Fall 2014 PS-OC newsletter online

The most recent newsletter from Johns Hopkins Physical Sciences-Oncology Center (PS-OC) is now online for your reading pleasure. One of the best features of this little update is the extensive list of recently published papers with brief summaries of each. It is a full rundown of what this center has been working on since April 2014.

Screen Shot 2014-09-23 at 12.55.23 PMThe Johns Hopkins Physical Sciences-Oncology Center is one of several NCI-funded PS-OC’s launched to better understand and control cancer through initiatives that enable the convergence of the physical sciences with cancer biology.

Click on this link to download your very own pdf copy.

For more information about the Johns Hopkins PS-OC go to http://psoc.inbt.jhu.edu/

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, mspiro@jhu.edu or 410-516-4802.

“Cells Performing Secret Handshake” wins grand prize

Sebastian F. Barreto, a doctoral student of chemical and biomolecular engineering in the laboratory of Sharon Gerecht, won the grand prize for his image “Cells Performing Secret Handshake” from the Regenerative Medicine Foundation. Another image that Barreto submitted received 3rd place (shown below), and a third image received honorable mention.

Late last year, RMF issued an international call for macro-photography of regenerative medicine images taken through a microscope. This inaugural contest resulted in nearly 100 images representing scientists from the United States, Australia, Canada, Germany, the Netherlands and the United Kingdom.

Cells-Performing-Secret-Handshakes

This image by Sebastian Barreto of Human Umbilical Vein Endothelial Cells “performing a secret handshake” won the grand prize in the first photo contest of the Regenerative Medicine Foundation.

Barreto’s image was included in the “Art of Science: Under the Surface” exhibition that featured an opening lecture and public reception with global expert in regenerative medicine Anthony Atala, M.D. and award winning photographer, painter and sculpture, Kelly Milukas, whose talk focused on the impact of art on healing. The winning images will also be featured in a special public patron gallery exhibition component during the Regenerative Medicine Foundation annual meeting held in San Francisco, May 5-7, 2014.

In a congratulatory letter, Joan F. Schanck, the Academic Research Program Officer, Wake Forest Institute for Regenerative Medicine and Director of Education for the Regenerative Medicine Foundation, said, “This competition will assist in developing a digital library that can be used to excite, inform and educate a broad audience.”

Barreto is affiliated with both the Johns Hopkins Institute for NanoBioTechnology and with the Physical Sciences-Oncology Center.

Captions for both photos can be found below:

Technical description for the grand prize photo: Epifluorescence image was taken at 1280 x 1024 using an Olympus BX60 microscope. Human Umbilical Vein Endothelial Cells (HUVECs) were cultured for five days and stained for F-actin (green), Vascular Endothelial cadherin (VEcad; red), and nuclei was counter-stained with DAPI (blue).

 

Endothelial-Cells-Resisting-Smooth-Muscle-Cell-Pull

Barreto’s image of endothelial cells won 3rd place in the RMF photo contest.

 

Technical description for 3rd place photo: Epifluorescence image was taken at 1280 x 1024 using an Olympus BX60 microscope. Human Endothelial Colony Forming Cells (ECFCs) were cultured for eight days before being co-cultured with human Smooth Muscle Cells (SMCs) for four more days. ECFCs were stained with CD31 (red), SMCs with SM22 (green), and nuclei was counterstained with DAPI (blue).

 

 

 

Cancer spreads through ‘Rock’ and ‘Rho’

n low oxygen conditions, breast cancer cells form structures that facilitate movement, such as filaments that allow the cell to contract (green) and cellular ‘hands’ that grab surfaces to pull the cell along (red). Credit: Daniele Gilkes

In low oxygen conditions, breast cancer cells form structures that facilitate movement, such as filaments that allow the cell to contract (green) and cellular ‘hands’ that grab surfaces to pull the cell along (red).
Credit: Daniele Gilkes

ROCK1 and RhoA genes found partly to blame for cancer metastasis. Gregg Semenza, co-director of the Johns Hopkins Physical Sciences-Oncology Center (PS-OC), led a team that made the discovery. The following comes from a Johns Hopkins press release:

Biologists at The Johns Hopkins University have discovered that low oxygen conditions, which often persist inside tumors, are sufficient to initiate a molecular chain of events that transforms breast cancer cells from being rigid and stationary to mobile and invasive. Their evidence, published online in Proceedings of the National Academy of Sciences on Dec. 9, underlines the importance of hypoxia-inducible factors in promoting breast cancer metastasis.

