P R O G R A M

Connecticut’s Stem Cell and Regenerative Medicine Symposium

StemConn.org | #StemConn2017 | @StemConn2017

April 27, 2017Omni New Haven Hotel at Yale

New Haven, Connecticut

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Dear StemCONN Participant,

Welcome to StemCONN 2017. We are thrilled to host our sixth StemCONN conference, in which we celebrate 12 years of achievement in stem cell and regenerative medicine research in Connecticut. StemCONN 2017 highlights cutting-edge research advancements, and provides a forum for discussion among scientists, and policy makers. This year, there is an emphasis on reports from and interactions with Connecticut bioscience industry partners to advance knowledge, stimulate new collaboration, and foster bioscience in the state and region.

It continues to be a very exciting time in stem cell research, as new discoveries in the laboratory lead to medical breakthroughs and clinical therapies never before imagined. Through careful basic research, we learn how stem cells function, and how to use them to treat human injury and degenerative disease. We have gained new appreciation of the importance of the body’s own stem cells in maintaining organ health and promoting tissue repair and regeneration. The world-class science that will be shared at StemCONN 2017 embraces these themes.

StemCONN 2017 marks the 12th anniversary of the ground-breaking legislation that has propelled Connecticut to the forefront of stem cell and regenerative medicine research. The state’s investment in bioscience initiatives continues to pay dividends for its citizens — supporting major research advances, making possible state-of-the-art medical and research facilities, and creating opportunies and jobs. StemCONN2017 demonstrates the success of bioscience as a vehicle for medical progress and economic growth, by emphasizing the power of academia-industry partnerships and faculty entrepreneurship through biotech startups as a means to effectively move science discovery towards clinical application.

Science education is an important part of StemCONN’s mission. We welcome scientific trainees, postdoctoral fellows and graduate students. Trainees will have a special opportunity to meet with our invited speakers; and one of them will be honored with the Milton B. Wallack Trainee Award for Excellence in Stem Cell and Regenerative Medicine Research. StemCONN 2017 also welcomes college students from throughout Connecticut, who are attending the conference through support from our educational sponsors.

We thank all of our conference sponsors for their generous financial support. Please look through the sponsor list for the names of these contributors, and during the breaks, please be sure to visit our Exhibitor Forum. Thanks also to my colleagues on the StemCONN 2017 organizing committee for their enduring commitment and contributions to planning this conference.

Have a great day — and remember the essence of science is asking questions and seeking answers — so ask a question at StemCONN today!

Valerie Horsley Ph.D.

Chair StemCONN 2017 Organizing Committee

L E T T E R 1

On behalf of the University of Connecticut, including UConn Health, I am pleased to welcome you to StemCONN2017. As a forum for innovation and collaborative breakthroughs, StemCONN furthers the mission of our University as it aims for new heights of research and discovery. The vitality of this event is a testament to the commitment in our state to the economic and public health benefits of bioscience research in its many variations.

The University of Connecticut is proud to be a major contributor to the state’s stem cell and regenerative medicine research efforts, advancing through initiatives like Bioscience Connecticut, which to date has resulted in 21 biotech startup companies housed at the UConn Health campus, and the construction of state-of-the-art facilities devoted to research and medicine. That commitment can also be seen in the University’s move to join the Advanced Regenerative Manufacturing Institute this year, to further its goals in defining the 21st century frontier of medicine, which currently include regenerating a human knee in the next six years, and an entire limb by 2030. These path-breaking projects in stem cell and regenerative medicine directly benefit students in Connecticut’s universities, medical and dental schools, who will go on to make discoveries and advancements that benefit the whole world.

The University of Connecticut is committed to this work, and to the partnerships with industry leaders, government agencies, and other world-class universities that make it possible. Across efforts like its Technology Incubator Program, which has generated nearly $100 million in grant funding and revenue, and its collaboration with Jackson Laboratories, the University of Connecticut places a high premium on the benefits of working with innovators and entrepreneurs in these diverse fields. With this approach, and building on the early successes already in hand, the University is helping chart a course for bioscience in Connecticut that will make the state an international center of advancement and industry in the exciting and critically important industries stemming from it.

Susan Herbst

President University of Connecticut

2 L E T T E R

Wesleyan University is delighted to be a sponsor of StemCONN2017. Stem cell research is eagerly pursued by many of our faculty and students, and I take special pride in noting the work of Professor Stephen Devoto, who will be speaking in the morning about muscle development in the model organism zebrafish.

StemCONN highlights how private and public research institutions can work together with government to pursue goals of profound importance. At Wesleyan, funding from the state of Connecticut remains crucial in supporting our productive and multifaceted stem cell research program involving multiple laboratories, graduate students, postdoctoral fellows, and undergraduates. The impact beyond campus is evident in the publications of our life sciences faculty and their outreach educating the public on stem cell therapies for diseases. And on campus, the stem cell research of our scholar-teachers quickly finds its way from the laboratory into the classroom.

StemCONN provides remarkable opportunities to enrich perspectives on stem cell research through exchange, dialogue and collaboration; and I encourage all involved to take full advantage!

