Program Updates

• Registration is Open

  NYSTEM 2012
  Registration is now open
  Abstracts are due by March 9
  Early registration closes April 12.

• Stem Cell Awareness Day

  October 5, 2011 marked "Stem Cell Awareness Day." The winning images for NYSTEM sponsored third annual stem cell image contest are featured in the NYSTEM 2012 calendar

• Two RFAs issued

  September 28, 2011 - The New York State Department of Health issued two Requests for Applications: Institutional Awards for Short Term Faculty Training and Collaborative Opportunities; and, Empire State Medical, Dental and Veterinary Student Stem Cell Research Training Program.

• Information on Oocyte Donation

Conversion of Skin Cells From Alzheimer's Patients Into Functional Neurons

New research from the lab of Dr. Asa Abeliovich, M.D., Ph.D., at Columbia University Medical Center, shows that skin cells from Alzheimer´s disease (AD) patients can be converted directly into functional neurons, the cells damaged and lost in the disease. Dr. Abeliovich and his coworkers initially tried to replicate research in mice using three transcription factors, but this didn´t work. However, when his team added additional transcription factors and used a modified growth medium, they succeeded in producing what they call human induced neuronal (hiN) cells. Once generated, the hiN cells functioned normally both in culture and in vivo when inserted into mice. They went on to generate hiN cells from patients with inherited and sporadic forms of AD, and showed that patient-derived hiN cells exhibit early signs of AD. Finally, they introduced into mutant hiN cells a normal copy of one gene that causes an inherited form of AD and found that it alleviated some of the defects. These cells are already providing insights into how AD develops, and with their ability to integrate normally, may prove useful for cell-based therapies. This work was supported in part by two research awards to Dr. Abeliovich (contracts #C024402 and #C024403).

Qiang L, Fujita R, Yamashita T, Angulo S, Rhinn H, Rhee D, Doege C, Chau L, Aubry L, Vanti WB, Moreno H, Abeliovich A. Directed Conversion of Alzheimer's Disease Patient Skin Fibroblasts into Functional Neurons. Cell. 2011 August 5; 143 (3): 359-371.

Modification of Fusion Protein Causes Blood Cancers

Lan Wang, Ph.D., an Empire State Stem Cell Fellow at Memorial Sloan-Kettering Cancer Center, just published new data in Science identifying the mechanism behind the uncontrolled cell proliferation leading to certain blood cancers. Dr. Wang and her mentor, Stephen Nimer, M.D., study the blood cancer acute myelogenous leukemia (AML). Their new research identifies the mechanism by which one of the most common mutations leading to AML can cause uncontrolled cell growth. This mutation fuses two genes, AML1 and ETO, together. AML1 is necessary for development of stem cells that produce blood and ETO acts to repress transcription. However, the fusion product of these two genes is a potent activator of proliferation specifically in these blood stem cells. Drs. Wang and Nimer now show that post-translational acetylation, adding an acetyl group to a specific amino acid in AML1-ETO, is the key to AML1-ETO´s newfound activity. Further, inhibition of this acetylation reduces the growth of cancer cells. This finding presents an attractive target for development of new therapeutics and may be applicable to other types of cancers besides AML as well. This project was supported in part by a NYSTEM Fellow to Faculty award to Dr. Wang (contract #C026720).

Wang L, Gural A, Sun XJ, Zhao X, Perna F, Huang G, Hatlen MA, Vu L, Liu F, Xu H, Asai T, Xu H, Deblasio T, Menendez S, Voza F, Jiang Y, Cole PA, Zhang J, Melnick A, Roeder RG, Nimer SD. The Leukemogenicity of AML1-ETO Is Dependent on Site-Specific Lysine Acetylation. Science. 2011 Aug 5; 333 (6043): 765-769.

NYSTEM Investigator Unfolds the Dynamics between Hair Follicle Stem Cells and the Niche Microenvironment

New research findings published in Cell from the lab of Elaine Fuchs, Ph.D., at the Rockefeller University provide more clues to determine the point where stem cells lose the self-renewing capacity and commit irreversibly toward a specific cell fate. Through gene expression analysis and tracing experiments to test the function of hair follicle cells at different differentiated stages, researchers at Fuchs´ lab show that early stem cell descendents can retain the stemness and return back to their niche when hair growth stops. On the other hand, the committed stem cell descendents can transmit inhibitory signals back to the stem cells and instruct them to a dormant state. Such negative feedback loops can provide the necessary signals to regulate stem cells in the niche and prevent tissue overgrowth. These significant findings represent a novel concept in stem cell biology that an irreversibly committed cell that is downstream in a stem cell linage can become an essential regulator of stem cells. This project is supported by NYSTEM (contract# C023046 and C026427).