“High levels of RhoA and ROCK1 were known to worsen outcomes for breast cancer patients by endowing cancer cells with the ability to move, but the trigger for their production was a mystery,” says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine and senior author of the article. “We now know that the production of these proteins increases dramatically when breast cancer cells are exposed to low oxygen conditions.”

To move, cancer cells must make many changes to their internal structures, Semenza says. Thin, parallel filaments form throughout the cells, allowing them to contract and cellular “hands” arise, allowing cells to “grab” external surfaces to pull themselves along. The proteins RhoA and ROCK1 are known to be central to the formation of these structures.

Moreover, the genes that code for RhoA and ROCK1 were known to be turned on at high levels in human cells from metastatic breast cancers. In a few cases, those increased levels could be traced back to a genetic error in a protein that controls them, but not in most. This activity, said Semenza, led him and his team to search for another cause for their high levels.

What the study showed is that low oxygen conditions, which are frequently present in breast cancers, serve as the trigger to increase the production of RhoA and ROCK1 through the action of hypoxia-inducible factors.

“As tumor cells multiply, the interior of the tumor begins to run out of oxygen because it isn’t being fed by blood vessels,” explains Semenza. “The lack of oxygen activates the hypoxia-inducible factors, which are master control proteins that switch on many genes that help cells adapt to the scarcity of oxygen.” He explains that, while these responses are essential for life, hypoxia-inducible factors also turn on genes that help cancer cells escape from the oxygen-starved tumor by invading blood vessels, through which they spread to other parts of the body.

Daniele Gilkes, Ph.D., a postdoctoral fellow at the PS-OC and lead author of the report, analyzed human metastatic breast cancer cells grown in low oxygen conditions in the laboratory. She found that the cells were much more mobile in the presence of low levels of oxygen than at physiologically normal levels. They had three times as many filaments and many more “hands” per cell. When the hypoxia-inducible factor protein levels were knocked down, though, the tumor cells hardly moved at all. The numbers of filaments and “hands” in the cells and their ability to contract were also decreased.

When Gilkes measured the levels of the RhoA and ROCK1 proteins, she saw a big increase in the levels of both proteins in cells grown in low oxygen. When the breast cancer cells were modified to knock down the amount of hypoxia-inducible factors, however, the levels of RhoA and ROCK1 were decreased, indicating a direct relationship between the two sets of proteins. Further experiments confirmed that hypoxia-inducible factors actually bind to the RhoA and ROCK1 genes to turn them on.

The team then took advantage of a database that allowed them to ask whether having RhoA and ROCK1 genes turned on in breast cancer cells affected patient survival. They found that women with high levels of RhoA or ROCK1, and especially those women with high levels of both, were much more likely to die of breast cancer than those with low levels.

“We have successfully decreased the mobility of breast cancer cells in the lab by using genetic tricks to knock the hypoxia-inducible factors down,” says Gilkes. “Now that we understand the mechanism at play, we hope that clinical trials will be performed to test whether drugs that inhibit hypoxia-inducible factors will have the double effect of blocking production of RhoA and ROCK1 and preventing metastases in women with breast cancer.”

Other authors of the report include Lisha Xiang, Sun Joo Lee, Pallavi Chaturvedi, Maimon Hubbi and Denis Wirtz of the Johns Hopkins University School of Medicine.

This work was supported by grants from the National Cancer Institute (U54-CA143868), the Johns Hopkins Institute for Cell Engineering, the American Cancer Society and the Susan G. Komen Breast Cancer Foundation.

Studying cells in 3D, the way it should be

When scientists experiment on cells in a flat Petri dish, it’s more been a matter of convenience than anything that recapitulates what that cell experiences in real life. Johns Hopkins professor Denis Wirtz for some time has been growing and studying cells three dimensions, rather than the traditional two dimensions. And pretty much, he’s discovered that a lot of what we think we know about cells is dead wrong.

cancer-in-3d-impact_0

Cell in 3D. Image by Anjil Giri/Wirtz Lab

In this recent article by Johns Hopkins writer Dale Keiger, you will discover what Wirtz has discovered through his investigations. Furthermore, you will find out about the man behind these revolutionary ideas that are turning basic cell biology upside-down, as well as challenge a lot of what we thought we understood about diseases like cancer.