Sincerely,

Michael S. Roth

President Wesleyan University

L E T T E R 3

Welcome to the sixth biannual StemCONN! Over the course of this conference, you will connect with colleagues from Yale, across the country, and around the world to relay scientific advancements, network, and meet entrepreneurs in our state.

Connecticut’s generous support of the biosciences and stem cell research attracts renowned investigators and helps us build cutting-edge facilities. Our community of scientists, policy makers, and bioscience industry partners advance the field and contribute to the fiscal health of the state. All your efforts bring in research funding, create new jobs, establish companies, and retain our highly skilled workforce.

I am proud that the Yale Stem Cell Center is a part of this rich and active community. By working together, you will deepen our understanding of stem cell biology and harness its potential to improve human health. On behalf of Yale University, thank you for participating in this important endeavor.

Sincerely,

Peter Salovey

President and Chris Argyris Professor of Psychology Yale University

4 U P D A T E

The State of Connecticut is an acknowledged leader in the field of stem cell and regenerative medicine research. The prestigious journal “Cell Stem Cell”, February 5, 2015 cited CT together with California as having developed one of the leading state supported stem cell programs in the nation. Considering the size of our state, this is an enormous achievement. It reflects the unique collaborative relationship which has been developed among Yale, University of Connecticut, Wesleyan and now Jackson Laboratory (JAX).

The genesis of the original partnership dates back to 2005. That is when CT lawmakers passed legislation which included 100 million dollars in state funding for stem cell research over a 10 year period. Today more than 150 scientists across the state work in stem cell research with a significant number of additional support staff. The original financial commitment has attracted an additional 615 million dollars of federal (NIH) and philanthropic funding. Eight companies have been created which are directly related to stem cell research, and a number of others have been formed which are indirectly associated. At this time, others are in formation – some of which are related to UConn’s Technology Incubation Program (TIP) and venture capital firms are being attracted to this work. We have, in addition, seen the creation in CT of more than 300 skilled jobs related to stem cell research.

We have also seen the publication of more than 1,000 scientific papers, 350 patent filings, 50 industrial licenses obtained, and 400 invention disclosures. UConn has created 4 stem cell lines and is one of less than 10 academic institutions to establish such lines. They have also become world leaders in iPSC technology. Yale has received FDA approval for a cell-based therapy to repair congenital heart defects. Other break-throughs in CT have occurred in the areas of Parkinson’s disease, macular degeneration, vascular repair, skin regeneration, neuromuscular repair, bone and cartilage repair, as well as in the area of cancer research and therapies, and work has been initiated in even additional areas.

This has also led to the recently announced “Precision Medicine” initiative which is a collaboration between Yale, UConn and JAX. The economic potential of this program for the state is enormous. It has also spawned the “Metabolic Research Alliance” which includes these three institutions as well as the Weizmann Institute in Israel. Currently there are more than 250 research projects being conducted in CT, ranging from basic research to translational research and clinical application with the prospects for commercialization of new therapies and significant new job growth. Globally, the stem cell market is expected to experience double digit growth. As a leader in stem cell and regenerative medicine research, Connecticut has established a solid foundation for the development of a new biotech industry through the nurturing of medical discoveries. We are now poised for additional medical breakthroughs while at the same time enhancing the economy of the state of CT.

Dr. Milton Wallack

Founder, Connecticut Stem Cell Coalition

Connecticut Stem Cell & Regenerative Medicine Update – April 2017

T R I B U T E 5

Milton B. Wallack Trainee Award for Excellence in Stem Cell Research

StemConn2017 is delighted to recognize excellence in research conducted by a predoctoral or postdoctoral trainee through a merit-based award that recognizes highly innovative and important stem cell research. The Milton B. Wallack Trainee Award for Excellence in Stem Cell Research is presented in honor of

Dr. Milton B. Wallack, a founder of the Connecticut Stem Cell Coalition, a longtime member of the Connecticut Stem Cell Research Advisory Committee, and a consultant to the Regenerative Medicine Research Fund Advisory Committee.

The naming of this award both acknowledges and honors Dr. Wallack for his passionate support for stem cell research in the state of Connecticut. Through his efforts to bring together diverse interests toward a common purpose, Connecticut passed the Stem Cell Investment Act in 2005 — an Act supported by our state legislators, our former Governor Jodi Rell, and the people of Connecticut and committing $100 million in stem cell research funding over ten years. Dr. Wallack then worked with others to create the Regenerative Medicine Research Fund under Governor Dannel Malloy, which continued funding for stem cell and regenerative medicine research. Thanks in large part to these initiatives, Connecticut is now one of the top contributors to stem cell research.

Success in this groundbreaking research support required countless hours to initiate the Connecticut Stem Cell Coalition with Paul Pescatello at CURE, lobbying and establishing meaningful relationships with members of the state legislature, including former State Senator Chris Murphy, forging long-lasting connections between investigators throughout the state, and working with Connecticut Innovations. Since passage of the bill, Dr. Wallack’s tireless efforts continue in maintaining relationships with people in the legislature, assuring that Connecticut stem cell funding continues through 2016-2019, helping to organize each biennial StemConn meeting, and attending all of our tri-institutional retreats. He served consecutive terms as a devoted and hardworking member of the Stem Cell Research Advisory Committee (now called the Regenerative Medicine Research Advisory Committee), written countless editorials to local newspapers and business publications in favor of federal and state stem cell funding, helped Yale and UConn with fundraising efforts, and has served as a member of the Connecticut Economic Development Committee.