Hsu YC, Pasolli HA, Fuchs E. Dynamics between Stem Cells, Niche, and Progeny in the Hair Follicle. Cell. 2011 Jan 7;144(1): 92-105

NYSTEM Scientist Featured in NY Times

NYSTEM Scientist, Dr. Angela Christiano from Columbia University Medical Center, was featured in a recent article in the New York Times. Dr. Christiano is funded in her efforts at finding therapies for the treatment of epidermolysis bullosa, a fatal genetic skin disease (contract #C024321). Dr. Christiano´s other research focus is identifying the genetic causes of alopecia areata, a disease that leads to hair loss. Last year Dr. Christiano published the first genome-wide study identifying markers of the disease in a pool of patients. Surprisingly, alopecia is related to other well-known diseases including rheumatoid arthritis and type I diabetes. Understanding the genetic basis of diseases such as alopecia should lead to the development of new or improved therapies.

Cancer Stem Cells Produce Their Own Support Network

Work published in Nature by Viviane Tabar, M.D. and her colleagues at Memorial Sloan Kettering Cancer Center, shows that some cancer stem cells in glioblastomas (malignant brain tumors) become endothelial cells that form tumor blood vessels, vital to nourish tumor growth. The tumor-derived blood vessels do not respond to current anti-angiogenesis drugs such as Avastin. Research from another group published in the same issue showed that these tumor-derived blood vessels are crucial to tumor survival. Thus, the finding that tumors evade destruction by contributing to their own support system expands the known roles of cancer stem cells and identifies a novel target for therapeutic development. Moreover, the work suggests important questions for future research: What other tumor support cells are derived from cancer stem cells? How general is the differentiation of cancer stem cells into endothelial cells? What mechanism directs cancer stem cell endothelial differentiation? Answers to these questions should aid the search for more effective cancer treatment.

Original Article:
Glioblastoma stem-like cells give rise to tumour endothelium. Wang R, Chadalavada K, Wilshire J, Kowalik U, Hovinga KE, Geber A, Fligelman B, Leversha M, Brennan C, Tabar V. Nature 2010 Dec 9; 468 (7325): 829-33. Epub 2010 Nov 21

News & Views:
Cancer: Tumour stem cells switch sides. Victoria L. Bautch
Nature 2010 Dec 9; 468 (7325): 770–771

NYSTEM scientist featured on The Scientist's Naturally Selected

Gord Fishell, of the NYU School of Medicine, received a NYSTEM IIRP award (contract #C024236) for his work on directing differentiating mouse embryonic stem (ES) cells into specific subtypes of cortical interneurons. Interneurons are one of the two types of neurons found in the brain. Interneurons are inhibitory neurons that decrease electrical activity. While both types of neurons are required for proper brain function, a decrease in the function of interneurons can result in epileptic seizures, where excitatory waves of activity spread unchecked through the brain. The generation of interneurons from mouse ES cells provides a model system to develop treatments for epilepsy and other related diseases. In the Naturally Selected video, Dr. Fishell dicusses his lab's work on how a small number of cells in the developing brain can produce over 100 different types of interneurons in the adult brain.

NYSTEM supports research showing blood vessels are key to liver regeneration

New data from the lab of Shahin Rafii, M.D., at Weill Cornell Medical College, was recently published in Nature. Dr. Rafii´s group found that endothelial cells, which line blood vessels, secrete growth factors that spur liver stem cells, called hepatocytes, to proliferate and regenerate liver in mice. Prior to this report, the role of endothelial cells was completely overlooked in liver regeneration. Previous efforts to transplant hepatocytes alone have mostly failed, probably because no endothelial cells were transplanted with the hepatocytes. Liver diseases cause the death of more than 60,000 people each year in the US, so combining the two cell types together might help regenerate and heal damaged livers, substantially reducing this number. Preliminary evidence from Dr. Rafii´s lab suggests endothelial cells may contribute to tissue regeneration in additional tissues as well. This project is supported by NYSTEM (contract #C024180).

Ding BS, Nolan DJ, Butler JM, James D, Babazadeh AO, Rosenwaks Z, Mittal V, Kobayashi H, Shido K, Lyden D, Sato TN, Rabbany SY, Rafii S. Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration. Nature . 2010 Nov 11;468(7321):310-5.

NYSTEM Funds Research to Grow Joints by Stem Cell Homing

The research findings published early online in The Lancet by Jeremy Mao, Ph.D., at Columbia University Medical Center, along with his colleagues at the University of Missouri and Clemson University, have laid the groundwork for possible future joint replacement for patients with diseased or damaged joints. The regenerated joints consist of biodegradable materials which were shaped into anatomically correct scaffolds with a bioprinter. The scaffolds, which were then infused with a protein called transforming growth factor TGFβ3, were implanted and yielded fully regenerated hyaline cartilage in the articular surface after 4 months in rabbit model. Besides the world’s first fully regenerated biological joint, the Columbia team was able to bioengineer articular cartilage and supporting bone from the host’s endogenous stem cells in a process dubbed as ‘homing’. It is hoped that in the coming years, regenerated joint analogs will potentially replace current metal and plastic joints. This project is supported by NYSTEM (contract# C024336).

Lee CH, Cook JL, Mendelson A, Moioli EK, Yao H, Mao JJ. Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study.
Lancet. 2010 Aug 7;376(9739):440-8