Wirtz directs the Johns Hopkins Physical-Sciences Oncology Center and is associate director and co-founder of Johns Hopkins Institute for NanoBioTechnology. He recently launched the Center for Digital Pathology. He is a the Theophilus Halley Smoot professor of chemical and biomolecular engineering.

You can read the entire magazine article “Moving cancer research out of the Petri dish and into the third dimension” online here at the JHU Hub.

Game Theory and Cancer

What does game theory and cancer have to do with each other. I am not sure but this interesting workshop hosted by the Princeton Physical Sciences-Oncology Center and Johns Hopkins University might help you figure that out.

An announcement about the event reads:

Screen Shot 2013-08-02 at 12.03.06 PMRegistration is now open for the Workshop on Game Theory and Cancer, scheduled on August 12-13 in Baltimore, MD, and jointly hosted by our Princeton PS-OC and Johns Hopkins University. The main goal of this workshop is to provide a dialogue between leading basic researchers and clinical investigators that would help make headway against the very stubborn problem of cancer, and to jolt the oncology community into confronting the serious clinical problems that have previously been avoided.

The flyer is pretty cool, too.  Check it out here.

Additional information and preliminary agenda can be found at: http://www.princeton.edu/psoc/training/

To register, please go to: https://prism.princeton.edu/ps-oc/regform.php

For questions about the event, email maranzam@princeton.edu or sclam@princeton.edu

Fraley nets $500K Burroughs Wellcome Fund award for microfluidics work

Stephanie Fraley (Photo: Homewood Photography)

Stephanie Fraley (Photo: Homewood Photography)

A Johns Hopkins research fellow who is developing novel approaches to quickly identify bacterial DNA and human microRNA has won the prestigious $500,000 Burroughs Wellcome Fund (BWF) Career Award at the Scientific Interfaces. The prize, distributed over the next five years, helps transition newly minted PhDs from postdoctoral work into their first faculty positions.

Stephanie Fraley is a postdoctoral fellow working with Samuel Yang, MD, in Emergency Medicine/Infectious Disease at the Johns Hopkins School of Medicine and Jeff Wang, PhD, in Biomedical Engineering with appointments in the Whiting School of Engineering and the medical school. The goal of her work is to develop engineering technologies that can diagnose and guide treatment of sepsis, a leading cause of death worldwide, while simultaneously leading to improved understanding of how human cells and bacterial cells interact.

“Sepsis is an out of control immune response to infection,” Fraley said. “We are developing tools that are single molecule sensitive and can rapidly sort and detect bacterial and host response markers associated with sepsis. However, our devices are universal in that they can be applied to many other diseases.”

Fraley is using lab-on-chip technology, also known as microfluidics, to overcome the challenges of identifying the specific genetic material of bacteria and immune cells. Her technology aims to sort the genetic material down to the level of individual sequences so that each can be quantified with single molecule sensitivity.

“Bacterial DNA is on everything and contamination is everywhere, so trying to find the ones associated with sepsis is like the proverbial search for the needle in the haystack,” Fraley said. “With microfluidics, we can separate out all the bacterial DNA, so instead of a needle in a haystack, we have just the needles.”

Another advantage to Fraley’s novel technology is that it will assess all the diverse bacterial DNA present in a sample, without presuming which genetic material is important. “Bacteria are constantly evolving and becoming drug resistant,” she said. “With this technology, we can see all the bacterial DNA that is present individually and not just the strains we THINK we need to look for.”

Fraley’s award will follow her wherever her career takes her. The first two years of the prize fund postdoctoral training and that last three years help launch her professional career in academia. During the application process, she had to make a short presentation on her proposal to BWF’s panel of experts. “It was like the television show ‘Shark Tank’ but for scientists,” she laughs. “ The panelists gave me many helpful suggestions on my idea.”

Fraley earned her bachelor’s degree in chemical engineering from the University of Tennessee at Chattanooga and her doctorate in chemical and biomolecular engineering with Denis Wirtz, professor and director of Johns Hopkins Physical Sciences-Oncology Center. Wirtz is associate director for the Institute for NanoBioTechnology and Yang and Wang also are INBT affiliated faculty members.