Dr. Wallack promotes collaborative scientific research between universities in Connecticut and Israel, as well as raises funds to support these international collaborations.

Dr. Milton Wallack has served the Connecticut stem cell community with unflagging optimism, diligence, and hard work. Dr. Wallack truly lives a life devoted to making the world a better place. In addition to all that he has done for Connecticut’s stem cell endeavors, he has contributed significantly to the Jewish community, juvenile diabetes care and research, and educational efforts throughout the state and the country. His leadership is worthy not only of honor but also emulation.

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8 S C H E D U L E

Symposium Breakfast

7:30 – 8:30 Registration & Continental Breakfast

Mezzanine & Pre Assembly Area

7:45 – 8:15 Symposium Breakfast Lecture*

College A/B * Pre-registration required

Ricardo Dolmetsch, Ph.D.Global Head of Neuroscience at the Novartis Institutes for BioMedical Research

Strategies for Treating Neurodegeneration

Symposium

8:30 – 8:45 Welcome / Connecticut Stem Cell Update Valerie Horsley, Ph.D. (Organizing Chair)

Maxine F. Singer Assoc. Professor of Molecular, Cellular & Developmental Biology Yale University Molecular, Cellular and Developmental Biology

Grand Ballroom A/B

8:50 – 9:10 Haifan Lin, Ph.D.Eugene Higgins Professor of Cell Biology, Genetics, and Obstetrics, Gynecology and Reproductive Sciences; Director, Yale Stem Cell Center, Yale University.

Uniting the Genome: A Novel Function of piRNAs in the Germline

9:15 – 9:35 Christine Finck M.D.Associate Professor of Pediatrics and Surgery, University of Connecticut; Surgeon in Chief, Connecticut Children’s Medical Center.

iPSC Differentiation to Alveolar-like Cells

9:40 – 10:25 Commercialization and Translation Session

9:40 Kyle Jensen, Ph.D. Associate Dean and Director of Entrepreneurship, Yale School of Management

9:55 Mostafa Analoui, Ph.D. Executive Director of Venture Development and Professor in Residence in the Department of Biomedical Engineering, University of Connecticut

10:10 Q&A

10:30 – 11:30 Posters and Exhibitor Forum, Break

Grand Ballroom C&D

11:35 – 11:55 Stephen Devoto, Ph.D.Professor of Biology, Neuroscience and Behavior, Wesleyan University

Grand Ballroom A/B

A Protection Racket: Tbx6 and the Establishment of Muscle Stem Cells in the Zebrafish Embryo

> continued

S C H E D U L E 9

Symposium (continued)

12:00 – 12:30 Molly Shoichet, Ph.D. Tier 1 Canada Research Chair in Tissue Engineering, University of Toronto

Can We Really Regenerate the Brain?

12:35 – 1:35 Lunch & Speaker-Trainee Groups* Sponsored by Thermo Fisher Scientific

George A, George B, Church, and Temple Rooms.* Pre-registration required. Check your name tag for Room Assignment.

Russell Jarres (Thermo Fisher Scientific)

Kristen Brennand, Ph.D. (Mount Sinai School of Medicine)

Molly Shoichet, Ph.D. (University of Toronto)

Hans-Willem Snoeck, M.D., Ph.D. (Columbia University)

Box lunches are available in the Mezzanine & Pre-Assembly Area. Take a boxed lunch en-route to your Speaker-Trainee Sessions.

1:40 – 2:10 Hans-Willem Snoeck, M.D., Ph.D.Professor of Medicine (Microbiology & Immunology), Columbia University

Grand Ballroom A/B

Modeling Human Lung Development and Disease Using Pluripotent Stem Cells

2:15 – 2:45 David T. Kuninger, Ph.D.Associate Director and Group Leader, Thermo Fisher Scientific

Evolving Your Media System for Modern Stem Cell Applications

2:50 – 3:10 Bill Skarnes, Ph.D.Director of Cellular Engineering, The Jackson Laboratory for Genomic Medicine

Genome Editing Approaches to Study Human Gene Function in a Model Cell

3:15 – 4:15 Posters and Exhibitor Forum, Break

Grand Ballroom C&D

4:20 – 4:40 Milton B. Wallack Trainee Award for Excellence in Stem Cell & Regenerative Medicine Research

Grand Ballroom A/B

Awardee announced and scientific presentation by awardee.

4:45– 5:15 Kristen Brennand, Ph.D.Associate Professor of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai

Modelling Predisposition to Schizophrenia Using Stem Cells

5:15 – 5:30 Closing Remarks Thermo Fischer Scientific Prize Drawing

Ricardo Dolmetsch, Ph.D.

