medicine and Biology

Join our growing group of researchers!

The Regeneration Next Initiative (RNI) is partnering with basic and clinical departments throughout Duke University School of Medicine to hire a tenure-track faculty member at the Assistant Professor level. An appointment at the Associate or Full Professor level is possible for exceptional senior applicants. We invite applications from accomplished scientists with expertise and innovative approaches to developmental and cell biology, quantitative biology, imaging, stem cell biology, mechanisms of tissue regeneration, or tissue engineering.

A primary appointment will be made in a department most relevant to the candidate’s research, with possibilities for joint appointments. Candidates must have a Ph.D., M.D., or equivalent degree and will have a strong record of creativity and productivity in a field broadly related to tissue regeneration. Qualified minority candidates are especially encouraged to apply.

Applicants should submit a cover letter, curriculum vitae, a 3-page total summary of accomplishments and research plans, a teaching statement, and at least 3 letters of recommendation by November 15, 2016 to https://academicjobsonline.org/ajo/jobs/7911.

Questions may be directed to: Ken Poss, Director, RNI (regeneration@duke.edu).

Applications must be submitted online; emailed applications will not be accepted.

Gersbach lab breakthrough: directly reprogramming cells into neurons

IImage of Charles Gersbachmagine if scientists and doctors could make new neurons from your own skin cells and implant them in the brain to treat conditions such as Parkinson’s disease. Dr. Charles Gersbach and his colleagues have discovered a step towards such a treatment by directly turning connective tissue cells into neurons. In a recent paper in the journal Cell Stem Cell, Dr. Gersbach, his student Josh Black, and colleagues describe a gene editing method that activates three key genes in a mouse connective tissue cell – the three genes that produce the transcription factors to reprogram these cells into neuronal cells. The breakthrough comes from modifying a well-established gene editing method called CRISPR to directly edit the genes in the cell itself, rather than to introduce a virus with the copies of these genes as is traditionally done with other reprogramming methods.

Their results show that the neuronal cells converted using this method have a more complete and longer-lasting conversion compared to traditional methods. The new technique provides a way to reprogram cells without having to insert genes into the genome. It could pave the way to model neurological disorders and perhaps in the future, to develop personalized therapies using a patient’s own reprogrammed cells. For a detailed write-up of the paper’s implications, see: https://bme.duke.edu/about/news/60925

Mouse neuronal cells generated using the gene editing method developed in the Gersbach Lab.

 

Congratulations, 2017 Duke RNI Fellows!

Regeneration Next is pleased to announce the inaugural class of RNI Fellows. This group of outstanding scientists was chosen from a competitive pool of applicants. As the inaugural cohort, this group of scholars will play a key role in shaping and growing the regeneration science community at Duke. Congratulations to our four new RNI Fellows! Please stop by our annual retreat to hear more about their work and to congratulate them in person.

sehwon_koh Sehwon Koh, Ph.D.
Sehwon is a postdoctoral fellow in the Department of Cell Biology at Duke’s School of Medicine. In Dr. Cagla Eroglu’s lab, Sehwon has shown that cells isolated from human umbilical cord tissue can produce molecules that help retinal neurons from the eyes of rats grow, connect and survive. This finding may have therapeutic potential for the treatment of degenerative eye diseases in humans. Read more about Sehwon’s work here.

 

pilazLouis-Jan “LJ” Pilaz, Ph.D.
LJ completed his PhD thesis in France, working on cell cycle regulation in the neural stem cells of the developing mouse cortex. As he started working on these beautiful cells, he quickly fell in love with them. Neural stem cells are so fascinating and hold so many mysteries, he had to keep studying them. He now works in Dr. Debby Silver’s lab, in Duke’s Molecular Genetics and Microbiology department. Here, he uses live imaging to watch neural stem cells do what they do so well: produce neurons. LJ and his colleagues discovered that a delay in neural stem cells mitosis alters the fate of the cells they produce. This finding may explain why various mutations of mitosis genes lead to microcephaly, a disease where impaired neuron production leads to a smaller brain. With the support of the Regeneration Next fellowship, he hopes to now discover the underlying mechanisms linking longer neural stem cell mitosis and altered cell fate. Read more about LJ’s work here.

J_SawyerJessica Sawyer, Ph.D.
Jessica’s passion for basic research comes from a desire to understand how normal developmental and homeostatic programs are co-opted during disease. As a postdoctoral fellow in Dr. Don Fox‘s laboratory, she has developed a novel Drosophila intestinal tissue model at the boundary between the midgut (small intestine) and the hindgut (large intestine). As a RNI fellow, she plans to further dissect the molecular mechanisms of how cells residing at organ-organ boundaries maintain boundary integrity during development, contribute to tissue repair, and prevent tumorigenesis after tissue injury. Read more about Jessica’s work here.

