Stem Cells, Small Molecules and Therapeutics

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Stem Cells, Small Molecules and Therapeutics

Wednesday, November 14, 2012

The New York Academy of Sciences

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Stem cells are of increasing importance as a research tool and as a therapeutic option for degenerative diseases. Small molecules have the potential to impact stem cell research in numerous ways. First, stem cells can be used to generate otherwise rare cell types for high-throughput screening of small molecules. Second, small molecules can be used to induce differentiation of stem cells down specific lineages. Third, small molecules can be used to create scaffolding materials that regulate stem cell function and increase the facility of culturing stem cells. Finally, it may be possible to create small molecules that regulate the endogenous stem cells in humans as a therapeutic option. This symposium will explore the intersection of small molecules and stem cells.

*Reception to follow.

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Please note: Transmission of presentations via the webinar is subject to individual consent by the speakers. Therefore, we cannot guarantee that every speaker's presentation will be broadcast in full via the webinar. To access all speakers' presentations in full, we invite you to attend the live event in New York City where possible.

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Agenda

* Presentation times are subject to change.


November 14, 2012

6:00 PM

Welcome and Opening Remarks
Jennifer Henry, PhD, The New York Academy of Sciences
Brent R. Stockwell, PhD, Columbia University

6:15 PM

Controlling Cell Fate Decisions with Chemistry
Laura Kiessling, PhD, University of Wisconsin, Madison

7:00 PM

Stem Cells and Reprogramming: A New Approach for the Study of Neurodegenerative Disease
Kevin Eggan, PhD, Harvard University

7:45 PM

Mini Compound Libraries and the Development of Stem Cell Based Assays
Eric Chiao, PhD, Hoffman-La Roche Inc.

8:30 PM

Networking Reception

9:30 PM

Close

Speakers

Organizers

Eric Chiao, PhD

Hoffmann-La Roche Inc.

Dr. Eric Chiao received his PhD from Columbia University, where he used embryonic stem cells to create mouse models of human diseases. His post-doctoral studies at Stanford University focused on developing human embryonic stem cells as a model system for studying endoderm formation. Later at Stanford, he was appointed the founding Director of the Human Pluripotent Stem Cell facility. There he worked deriving and differentiating disease-specific human embryonic stem cell and iPS lines, and training other researchers techniques for manipulating human pluripotent stem cells. In 2010, Dr. Chiao joined Hoffmann-La Roche in Nutley, NJ, serving as the head of the Pluripotent Stem Cell lab in the Early Investigative Safety group. His lab currently focuses on developing new stem cell based screens for use in drug discovery.

Michael Soth, PhD

Hoffmann-La Roche Inc.

Michael (Mick) Soth joined Roche in Palo Alto, California as a medicinal chemist, after postdoctoral studies at the University of Pittsburgh and graduate work at the University of California, Irvine. He moved to Roche's Nutley site in 2009. At Roche he has led and contributed to multiple programs, mostly in the kinase field. He is currently leading a chemical biology group focused on epigenetic targets.

Brent R. Stockwell, PhD

Columbia University

Brent Stockwell is a tenured Associate Professor at Columbia University in the Department of Biological Sciences and the Department of Chemistry, and is an Early Career Scientist of the Howard Hughes Medical Institute. His research involves the discovery of small molecules that can be used to understand and treat cancer and neurodegeneration. He has received numerous awards, including a BWF Career Award at the Scientific Interface, and a Beckman Young Investigator Award. He has published 63 scientific papers, is an inventor on 10 issued US patents, has given 66 invited presentations around the world, and has received 34 research grants for over $10 million. He co-founded the biopharmaceutical companies CombinatoRx (now Zalicus) and Solaris Therapeutics. He is also the author of The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines.

Jennifer Henry, PhD

The New York Academy of Sciences

Speakers

Eric Chiao, PhD

Hoffmann-La Roche Inc.

Dr. Eric Chiao received his PhD from Columbia University, where he used embryonic stem cells to create mouse models of human diseases. His post-doctoral studies at Stanford University focused on developing human embryonic stem cells as a model system for studying endoderm formation. Later at Stanford, he was appointed the founding Director of the Human Pluripotent Stem Cell facility. There he worked deriving and differentiating disease-specific human embryonic stem cell and iPS lines, and training other researchers techniques for manipulating human pluripotent stem cells. In 2010, Dr. Chiao joined Hoffmann-La Roche in Nutley, NJ, serving as the head of the Pluripotent Stem Cell lab in the Early Investigative Safety group. His lab currently focuses on developing new stem cell based screens for use in drug discovery.

Kevin Eggan, PhD

Harvard University

Dr. Eggan completed his bachelor's degree in microbiology at the University of Illinois in 1996. A two-year Pre-Doctoral internship at Amgen at the National Institutes of Health in Bethesda solidified his desire to pursue a career in academic research. He enrolled at the graduate school of Massachusetts Institute of Technology in 1998 shortly after the cloning of Dolly the Sheep was reported in Scotland. During his PhD training, he actively pursued projects focused on cloning, stem cells and reprogramming after nuclear transfer under the guidance of genetics pioneer, Dr. Rudolf Jaenisch. He stayed in Dr. Jaenisch's lab after his graduation for one-year of PostDoc training in 2002. During that time, he conducted a collaborative study with Dr. Richard Axel, a Nobel Prize winner at the Howard Hughes Medical Institute. In 2003, he moved to Harvard University as a junior fellow and then became an assistant professor of Molecular & Cellular Biology at the Stem Cell Institute in 2005. In 2012, Dr. Eggan received tenure and is now a full professor with the Department of Stem Cell and Regenerative Biology.