Global Head of Neuroscience at the Novartis Institutes for BioMedical Research

Strategies for Treating Neurodegeneration

Dr. Ricardo Dolmetsch is Global Head of Neuro-science at the Novartis Institutes for BioMedical Research. His group is responsible for developing medicines to treat neuropsychiatric, neurodevel-opmental and neurodegenerative diseases. The group is focused on targets and mechanisms that have been validated in humans either by human genetic studies or by astute clinical observations. The department is a world leader in

developing preclinical models of disease using human induced pluripotent stem cells and has also developed novel methods for studying the function of circuits in the brain.

Ricardo joined Novartis from Stanford University where he was a Professor in the school of medicine. He was also a Senior Director at the Allen Institute for Brain Science. His group studied the molecular basis of autism and other neurodevelopmental disorders and was one of the pioneers in using induced pluripotent stem cells to model disease. His laboratory also played an important role in elucidating the molecular basis of calcium signaling in the developing nervous and immune systems.

Ricardo received his undergraduate degree from Brown University, his graduate degree from Stanford University and was a postdoctoral fellow at Harvard University. He continues to be an adjunct professor at Stanford Medical School.

1 0 A B S T R A C T / B I O G R A P H Y

Haifan Lin, Ph.D.

Eugene Higgins Professor of Cell Biology, Genetics, and Obstetrics, Gynecology and Reproductive Sciences;

Director, Yale Stem Cell Center, Yale University.

Uniting the Genome: A Novel Function of piRNAs in the Germline

The eukaryotic genome has vast intergenic regions containing transposons, pseudogenes, repetitive sequences, and noncoding genes that produce numerous long non-coding RNAs (lncRNAs) and PIWI-interacting RNAs (piRNAs). Yet the functions of the intergenic regions remain largely unknown. In mammals, a unique set of piRNAs, pachytene piRNAs, are abundantly expressed in the germline in late spermatocytes and early spermatids. Recently, we showed that piRNAs derived from transposons and pseudogenes mediate the degradation of a large number of mRNAs and lncRNAs in mouse late spermatocytes. In particular, they have a large impact on the lncRNA transcriptome, as a quarter of lncRNA expressed in late spermatocytes are upregulated in mice deficient in piRNA pathway. Furthermore, our genomic and in vivo functional analyses revealed that retrotransposon sequences are frequently found in the 3’ UTR of mRNAs that are targeted by piRNAs for degradation. Similarly, the degradation of spermatogenic cell-specific lncRNAs by piRNAs is mediated by retrotrans-poson sequences. Moreover, we have shown that pseudogenes regulate mRNA stability via the piRNA pathway. The degradation of mRNAs and lncRNAs by piRNAs requires MIWI and, at least in part, depends on its slicer activity. Together, these findings reveal a highly complex and global RNA regulatory network through which transposons and pseudogenes regulate target mRNA and lncRNA stability via the piRNA pathway to promote meiosis-spermiogenesis transition. This represents a novel paradigm of gene regulation.

Eugene Higgins Professor of Cell Biology and founding Director of Yale Stem Cell Center, Professor of Genetics and of Obstetrics, Gynecology, and Reproductive Sciences. Dr. Lin’s work is focused on the self-renewing mechanism of stem cells, using Drosophila germline stem cells, mouse germline, embryonic, and neural stem cells, as well as Hydra and planarian stem cells as models. He also studies germline development

and stem cell-related cancers. Dr. Lin received his BS degree from Fudan University (1982), and his Ph.D. degree from Cornell University (1990), and his postdoctoral training at the Carnegie Institution for Science. He joined the faculty of Duke University Medical School in 1994, where he rose to the rank of Full Professor. He founded and directed the Duke Stem Cell Research Program (2005-2006), and moved to Yale in 2006 to establish the Yale Stem Cell Center. In 2014, He became the Founding Dean (Adjunct) of School of Life Science and Technology at ShanghaiTech University. Dr. Lin has made key contributions to the demonstration of stem cell asymmetric division, and the proof of the stem cell niche theory. He discovered the Argonuate/Piwi gene family and their essential function in stem cell self-renewal and germline development. He is also a discoverer of PIWI-interacting RNAs (piRNAs), a discovery hailed by the Science magazine as one of the ten Scientific Breakthroughs in 2006. Recently, he proposed and demonstrated the crucial roles of the Piwi-piRNA pathway in epigenetic programming and in post-transcriptional regulation of mRNA and lncRNA. Dr. Lin has played many leadership roles in the ISSCR, the scientific community, and beyond. Dr. Lin received over 30 awards in his career, and is an Elected Fellow of the AAAS (2010-present).

A B S T R A C T / B I O G R A P H Y 1 1

1 2 A B S T R A C T / B I O G R A P H Y

Christine Finck M.D.

