Category Archives: Wisconsin Stem Cells

Postdoctoral Fellow

The Bo Liu laboratory: Vascular Biology Research Laboratory

An NIH funded postdoctoral position is available immediately in a Vascular Biology Research Laboratory of University of Wisconsin, Madison to investigate pathophysiology of a vascular disease called abdominal aortic aneurysm. The incumbent is expected to use mouse models of aneurysm as well as 2D- and 3-D cell cultures to study how extracellular matrix proteins influence vascular inflammation. Ph.D. or M.D./Ph.D. in cell biology, physiology, or related biomedical fields are required. Experiences in transgenic mice, mouse survival surgery, and immunohistology are desired.

Please send curriculum vitae to:Bo Liu, Ph.D. at liub @surgery.wisc.edu

Postdoctoral Fellow

The David Gamm laboratory at the Waisman Center, University of Wisconsin-Madison is seeking a postdoctoral fellow to work on funded projects involving derivation of retinal cell types from human embryonic stem (ES) and induced pluripotent stem (iPS) cells for use as models of human retinal development and disease. For more information about specific research interests and current projects, see http://stemcells.wisc.edu/node/158

A PhD background in genetics, molecular biology or cell biology is preferred. Additional experience in vision sciences, physiology, developmental biology, and/or stem cell biology would be advantageous, although not required.

Interested candidates should e-mail a cover letter and a copy of their current CV to: Dr. David Gamm at dgamm@wisc.edu Lynda Wright at wright@waisman.wisc.edu

Research Associate (Postdoctoral)

Department of Surgery and McPherson Eye Research Institute

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Career Opportunities | Stem Cell and Regenerative Medicine ...

Sept. 23, 2014

A multidisciplinary team at the University of Wisconsin-Madison and the Morgridge Institute for Research is creating a faster, more affordable way to screen for neural toxins, helping flag chemicals that may harm human development.

The National Institutes of Health (NIH) announced today that the UW-Madison and Morgridge team is among 11 universities receiving support to continue the promising work as part of the Tissue Chip for Drug Screening program. The team will receive approximately $7 million over the three-year project.

Inside wells about a fifth the size of a dime, the team grew neural tissues from a combination of cell types that represent the main components of a developing brain. This image shows the entire structure formed in the well, with nuclei in blue, neurons in green and glial cells in red.

Confocal microscopy image: Michael Schwartz

The next phase of the NIH program aims to improve ways of predicting drug safety and effectiveness. Researchers will collaborate to refine existing 3-D human tissue chips and combine them into an integrated system that can mimic the complex functions of the human body.

"We aim to get more treatments to more patients more efficiently," says Christopher P. Austin, director of the NIH's National Center for Advancing Translational Sciences (NCATS). "That is exactly why we are supporting the development of human tissue chip technology, which could be revolutionary in providing a faster, more cost-effective way of predicting the failure or success of drugs prior to investing in human clinical trials."

The UW-Madison team has succeeded in getting human pluripotent stem cell-derived neural progenitor cells to grow in a 3-D hydrogel environment. From there, the cells differentiate, self-organize, and mature into complex neural tissues. About one-fifth the circumference of a dime, the microenvironments assemble into three-dimensional tissue models that mimic the structure and function of the developing brain.

In tandem with the biological work, the team is testing a machine-learning algorithm that can predict toxic responses to compounds added to these constructed environments. Early results on a 2-D system with 45 known toxins or control compounds produced 100 percent accuracy.

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UW-Madison team developing tissue chip to screen neurological toxins

University of Wisconsin-Madison chemistry professor Laura Kiessling and her lab published new findings regarding stem cell differentiation Monday, according to a university press release.

Kiesslings study, which was published in the Proceedings of the National Academy of Sciences, describes how the qualities of surfaces on which pluripotent stem cells are grown affect the fate of these cells.

Kiesslings lab conducted research by placing pluripotent stem cells on brain tissue-like surfaces and observing their differentiation. Among other conclusions, the researchers found surface quality alone could influence cells to become neurons, according to the release.

Pluripotent stem cells are those that have yet to be assigned a specific role, thus they have potential to develop into any adult cell in the body.

The lab, directed by Kiessling and led by UW-Madison chemistry graduate student Samira Musah, created three types of gels to mimic liver, muscle and brain tissue.

The researchers found the cells on stiffer surfaces maintained a stem cell state, whereas those moved to a softer surface started to become neurons.

It was stunning to me that the surface had such a profound effect, Kiessling said in the release.

According to the release, the researchers believe the brain tissue-like surface quality affects the yes-associated protein 1, a potent oncogene, inside the cell.