BWF’s Career Awards at the Scientific Interface provides funding to bridge advanced postdoctoral training and the first three years of faculty service. These awards are intended to foster the early career development of researchers who have transitioned or are transitioning from undergraduate and/or graduate work in the physical/mathematical/computational sciences or engineering into postdoctoral work in the biological sciences, and who are dedicated to pursuing a career in academic research. These awards are open to U.S. and Canadian citizens or permanent residents as well as to U.S. temporary residents.

Landmark physical characterization of cancer cells completed

An enormous collaborative effort between a multitude of academic and research centers has characterized numerous physical and mechanical properties on one identical human cancer cell line. Their two-year cooperative study, published online in the April 26, 2013 journal Science Reports, reveals the persistent and agile nature of human cancer cells as compared to noncancerous cells. It also represents a major shift in the way scientific research can be accomplished.

Human breast cancer cells like these were used in the study. (Image created by Shyam Khatau/ Wirtz Lab)

Human breast cancer cells like these were used in the study. (Image created by Shyam Khatau/ Wirtz Lab)

The research, which was conducted by 12 federally funded Physical Sciences-Oncology Centers (PS-OC) sponsored by the National Cancer Institute, is a systematic comparison of metastatic human breast-cancer cells to non-metastatic breast cells that reveals dramatic differences between the two cell lines in their mechanics, migration, oxygen response, protein production and ability to stick to surfaces. They have also discovered new insights into how human cells make the transition from nonmalignant to metastatic, a process that is not well understood.

Denis Wirtz, a Johns Hopkins professor of chemical and biomolecular engineering with joint appointments in pathology and oncology who is the corresponding author on the study, remarked that the work adds a tremendous amount of information about the physical nature of cancer cells. “For the first time ever, scientists got together and have created THE phenotypic signature of cancer” Wirtz said. “Yes, it was just one metastatic cell line, and it will require validation with many other cell lines. But we now have an extremely rich signature containing many parameters that are distinct when looking at metastatic and nonmetastatic cells.”

Wirtz, who directs the Johns Hopkins Physical Sciences-Oncology Center, also noted the unique way in which this work was conducted: all centers used the same human cell line for their studies, which makes the quality of the results unparalleled. And, since human and not animal cells were used, the findings are immediately relevant to the development of drugs for the treatment of human disease.

“Cancer cells may nominally be derived from the same patient, but in actuality they will be quite different because cells drift genetically over just a few passages,” Wirtz said.  “This makes any measurement on them from different labs like comparing apples and oranges.” In this study, however, the genetic integrity of the cell lines were safeguarded by limiting the number times the original cell cultures could be regrown before they were discarded.

The nationwide PS-OC brings together researchers from physics, engineering, computer science, cancer biology and chemistry to solve problems in cancer, said Nastaran Zahir Kuhn, PS-OC program manager at the National Cancer Institute.

“The PS-OC program aims to bring physical sciences tools and perspectives into cancer research,” Kuhn said. “The results of this study demonstrate the utility of such an approach, particularly when studies are conducted in a standardized manner from the beginning.”

For the nationwide project, nearly 100 investigators from 20 institutions and laboratories conducted their experiments using the same two cell lines, reagents and protocols to assure that results could be compared. The experimental methods ranged from physical measurements of how the cells push on surrounding cells to measurements of gene and protein expression.

“Roughly 20 techniques were used to study the cell lines, enabling identification of a number of unique relationships between observations,” Kuhn said.

Wirtz added that it would have been logistically impossible for a single institution to employ all of these different techniques and to measure all of these different parameters on just one identical cell line. That means that this work accomplished in just two years what might have otherwise taken ten, he said.

The Johns Hopkins PS-OC made specific contributions to this work. Using particle-tracking microrheology, in which nanospheres are embedded in the cell’s cytoplasm and random cell movement is visually monitored, they measured the mechanical properties of cancerous versus noncancerous cells. They found that highly metastatic breast cancer cells were mechanically softer and more compliant than cells of less metastatic potential.

Using 3D cell culturing techniques, they analyzed the spontaneous migratory potential (that is, migration without the stimulus of any chemical signal) of cancerous versus noncancerous cells. They also analyzed the extracellular matrix molecules that were deposited by the two cell lines and found that cancerous cells deposited more hyaluronic acid (HA). The HA, in turn, affects motility, polarization and differentiation of cells.  Finally, the Hopkins team measured the level of expression of CD44, a cell surface receptor that recognizes HA, and found that metastatic cells express more CD44.