Associate Professor of Pediatrics and Surgery, University of Connecticut;

Surgeon in Chief, Connecticut Children’s Medical Center.

iPSC Differentiation to Alveolar-like Cells

Lung diseases are a major source of morbidity and mortality. In particular, premature infants have a significant risk of long term chronic lung disease. Many current treatment options alleviate symptoms but rarely address the underlying causes. The field of tissue engineering seeks to address these shortcomings. Induced pluripotent stem cells (iPSC) can be differentiated into all three germ layers including those found in the lungs and alveoli. Such cells and their progenitors can subsequently be used to repopulate decellularized lung scaffolding as a first step in patient specific disease modelling.

iPSCs were generated from human foreskin fibroblasts and differentiated toward an alveolar-like phenotype through endoderm and lung bud progenitor intermediaries. Cell phenotype was assessed throughout using flow cytometry, immunofluorescent staining and qRT-PCR for characteristic markers. Decellularized rat lung scaffolds were prepared by pressure controlled perfusion of the vasculature with SDS following which differentiated iPSCs were implanted and cultured.

At each stage of differentiation, marker expression was >90% including CXCR4 at definitive endoderm, FOXA2 at anterior foregut endoderm (AFE), TTF1 in lung bud progenitors and SPC at the alveolar stage. Cells taken at the AFE stage were able to repopulate a decellularized lung scaffold, integrating with and attenuating the extracellular matrix while maintaining phenotype.

Our differentiation protocol can produce a high purity of alveolar-like cells. Additionally these cells can be used to successfully repopulate lung scaffolds. Future work is focusing on seeding multiple cells types and functional assessments so as to produce a realistic premature lung disease model.

Christine Finck, MD, is the executive vice president and surgeon-in-chief at Connecticut Children’s Medical Center. In addition, Dr. Finck is the division head of pediatric surgery and is vice chair of the Department of Surgery at UConn School of Medicine. Dr. Finck completed her pediatric surgery fellowship at Arkansas Children’s Hospital and her surgical residency at SUNY Upstate Medical University at Syracuse.

She graduated with her Bachelor of Science from Boston University and earned her medical degree from SUNY Upstate Medical University at Syracuse. She is board certified in pediatric and general surgery. Through her own research, Dr. Finck is revolutionizing health outcomes of pediatric and neonatal diseases, most specifically spearheading efforts focused on identifying and treating those that affect the lungs, esophagus and brain. Her innovations in science were recognized by The Group on Women in Medicine and Science, who awarded Dr. Finck the Outstanding Clinical Scientist Woman Faculty Award. She was also recognized as a 2016 Hartford Business Journal Health Care Hero. Her dedication, leadership and expertise are paving the way to a better future for children across the region.

A B S T R A C T / B I O G R A P H Y 1 3

Commercialization & Translation Session

Kyle Jensen, Ph.D.

Associate Dean and Director of Entrepreneurship, Yale School of Management

Kyle Jensen is an entrepreneur, developer, and scientist. Before joining the Yale SOM faculty, he co-founded Agrivida, a venture-backed biotechnology company based in Boston; PriorSmart, a patent analytics provider (acquired by RPX, Nasdaq:RPXC); and Pit Rho, a leader in motorsport analytics. In addition to teaching, Kyle works

with numerous Yale start-ups as Associate Dean and Director of Entrepreneurship. His research interests include entrepreneurship, intellectual property, and innovation.

Mostafa Analoui, Ph.D.

Executive Director of Venture Development and Professor in Residence in the Department of Biomedical Engineering, University of Connecticut

Mostafa Analoui, Ph.D., is Executive Director of UCONN Ventures. Previously, he was Head of Healthcare and Life Sciences at Livingston Securities (New York, NY) with investment focus in private and public companies in biotech, medtech and healthcare services. Prior to that he was the Senior Director at Pfizer Global

Research and Development. Dr. Analoui is actively involved in investment, management and scientific/business development of nanotechnology, drug discovery/development, diagnostic imaging, and global strategies.

While at Pfizer, he was the Site Head for Global Clinical Technology in Groton and New London, a division focusing on emerging technologies for development and validation of biomarkers and diagnostics for drug development. Prior to joining Pfizer, Dr. Analoui was the Director of Oral and Maxillofacial Imaging Research, Associate Professor of Radiology at Indiana University, and Associate Professor of Biomedical Engineering and Electrical & Comp Engineering at Purdue University. He was also President and CEO of Therametric Technology Inc. He has received his Ph.D. from Purdue University, followed by Post-Doctoral Fellowship at IBM TJ Watson Research Center in NY.

In addition to industry leadership in biomedical and technology fields, he consults and lectures in US, Europe and Asia. He has also served on various scientific, regulatory, and business advisory committees and boards, including NIH, NSF, PhRMA, NASA, and OECD. Dr. Analoui has authored over 130 publications, including journal articles, book chapters and technical reports. Dr. Analoui is currently Adjust Professor at Brown University (Providence, RI), Northeastern University (Boston, MA) and University of Connecticut (Storrs, CT). He is also senior member of IEEE, SPIE, and RSNA.

He was Chairman of the Board of VirtualScopics (Nasdaq: VSCP) and currently serves as board member of Calando Pharmaceutical (Nasdaq: ARWR), BEACON (Biomedical Engineering Alliance and Consortium) and NanoBusiness Commercialization Association.

1 4 A B S T R A C T / B I O G R A P H Y

Stephen Devoto, Ph.D.