YAP can be found either in the cytoplasm or nucleus of a cell. When located in the nucleus, YAP regulates gene expression.

Kiesslings study reports YAP is excluded from the nucleus when on soft surfaces, which helps direct the stem cells into brain cell development.

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Kiessling lab finds impact of surface conditions on stem cell growth

MILWAUKEE, Aug. 28, 2014 /PRNewswire-USNewswire/ -- BloodCenter of Wisconsin's Diagnostic Laboratories today announced the availability of an innovative Erythroid Chimerism test to monitor erythroid lineage chimerism in patients with sickle cell disease (SCD) following allogeneic bone marrow transplantation. This allows the physician to directly gauge the success of the transplant in these patients and provides physicians with actionable information to guide patient care.

Sickle cell disease is a common and severe autosomal recessive disorder caused by a mutation in the hemoglobin gene. SCD affects approximately 100,000 people in the United States, one in every 300-500 African Americans. In SCD patients with severe clinical symptoms, allogeneic bone marrow transplantation can be used to replace the blood cell producing capacity, potentially curing them of the disease.1

In patients with SCD, several studies have demonstrated that standard chimerism assays do not always reflect chimerism in the erythroid lineage.2,3 Since red cells do not contain DNA, chimerism of the erythroid compartment can be monitored using HbA and HbS transcripts produced from the hemoglobin gene and expressed in red cell progenitors.

"Efficient and accurate monitoring for post-transplant therapy is critical in order to properly manage patient care," said Daniel Bellissimo, Ph.D., director of BloodCenter's Molecular Diagnostic Laboratory. "The addition of BloodCenter's Erythroid Chimerism test reflects its ongoing commitment to advancing patient care by providing physicians worldwide with leading-edge testing in the area of molecular testing."

BloodCenter's Diagnostic Laboratories help physicians provide clinical care to patients worldwide, fostering better understanding and treatment options for patients with difficult-to-diagnose diseases. In addition, the laboratories collaborate with other institutions and industry partners to bring new diagnostic testing and treatment options to patient care.

About BloodCenter of Wisconsin BloodCenter of Wisconsin is a not-for-profit organization that specializes in blood services, organ, tissue and marrow donation, diagnostic testing, medical services and leading-edge research. BloodCenter of Wisconsin is the only provider of blood to 56 hospitals in 29 Wisconsin counties as well as providing support to hospitals and patients across the country. BloodCenter of Wisconsin advances patient care by delivering life-saving solutions grounded in unparalleled medical and scientific expertise. For more information,visit http://www.bcw.edu.

References:

1) Bernaudin F., Socie G., Kuentz M., Chevret S., Duval M., Bertrand Y., et al. (2007) Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood 110: 27492756

2) Wu, Catherine, et al. Molecular assessment of erythroid lineage chimerism following nonmyeloablative allogeneic stem cell transplantation. Experimental Hematology (2003) 31: 924-933.

3) Andreanni, Marco et al. Quantitatively different red cell/ nucleated cell chimerism in patient with long-term, persistent hematopoietic mixed chimerism after bone marrow transplantation for thalassemia major or sickle cell disease. Haematologica (2011) 96:128-133.

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BloodCenter of Wisconsin Launches Erythroid Chimerism Test for Monitoring Transplanted Sickle Cell Disease Patients

What is regenerative medicine, and what role does it play in the field of medical research?

For centuries, medical research has sought to treat injuries and degenerative diseases that lead to organ failure and chronic health conditions. Many of these conditions are genetic, and have been a leading cause of pain, suffering, and even death for generations of Americans. From the time of the first blood transfusions in the eighteenth century, medical researchers have sought to replace diseased or damaged tissue through organ transplantation. Although some initially opposed the concept of organ transplantation on religious grounds, on the basis that it altered the human body as God had made it, nonetheless millions of lives have been saved by heart, lung, kidney and other organ transplant surgeries. The vast majority of Americans consider it commonplace and entirely moral to alleviate suffering by replacing diseased human tissue with healthy donor tissue.

Organ transplantation has been hampered by long waiting lists for donor organs and difficulties in overcoming the human bodys natural tendency to reject foreign tissue. As a result, researchers have developed mechanical and synthetic devices that can function as artificial organs and tissues. These advances were also criticized by a vocal minority on religious grounds, on the basis that the transplantation of artificial organs into patients diminished the dignity of the human body. However, once again the vast majority of Americans hailed breakthroughs like artificial hearts and insulin pumps for the countless lives that they saved and for the human suffering that they alleviated.