The next steps, Wirtz said, would be to validate these results using other metastatic cell lines.  To read the paper, which is published in an open access journal, follow this link: http://www.nature.com/srep/2013/130422/srep01449/full/srep01449.html

Excerpts from original press release by Princeton science writer Morgan Kelly were used.

 

 

 

 

Recent publications from the Johns Hopkins Physical Sciences-Oncology Center

Johns Hopkins Physical Sciences-Oncology Center has had a productive quarter publishing from February to May 2013. Here are some of the most recent publications in support or the center’s core research projects, including a huge collaborative work drawing on the knowledge and research findings of the entire PS-OC network.

Screen Shot 2013-05-15 at 4.27.37 PMThat paper, A physical sciences network characterization of non-tumorigenic and metastatic cells, was the work of 95 authors from all 12 of the National Cancer Institute’s PS-OC  program centers. JHU’s PS-OC director Denis Wirtz, the Theophilus H. Smoot Professor in the Johns Hopkins Department of Chemical and Ciomolecular Engineering, is the corresponding author on this massive effort. We will be discussing the findings of that paper in a future post here on the PS-OC website. Until then, here is a link to that network paper and 13 other recent publications from the Johns Hopkins PS-OC.

  • A physical sciences network characterization of non-tumorigenic and metastatic cells.Physical Sciences – Oncology Centers Network, Agus DB, Alexander JF, Arap W,Ashili S, Aslan JE, Austin RH, Backman V, Bethel KJ, Bonneau R, Chen WC,Chen-Tanyolac C, Choi NC, Curley SA, Dallas M, Damania D, Davies PC, Decuzzi P,Dickinson L, Estevez-Salmeron L, Estrella V, Ferrari M, Fischbach C, Foo J,Fraley SI, Frantz C, Fuhrmann A, Gascard P, Gatenby RA, Geng Y, Gerecht S,Gillies RJ, Godin B, Grady WM, Greenfield A, Hemphill C, Hempstead BL, HielscherA, Hillis WD, Holland EC, Ibrahim-Hashim A, Jacks T, Johnson RH, Joo A, Katz JE,Kelbauskas L, Kesselman C, King MR, Konstantopoulos K, Kraning-Rush CM, Kuhn P,Kung K, Kwee B, Lakins JN, Lambert G, Liao D, Licht JD, Liphardt JT, Liu L, LloydMC, Lyubimova A, Mallick P, Marko J, McCarty OJ, Meldrum DR, Michor F,Mumenthaler SM, Nandakumar V, O’Halloran TV, Oh S, Pasqualini R, Paszek MJ,Philips KG, Poultney CS, Rana K, Reinhart-King CA, Ros R, Semenza GL, Senechal P,Shuler ML, Srinivasan S, Staunton JR, Stypula Y, Subramanian H, Tlsty TD, TormoenGW, Tseng Y, van Oudenaarden A, Verbridge SS, Wan JC, Weaver VM, Widom J, Will C, Wirtz D, Wojtkowiak J, Wu PH.  Sci Rep. 2013 Apr 25;3:1449. doi:10.1038/srep01449. PubMed PMID: 23618955; PubMed Central PMCID: PMC3636513. http://www.ncbi.nlm.nih.gov/pubmed/23618955
  • Procollagen Lysyl Hydroxylase 2 Is Essential for Hypoxia-Induced Breast Cancer Metastasis. Gilkes DM, Bajpai S, Wong CC, Chaturvedi P, Hubbi ME, Wirtz D, Semenza GL.Mol Cancer Res. 2013 May 7. [Epub ahead of print] PubMed PMID: 23378577. http://www.ncbi.nlm.nih.gov/pubmed/23378577
  • Predicting how cells spread and migrate: Focal adhesion size does matter. Kim DH, Wirtz D. Cell Adh Migr. 2013 Apr 29;7(3). [Epub ahead of print] PubMed PMID: 23628962. http://www.ncbi.nlm.nih.gov/pubmed/23628962