Professor of Biology, Neuroscience and Behavior, Wesleyan University

A Protection Racket: Tbx6 and the Establishment of Muscle Stem Cells in the Zebrafish Embryo

Tissue-specific stem cells are often specified very early during embryonic development, in an environment rich in growth factors that are triggering differentiation of neighboring cells. What protects those stem cell pre-cursors from differentiation? We use zebrafish to examine the molecular basis for the development of the dermomyotome, an early embryonic tissue which contains precursors to muscle-specific stem cells. We have shown that the Tbx6 transcription factor inhibits muscle differentiation and promotes dermomyotome formation. Using ChIP-seq we have identified the mesp-b transcription factor and the ripply1 co-factor as Tbx6 targets. Using loss of function, and transgenics with conditional overexpression, we show that Tbx6, mesp-b, and ripply1 are key components in a gene regulatory network that regulates the embryonic cell fate choice between muscle differentiation and muscle stem cell establishment.

The son of a Dutch immigrant and a Californian, Devoto was raised mostly in Northern California. He earned a Bachelor of Arts at Haverford College, and a Ph.D. in Neurobiology at The Rockefeller University, working with Colin Barnstable. He did a first postdoc at Duke University, working with Joe Nevins on the molecular biochemistry of the E2F transcription factor, and a second postdoc at the University of Oregon, working with Monte

Westerfield on the embryology and genetics of muscle fiber type development in zebrafish. Devoto established an independent research lab at Wesleyan University in 1997, where his research has been funded by a Basil O’Connor Starter Scholar Award from the March of Dimes, a Donaghue Investigator Award, and multiple NIH grants. His lab currently works on the molecular basis for embryonic muscle stem cell development, and the role of genes and environment in spine development. He serves as Chair of the Middletown Planning and Zoning Commission, and raises turkeys and pigs on a small hobby farm. He and his wife Joyce Powzyk have two children.

Molly Shoichet, Ph.D.

Canada Research Chair in Tissue Engineering, University of Toronto

Can We Really Regenerate the Brain?

Before the early 1990s, we were taught that the brain cannot regenerate. With the discovery of adult neural stem cells, we now know that the brain can regenerate – the questions are: how can we stimulate the endogenous stem cells and how can we transplant exogenous stem cells to achieve tissue and functional repair? Using rodent models of stroke, we are investigating both strategies. We transplanted both rodent neural stem cells and human induced pluripotent stem cell-derived neuroepithelial stem cells into rodent models of stroke and observed some tissue and functional repair. We designed a local strategy for the delivery of proteins that both stimulate neural stem cells and promote neurogenesis in similar models. These strategies highlight the opportunities and challenges of regenerative medicine strategies in the brain.

Professor Molly Shoichet holds the Tier 1 Canada Research Chair in Tissue Engineering at the University of Toronto. She has published over 530 papers, patents and abstracts and has given over 325 lectures worldwide. She currently leads a laboratory of 25 and has graduated 148 researchers. She founded two spin-off companies, is actively engaged in translational research and science outreach. Dr. Shoichet is the recipient of many

prestigious distinctions and the only person to be a Fellow of Canada’s 3 National Academies: Canadian Academy of Sciences of the Royal Society of Canada, Canadian Academy of Engineering, and Canadian Academy of Health Sciences. Dr. Shoichet was the L’Oreal-UNESCO For Women in Science Laureate for North America in 2015 and elected Foreign Member of the US National Academy of Engineering in 2016. She holds the Order of Ontario, Ontario’s highest honour and is a Fellow of the American Association for the Advancement of Science. In 2013, her contributions to Canada’s innovation agenda and the advancement of knowledge were recognized with the QEII Diamond Jubilee Award. In 2016, Dr. Shoichet became a Foreign Member of the United States National Academy of Engineering (NAE). In 2014, Dr. Shoichet was given the University of Toronto’s highest distinction, University Professor, a distinction held by less than 2% of the faculty. Dr. Shoichet received her BS from the Massachusetts Institute of Technology (1987) and her PhD from the University of Massachusetts, Amherst in Polymer Science and Engineering (1992).

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1 6 A B S T R A C T / B I O G R A P H Y

Russell Jarres

Technical Sales Specialist, Thermo Fisher Scientific

Students and post-docs interested in pursuing careers in industry should consider attending this lunch and speaker trainee session.

Russ graduated from the University of New Hampshire in 2001 with a BS in Microbiology and Genetics minor. His industry career began at Ionis Pharmaceuticals in a lead discovery group confirming antisense and siRNA hits in relevant cell models. Upon returning to the Boston area in 2005 he joined a spinoff of Vertex, Altus Pharmaceuticals, developing analytical chemistry methods and studying drug formulation

stability for clinical candidates. In 2006 Russ joined ALPCO Diagnostics, a small immunoassays distributor looking to develop their own products, to build their R&D, Manufacturing, QA, QC and Technical Support groups. After launching novel Mouse/Rat C-peptide and Proinsulin assays, he moved into commercial roles in Product Management and later Account Management. In 2014 he moved to Seahorse Biosciences to help build their Sales Development group before the company was acquired by Agilent Technologies. Most recently, Russ brought his research and drug development experience to the Life Sciences Group (Gibco/Invitrogen) at Thermo Fisher Scientific as a Technical Specialist for Stem Cells and Drug Discovery.