As a young investigator in the burgeoning field of stem cell biology, Dr. Eggan has garnered international recognition for his seminal work and a number of high profile awards for his creativity and productivity, including the MacArthur Foundation "Genius Grant" in 2006. His current research focuses on applying the knowledge gained in stem cell biology to studying the mechanisms underlying amyotrophic lateral sclerosis (ALS) and discovering new therapeutic targets. He made a significant impact in the field by publishing two high profile papers in Cell, Stem Cell, and Science in 2008. One paper described the discovery that motor neurons derived from human embryonic stem cells are susceptible to the toxic effect of glial cells harboring an ALS mutation while the other shows that induced pluripotent stem (iPS) cells generated from adult skin cells of ALS patients can be differentiated into motor neurons. In 2009, he was selected as one of 50 Howard Hughes Medical Institute Early Career Scientists who will receive six years of dedicated support to conduct transformative research. He will use this support to advance the use of both human embryonic stem cells and iPS cells in the study of ALS study and the development of new treatments.

Laura Kiessling, PhD

University of Wisconsin, Madison

Laura L. Kiessling PhD was born in Milwaukee, WI. She received her BS in Chemistry from MIT and her PhD in Chemistry from Yale University. After carrying out postdoctoral training in Chemical Biology at the California Institute of Technology, she returned to Wisconsin to begin her independent career at the University of Wisconsin-Madison. She currently is a Steenbock Professor of Chemistry and the Laurens Anderson Professor of Biochemistry. She also serves as the Director of the Keck Center for Chemical Genomics and the Program Director for the Chemistry-Biology Interface Training Program. Her interdisciplinary research interests focus on elucidating and exploiting the mechanisms of cell surface recognition processes, especially those involving protein-glycan interactions. Another major interest of her group is multivalency and its role in recognition and signal transduction. Her research combines tools from organic synthesis, polymer chemistry, structural biology, and molecular and cell biology.

Kiessling's honors and awards include the Arthur C. Cope Scholar Award and the Garvan Award from the American Chemical Society, the Harrison-Howe Award, a Guggenheim Fellowship, and a MacArthur Foundation Fellowship. She is a Fellow of the American Academy of Arts and Sciences and a Member of the National Academy of Sciences. She serves on several editorial boards and is Editor-In-Chief of ACS Chemical Biology. More information on Dr. Kiessling and her research can be found at www.biochem.wisc.edu/faculty/kiessling/lab.

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The Chemical Biology Discussion Group is proudly supported by




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Abstracts

Controlling Cell Fate Decisions with Chemistry
Laura Kiessling, PhD, University of Wisconsin, Madison

Human pluripotent stem cells (human embryonic stem cells and induced pluripotent stem cells) have the ability to self-renew indefinitely and differentiate into all cell types. The repertoire of signals that direct their propagation or differentiation is limited. The undefined culture conditions used typically complicates determining the requisite signaling pathways that must be activated or suppressed. Our goal is to identify chemically defined conditions to control human pluripotent stem (hPS) cell self-renewal and differentiation. In physiological settings, the microenvironment of the niche transmits information through three types of components: soluble molecules, neighboring cells, and the collection of secreted proteins and glycans that is termed the extracellular matrix. In seeking conditions for hPS cell culture and differentiation, researchers have focused identifying soluble components that influence cell decisions. To complement this approach, we have been exploring how defined synthetic insoluble components can be used to deliver signals that direct cell decisions. To mine this molecular space, we devised arrays of chemically defined surfaces composed of self-assembled monolayers. From these arrays, we identified surfaces with surprising assets: They not only permit human pluripotent stem cells to differentiate to specific lineages but even instruct them to do so. Our findings highlight the dramatic effects of insoluble cues on stem cell pluripotency and differentiation.
 

Stem Cells and Reprogramming: A New Approach for the Study of Neurodegenerative Disease
Kevin Eggan, PhD, Harvard University

In my laboratory, we pursue two interlocking areas of investigation: the basic biology of stem cell programming and reprogramming, as well as the application of the resulting technologies to studies of the neuromuscular system and the diseases that affect it.
 
A fundamental understanding of how a cell's identity is determined during differentiation and how it can in turn be manipulated experimentally is a central goal of developmental biology, one with substantial ramifications for biomedicine. We study both the differentiation of embryonic stem cells into the neural lineage and the reprogramming of commonly available differentiated cell types, such as fibroblasts, into either pluripotent stem cells or cells of therapeutic interest, such as spinal motor neurons. To study differentiation and dedifferentiation, we employ a variety of approaches, including stem cell differentiation, nuclear transfer, and defined reprogramming strategies using known transcriptional regulators and novel small-molecule compounds.
 
A number of devastating diseases, including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), specifically affect the neuromuscular system. Little is known concerning the molecular pathology underlying these conditions, partly because it has been impossible to access significant quantities of the disease-affected cell, the spinal motor neuron. With recent advances in stem cell and reprogramming biology, we can now produce billions of spinal motor neurons with control and diseased genotypes. We use this new resource to design in vitro disease models for both mechanistic studies and for the discovery of novel small-molecule therapeutics.
 

Mini Compound Libraries and the Development of Stem Cell Based Assays
Eric Chiao, PhD, Hoffmann-La Roche Inc.

Dr. Chiao will be presenting recent work performed in his lab aimed at creating new human pluripotent stem cell based assays for use in drug discovery.
 

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