Unfortunately, artificial medical devices are not a complete substitute for the healthy organs that they are designed to replace. In addition, despite advances in nanotechnology, researchers are still struggling to artificially replace human biological functions that occur at a cellular level. Today the search continues for ways to completely cure damaged and diseased human organs and tissue through artificial replacements.

Meanwhile, beginning in the 1970s, significant progress was made in the field of recombinant DNA. Researchers used strands of human DNA inserted into bacteria to manufacture drugs, proteins and artificial hormones that exactly mimic their parallels in the human body. For example, for decades diabetics stayed alive by replacing the human insulin that their bodies no longer made with insulin harvested from slaughtered pigs. Scientists now insert strands of human DNA into bacteria in order to manufacture artificial insulin that is genetically identical to human insulin. The insulin must still be injected into the patient several times a day, so it is a poor second best to replacing the patients damaged pancreas. However, the genetically manufactured insulin is superior to the pig insulin. Cancer treating drugs, such as those that boost red blood cell production during chemotherapy, are also manufactured using recombinant DNA.

The field of regenerative medicine promises to become the endpoint of this long history of medical research. Regenerative medicine applies tissue engineering, stem cell therapy, medical devices and other techniques in order to repair damaged or diseased tissues and organs. Stem cell research allows us to understand the process of human biology at a cellular level, and is therefore one way that researchers hope to learn how to repair or replace human organs and tissues. New cells can be created either through the transformation of one type of specialized cell into another or through the growth of specialized cells out of undifferentiated stem cell lines. The creation of new human organs and tissues, if successful, would mean that seriously ill Americans could be treated with therapies that completely cure their conditions rather than merely treat their symptoms. It is likely that, as with other medical advances over the centuries, there will still be a minority of Americans who react to these advances out of fear or by making claims that medical researchers are playing God. However, just as was the case with blood transfusions, organ transplantation and recombinant DNA, the majority of Americans fully support these medical advances that have the potential to so greatly improve the quality of life for themselves and their loved ones.

What are stem cells?

Stem cells are unspecialized cells that can generate healthy new cells, tissues, and organs. They are the master cells of the human body that can transform themselves into more specialized cells, that in turn perform a specific bodily function such as making the heart beat or secreting a particular hormone. In a human embryo, stem cells form four or five days after fertilization of the egg, and they are the precursor of all of the other cell types that will later be necessary for human development. After birth, stem cells remain in some of our organs, continuing to create specialized cells to replace cells that are damaged or wear out.

A stem cell line is comprised of a group of stem cells that are isolated from either an early stage embryo called a blastocyst or from adult tissue. These stem cells are then placed into a growth culture in a petri dish and induced to self-replicate, generating a colony of cells that continually replaces itself. Researchers then begin the hard work of learning what factors cause the stem cells to transform into one type of cell versus another. Although a relatively new area of scientific inquiry, the study of stem cells has already greatly increased our understanding of human cell biology.

What is involved in stem cell research?

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Wisconsin Stem Cell Now Stem Cells in Wisconsin

Despite advancements in cancer treatment, breast cancer remains the most common cancer among Singapore women[1]. Thirty percent[2] of early breast cancer patients in the world experience relapse due to metastasis, or the spread of cancer cells to other organs in the body. Some patients also do not respond well to chemotherapy. The inability to forecast relapses or the effectiveness of chemotherapy has led to a pressing need to identify predictive markers, which doctors can use to tailor appropriate treatment for each breast cancer patient at an early stage.

In a study published recently in the Journal of Clinical Investigation, a top-tier journal for discoveries in basic and clinical biomedical research, the team of scientists jointly led by Dr Vinay Tergaonkar, Principal Investigator at IMCB and Dr Alan Prem Kumar, Principal Associate at CSI Singapore and Assistant Professor at the Department of Pharmacology, NUS Yong Loo Lin School of Medicine, uncovered a gene, DP103, which is activated in metastatic breast cancer. DP103 acts as a master regulator, which expresses two sets of unfavourable proteins - one leads to metastasis and the other causes patients to be unresponsive to chemotherapy. Consequently, doctors can predict the probability of metastasis by examining the levels of DP103 in breast cancer patients. The same gene could also be used to predict whether a patient would respond to chemotherapy.

"Doctors are unable to tell if a breast cancer patient will respond to chemotherapy until six months after the treatment has been prescribed. It is very worrisome as the ones who are not responsive to chemotherapy usually also suffer relapses due to metastasis. This DP103 gene that we found explains the link and will facilitate doctors in selecting suitable treatments for different cases of breast cancer," said Dr Tergaonkar.

In addition, the study revealed that reducing the levels of DP103 could contain the cancer, shrink the tumour and make patients more amenable to chemotherapy. All the findings in the study have been validated with samples of breast cancer patients from Singapore, Canada, China and the USA.