 

Schweller_RM_0Ryan Schweller, Ph.D.
Ryan is a postdoctoral fellow in Duke’s Biomedical Engineering department, where he works in Dr. Jennifer West’s lab. Ryan’s current research focuses on understanding how cells remodel their extracellular matrix in three dimensions and using this information to create new materials capable of inducing desired cellular phenotypes. With the support of the Regeneration Next Fellowship, he will focus on the creation of new biomaterials which can enhance microvascularization and work towards wound healing applications and the treatment of ischemias such as peripheral artery disease. Read more about Ryan’s work here.

Save the date: Duke Pinnell Symposium

Duke’s Pinnell Center for Investigative Dermatology is hosting a symposium on Oct 28th that features several regenerative medicine experts. Among the speakers: Dr. Niroshana Anandasadapathy is an expert in dendritic cell vaccination, tumor immunology, and skin immunity. Dr. Todd Ridky’s research focuses on cutaneous genetically modified 3D cancer models, regeneration, and tumor invasion. Dr. Dennis Roop is a leader of skin stem cell biology and regenerative medicine and the leader of the Gates Stem Cell Center in Colorado. More information>

As Stem Cell research advances, scientists urge caution

The International Society of Stem Cell Research, or ISSCR, is the nation’s leading nonprofit organization of stem cell researchers. ISSCR recently launched a website to inform the public about the enormous promise of stem cell research. Stem cells have proven to be safe and effective to treat certain diseases such as leukemia and for certain types of tissue grafts. However, there has recently been a proliferation of clinics, many offering stem cell treatments that have not been tested or proven to work. Not only are they ineffective, these unregulated treatments can have dangerous side effects. Regeneration Next supports responsible and ethical stem cell research to ensure their great potential is utilized without causing harm to patients.

How can you tell which treatments work and which to avoid? Read ISSCR’s article, “Nine things to know about Stem Cells“, to learn more.  For further reading, this New York Times article takes a deeper look into the challenges facing scientists and researchers in communicating the dangers of unregulated stem cell research.

Regeneration Next Annual Retreat – call for Abstracts

The Regeneration Next first Annual Retreat will take place on October 4th, 2016 at the Trent Semans Center at Duke University, Durham.
Dr. Tom Rando of Stanford has been confirmed as our keynote speaker. A draft agenda and other details will be posted in the upcoming weeks.

We are pleased to invite abstract submissions from Duke trainees and early-career faculty for our first retreat. The full call for abstracts and submission instructions can be found here.

FAQ: Postdoctoral Fellowship Applications (due July 15!)

Regeneration Next postdoctoral fellowship applications are due July 15th! The full callout is here.

To help you in preparation of your application, we have compiled a list of questions received as of July 5 July 7, 2016. Additional questions should be sent to Dr. Sharlini Sankaran and will be posted on this Q&A page.

Q:  Who is eligible for this fellowship?
A:  Any postdoctoral associates/ postdoctoral researchers/ postdoctoral scholars who are currently performing research related to tissue regeneration in Duke University laboratories, except those who are already in the labs of one of the Regeneration Next Co-directors (Poss, Sherwood, Bursac, Alman labs). Postdoctoral researchers who are not currently at Duke are not eligible for this round of fellowships.

Q:  How much is the stipend?
A:  The stipend is $55,000 to be spent over two years.

Q:  What will the stipend cover?
A:  The stipend will partially cover stipend, benefits, and research expenses. This stipend will not cover travel.

Q:  My mentor is currently not affiliated with Regeneration Next, can I apply?
A:  Yes! Indeed, we encourage applications from researchers from any mentor interested in regeneration-related research at Duke. Remember that the mentor must provide one of the three required letters of reference.

Q:  Must the citations/references be included in the 5-page limit, or can they be separate?
A:  The citations/references can be separate and in addition to the 5-page limit for the research proposal.

Q:  What should be the subject line in the email for letters of reference?
A:  The subject line should include the applicant name, the words “RNI Fellows Application”, and be clear that it is a letter of reference. E.g: RNI Fellows Application Reference Letter – Sharlini Sankaran, Ph.D.

Q: I am an incoming postdoc, and have already accepted employment in a Duke University lab beginning Fall 2016. Am I eligible to apply?
A: Yes, as long as your Duke mentor provides one of the three Letters of Reference.

Q: What font size and spacing should I use?
A: We did not specify a format to use; however it is always a good idea to submit an application that is readable by the reviewers. By “readable”, we suggest at least 10pt Arial or similar font, at least 1.15 lines spacing, and at least 0.5″ margins.

We look forward to receiving and reviewing your applications!

Ken Poss receives American Heart Association Award

Ken Poss, Ph.D.

Ken Poss, Ph.D.

Kenneth Poss, PhD, James B. Duke Professor of Cell Biology, medicine and biology and Director of the Duke Regeneration Next Initiative, has received a $1 million merit award from the American Heart Association. The Merit Awards support scientists who propose novel approaches to major research challenges in cardiovascular disease and stroke that have the potential to produce an unusually high impact. Dr. Poss will study how cardiac cells regenerate.

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