A B S T R A C T / B I O G R A P H Y 1 7

Hans-Willem Snoeck, M.D., Ph.D.

Professor of Medicine (Microbiology & Immunology), Columbia University

Modeling Human Lung Development and Disease Using Pluripotent Stem Cells

Columbia Center for Human Development, Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA

Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modeling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation. Infection in vitro with respiratory syncytial virus, which causes small airway obstruction and bronchiolitis in infants, led to swelling, detachment and shedding of infected cells into the organoid lumens, similar to what has been observed in human lungs. Introduction of mutation in HPS1, which causes an early-onset form of intractable pulmonary fibrosis, led to accumulation of extracellular matrix and mesenchymal cells, suggesting the potential use of this model to recapitulate fibrotic lung disease in vitro. LBOs therefore recapitulate lung development and may provide a useful tool to model lung disease.

Dr. Snoeck was trained as clinical hematologist, with a focus on bone marrow transplantation, and from that clinical interest developed a research program in hematopoietic stem cell biology, more specifically mechanisms regulating stem cell renewal and underlying quantitative genetic variation in the behavior of hematopoietic stem cells among inbred mouse strains. Expansion of this program into directed differentiation of ES

and iPS cells into thymic epithelial cells arose from the desire to attempt to alleviate post-bone marrow transplantation immune deficiency, caused, among others, by defective T cell reconstitution. In addition, through these studies into the development of anterior foregut endoderm from ES and iPS cells, the lab also focuses on the generation of lung tissue from pluripotent cells.

1 8 A B S T R A C T / B I O G R A P H Y

David T. Kuninger, Ph.D.

Associate Director and Group Leader, Thermo Fisher Scientific

Evolving Your Media System for Modern Stem Cell Applications

Culture systems for pluripotent stem cell (PSC) expansion enable generation of a nearly unlimited pool of cells for downstream differentiation, disease modeling, drug discovery, and therapeutic applications. While a number of PSC feeder-free medium systems exist, there are many challenges encountered by stem cell scientists across the PSC workflow in today’s applications. Here we sought to improve the robustness and versatility of traditional PSC culture medium systems identify and optimize critical medium components. Through assessment of over 65 different formulations, an optimum medium composition was identified which provides compatibility across the PSC workflow from somatic cell reprogramming, PSC expansion, downstream differentiation, as well as providing support in stressful applications such as gene editing. This system additionally provides versatility, allowing for every-other-day or weekend-free feed schedules and compatibility with a broad range of passaging reagents and matrices. Together this system provides a robust next-generation stem cell medium system for today’s challenging PSC workflow needs. For Research Use Only.

Dr. Kuninger leads research, development and commercialization of next generation culture systems for pluripotent stem cell culture, differentiation, neurobiology and non-hepatic primary cell biology at Thermo Fisher Scientific in the Cell Biology business based in Frederick MD. His teams support numerous portfolios and have launched over 15 new products spanning stem cell culture & cryopreservation, differentiation

(endo-, ecto- and meso-dermal lineages) and neurobiology, leading to more than 25M in revenue over the last 3 years. David is a seasoned scientist and manager, experienced in media formulation & optimization as well as with sophisticated experimental design and data modeling tools applied to cell imaging and functional analysis endpoints as well as 2D and 3D culture models. Expertise in GLP/GMP compliance, technical transfer and scale up, verification and validation processes. Prior to starting at Thermo Fisher Scientific (legacy Invitrogen) in 2007 as Staff Scientist, he joined Oregon Health Sciences University (OHSU) as a Postdoctoral Fellow investigating the actions of insulin-like growth factors (IGFs) in the lab of Dr. Peter Rotwein, subsequently joining the faculty in the Department of Biochemistry at OHSU as a Research Instructor. He completed is PhD in Biochemistry and Genetics University of Texas Medical Branch, Galveston, Texas in the laboratory of Dr. John Papaconstatinou and has a B.S. in Chemistry from the University of Oregon in Eugene OR.

A B S T R A C T / B I O G R A P H Y 1 9

Bill Skarnes, Ph.D.

Director of Cellular Engineering, The Jackson Laboratory for Genomic Medicine

Genome Editing Approaches to Study Human Gene Function in a Model Cell

Human pluripotent stem cells are an ideal model system to study basic cellular and developmental processes in a normal diploid cell. The advent of site-specific nucleases and improved conditions for human iPSC culture now permits efficient engineering of human stem cells. CRISPR-Cas9 technology, in particular, provides a facile tool for the generation of biallelic mutations, thus empowering functional studies of human genes in a model human cell. Our aim is to generate and distribute arrays of human iPS cell knockouts that will be coupled to focused phenotyping screens in cultured cells. As a reference cell line for genome editing, we identified several low passage, karyotypically normal iPS cell lines form the HipSci resource (www.hipsci.org) and isolated a feeder-independent subclone, KOLF2-C1, that is highly amenable to genetic manipulation. Importantly, the cells have the proper consent for public release of whole genome sequence, allowing us to display cell line-specific variants in our public, genome browser-based, CRISPR design tool. Further detailed characterization of KOLF-C1 cells is ongoing, including single cell transcriptomics and epigenetic profiling of differentiating cultures. With this platform, we are beginning to scale the production drug-inducible conditional alleles. Similar to the yeast KO collection, a genome-wide resource of human KO cells will greatly accelerate the functional annotation of the human genome.