"DP103 is a novel biomarker that could help doctors select appropriate treatments for breast cancer patients at an early stage. It is also a therapeutic target which could be explored further to develop drugs that suppress breast cancer growth, as well as metastasis," said Dr Kumar, who first discovered DP103's oncogene potential to drive breast cancer metastasis. He is also the Principal Inventor to a patent application on this discovery and is currently looking into ways to regulate DP103 levels in a variety of cancer types at CSI Singapore.

[1] Top 10 cancers affecting Singapore women: http://bit.ly/VEg7F8 [2] Lancet 365:1687-1717, 2005 - Early Breast Cancer Trialists' Collaborative Group: Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence; 15-year survival: An overview of the randomised trials

Notes to Editor:

The research findings described in this media release can be found in the Journal of Clinical Investigation Journal, under the title, "DEAD-box Helicase DP103 Defines Metastatic Potential of Human Breast Cancers" by Eun Myoung Shin 1,2, Hui Sin Hay 1,2,3, Moon Hee Lee 4, Jen Nee Goh 1,3, Tuan Zea Tan 1, Yin Ping Sen 5, See Wee Lim 5, Einas M. Yousef 6, Hooi Tin Ong 7, Aye Aye Thike 8, Xiangjun Kong 9, Zhengsheng Wu 9, Earnest Mendoz 10, Wei Sun 10, Manuel Salto-Tellez 1,11,12, Chwee Teck Lim 10,13,14, Peter E. Lobie 1,3,15, Yoon Pin Lim 16, Celestial T. Yap 17,18, Qi Zeng 2,16, Gautam Sethi 1,3, Martin B. Lee 19, Patrick Tan 1,20,21, Boon Cher Goh 1,18,22, Lance D. Miller 23, Jean Paul Thiery 1,2,16,18, Tao Zhu 9, Louis Gaboury 6, Puay Hoon Tan 8, Kam Man Hui 7, George Wai-Cheong Yip 5, Shigeki Miyamoto 4, Alan Prem Kumar 1,3,18,24,25, Vinay Tergaonkar 2,16.

1 Cancer Science Institute of Singapore, National University of Singapore, Singapore 2 Institute of Molecular and Cellular Biology, A*Star, Singapore Departments of 3 Pharmacology, 5 Anatomy, 11 Pathology, 16 Biochemistry, and 17 Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 4 McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Wisconsin, USA 6 Institute for research in immunology and cancer (IRIC), University of Montreal, Quebec, Canada 7 Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore 8 Department of Pathology, Singapore General Hospital, Singapore 9 Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, P.R. China 10 Division of Bioengineering and Department of Mechanical Engineering, National University of Singapore, Singapore 12 Centre for Cancer Research and Cell Biology, Queen's University Belfast, United Kingdom 13 Mechanobiology Institute, National University of Singapore, Singapore 14 NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 15 Liggins Institute, University of Auckland, New Zealand 18 National University Cancer Institute, Singapore 19 Renal Center, National University Hospital, Singapore 20 Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 21 Genome Institute of Singapore, A*Star, Singapore 22 Department of Haematology-Oncology, National University Hospital, Singapore 23 Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA 24 School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Western Australia 25 Department of Biological Sciences, University of North Texas, Denton, Texas, USA.

Full text of the Journal of Clinical Investigation paper can be accessed online from: http://www.ncbi.nlm.nih.gov/pubmed/25083991

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Novel Gene Predicts Both Breast Cancer Relapse and Response to Chemotherapy

Aug. 15, 2014

A coordination-retraining device was awarded first-round funding from the universitys Discovery to Product program. One key step to commercialization will be to test the device with stroke patients with varying levels of disability.

Photo: Kreg Gruben

An exercise machine that helps stroke victims walk. An advanced technology for assessing the progress of prostate cancer. A faster process for making neural stem cells to investigate new treatments for injury and disease. A cheaper, more beautiful LED light bulb. A game to teach meditation.

These projects, and a dozen more, are beneficiaries of the first round of awards by the University of Wisconsin-Madisons Discovery to Product, or D2P, program, which began operating in March. The 17 grants announced this week will support innovations in many fields of research at the university, from food engineering and medicine to stem cell biology and biomedical engineering.

None have yet reached the company stage. All have proven technology. And all have the potential to advance quickly to the market, says John Biondi, director of D2P. Our goal is to achieve commercialization by June 2015, defined as reaching a licensing agreement or creating a startup company that has a high probability of getting funded.

A new technology to create large quantities of nerve cells is also being funded by D2P.

Photo: Jeff Miller

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Grants fund UW technology projects on the road to commercialization