Dr. Skarnes, who is on the faculty at the Jackson Laboratory in CTm received his BSc and MSc in Microbiology and Immunology from McGill University in Montreal, Canada. He performed his Ph.D. studies in Molecular and Medical Genetics at the University of Toronto, where he pioneered gene-trapping technology in mouse embryonic stem (ES) cells. Hi then did postdoctoral training in Edinburgh, UK, and became a laboratory

group leader at the BBSRC Centre for Genome Research in Edinburgh. He later moved on to a faculty position at University of California Berkeley, where he worked with mutant ES cells for gene-based, phenotype-driven screens in mice. During this time, he helped to initiate a public gene trap resource called the BayGenomics programme. From 2003 to 2016, he led the Mouse Developmental Genetics and ES Cell Mutagenesis teams at the Sanger Center in the UK that established a high-throughput pipeline for the production of many thousands of targeted gene mutations in mouse ES cells for EUCOMM (European Conditional Mouse Mutagenesis Program) and KOMP (Knockout Mouse Project). At Jax, he is using genome-editing technology to study gene function and to model disease in human ES cells.

2 0 A B S T R A C T / B I O G R A P H Y

Kristen Brennand, Ph.D.

Associate Professor of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai

Modelling Predisposition to Schizophrenia Using Stem Cells

Schizophrenia (SZ) is a debilitating neurological disorder for which the molecular mechanisms underlying the disease state remain unclear. To address this, we reprogrammed fibroblasts from SZ patients into human induced pluripotent stem cells (hiPSCs) and subsequently differentiated these disorder-specific hiPSCs into neural progenitor cells (NPCs) and neurons. Our hiPSC neural cells, from controls and patients with SZ, better resemble fetal rather than adult brain tissue, indicating that hiPSC-based models may be best suited for studies of disease predisposition. We have previously reported aberrant migration, increased oxidative stress, abnormal WNT signaling and elevated global protein synthesis in SZ hiPSC NPCs, together with diminished neuronal connectivity, decreased neurite number, and impaired synaptic morphology in SZ hiPSC neurons. We are now applying our hiPSC-based models to investigate the link between genotype, gene expression and in vitro phenotype in SZ, for both common variants and rare mutations associated with disease.

Kristen Brennand, PhD is an Associate Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai, in New York, New York. She trained in developmental and stem cell biology at Harvard University and in neurobiology during postdoctoral at the Salk Institute for Biological Studies. By combining expertise in stem cell biology and neurobiology, her laboratory is pioneering a new approach by which to study

schizophrenia. To investigate how neurons from patients with schizophrenia differ from those from healthy controls, they obtain skin samples from patients, which are then reprogrammed into induced pluripotent stem cells, and subsequently differentiated into precise subtypes of human neurons. This has allowed her group to begin to ask how and why neurons derived from schizophrenia patients differ from those derived from controls. The goal of their research is to not just understand the genetic mechanisms contributing to schizophrenia, but ultimately to develop a screening platform that we can use to identify new therapeutics for the treatment of this debilitating disorder. Dr. Brennand’s work is funded by the National Institutes of Health, the New York Stem Cell Foundation, the Brain Research Foundation and the Brain and Behavior Research Foundation.

Symposium Organizers

Valerie Horsley, Ph.D. (Organizing Chair) Maxine F. Singer Assoc. Professor of Molecular, Cellular & Developmental Biology Yale University Molecular, Cellular and Developmental Biology

Stormy Chamberlain, Ph.D. Department of Genetics and Genome Sciences, UConn Stem Cell Institute, University of Connecticut Health Center

Caroline Dealy, Ph.D. Department of Reconstructive Sciences, Department of Orthopaedic Surgery, Center for Regenerative Medicine and Skeletal Development, UConn Stem Cell Institute, University of Connecticut Health Center

Susan Froshauer, Ph.D. President and CEO, CURE – Connecticut United for Research Excellence

David Goldhamer, Ph.D. Department of Molecular and Cell Biology, UConn Stem Cell Institute, University of Connecticut

Shangqin Guo, Ph.D. Department of Cell Biology, Yale Stem Cell Center, Yale University

Diane Krause M.D., Ph.D. Department of Cell Biology, Department of Laboratory Medicine, Department of Pathology, Associate Director, Yale Stem Cell Center Yale University

Janice Naegele, Ph.D. Department of Biology, Department of Neuroscience and Behavior, Wesleyan University

Lawrence Rizzolo, Ph.D. Department of Surgery, Department of Ophthalmology and Visual Science, Yale Stem Cell Center, Yale University

Milton Wallack, D.D.S. Connecticut Stem Cell Research Coalition, Connecticut Regenerative Medicine, Research Advisory Committee

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