  • Hypoxia-inducible Factor 1 (HIF-1) Promotes Extracellular Matrix Remodeling under Hypoxic Conditions by Inducing P4HA1, P4HA2, and PLOD2 Expression in Fibroblasts. Gilkes DM, Bajpai S, Chaturvedi P, Wirtz D, Semenza GL. J Biol   Chem. 2013 Apr 12;288(15):10819-29. doi: 10.1074/jbc.M112.442939. Epub 2013 Feb 19. PubMed PMID: 23423382; PubMed Central PMCID: PMC3624462. http://www.ncbi.nlm.nih.gov/pubmed/23423382
  • Perivascular cells in blood vessel regeneration. Wanjare M, Kusuma S, Gerecht S. Biotechnol J. 2013 Apr;8(4):434-47. doi: 10.1002/biot.201200199. PubMed PMID: 23554249. http://www.ncbi.nlm.nih.gov/pubmed/23554249
  • Focal adhesion size uniquely predicts cell migration. Kim DH, Wirtz D. FASEB J. 2013 Apr;27(4):1351-61. doi: 10.1096/fj.12-220160. Epub 2012 Dec 19. PubMed PMID: 23254340; PubMed Central PMCID: PMC3606534. http://www.ncbi.nlm.nih.gov/pubmed/23254340
  • Notch4-dependent Antagonism of Canonical TGFβ1  Signaling Defines Unique Temporal Fluctuations of SMAD3 Activity in Sheared Proximal Tubular Epithelial Cells. Grabias BM, Konstantopoulos K. Am J Physiol Renal Physiol. 2013 Apr 10. [Epub ahead of print] PubMed PMID: 23576639. http://www.ncbi.nlm.nih.gov/pubmed/23576639
  • Integration and regression of implanted engineered human vascular networks during deep wound healing. Hanjaya-Putra D, Shen YI, Wilson A, Fox-Talbot K, Khetan S, Burdick JA, Steenbergen C, Gerecht S. Stem Cells Transl Med. 2013 Apr;2(4):297-306. doi: 10.5966/sctm.2012-0111. Epub 2013 Mar 13. PubMed PMID: 23486832. http://www.ncbi.nlm.nih.gov/pubmed/23486832
  • Collagen Prolyl Hydroxylases are Essential for Breast Cancer Metastasis. Gilkes DM, Chaturvedi P, Bajpai S, Wong CC, Wei H, Pitcairn S, Hubbi ME, Wirtz D, Semenza GL. Cancer Res. 2013 Mar 28. [Epub ahead of print] PubMed PMID: 23539444. http://www.ncbi.nlm.nih.gov/pubmed/23539444
  • Simultaneously defining cell phenotypes, cell cycle, and chromatin modifications at single-cell resolution.Chambliss AB, Wu PH, Chen WC, Sun SX, Wirtz D.FASEB J. 2013 Mar 28. [Epub ahead of print] PubMed PMID: 23538711.http://www.ncbi.nlm.nih.gov/pubmed/23538711
  • Interstitial friction greatly impacts membrane mechanics. Wirtz D. Biophys J.2013 Mar 19;104(6):1217-8. doi: 10.1016/j.bpj.2013.02.003. Epub 2013 Mar 19.PubMed PMID: 23528079; PubMed Central PMCID: PMC3602747.http://www.ncbi.nlm.nih.gov/pubmed/23528079
  • Functional interplay between the cell cycle and cell phenotypes. Chen WC, Wu PH, Phillip JM, Khatau SB, Choi JM, Dallas MR, Konstantopoulos K,Sun SX, Lee JS, Hodzic D, Wirtz D.Integr Biol (Camb). 2013 Mar;5(3):523-34. doi:10.1039/c2ib20246h. PubMed PMID: 23319145 http://www.ncbi.nlm.nih.gov/pubmed/23319145
  • High-throughput secretomic analysis of single cells to assess functional cellular heterogeneity. Lu Y, Chen JJ, Mu L, Xue Q, Wu Y, Wu PH, Li J, Vortmeyer AO, Miller-Jensen K, Wirtz D, Fan R. Anal Chem. 2013 Feb 19;85(4):2548-56. doi:10.1021/ac400082e. Epub 2013 Feb 1. PubMed PMID: 23339603; PubMed Central PMCID:  PMC3589817.http://www.ncbi.nlm.nih.gov/pubmed/23339603\

 

INBT engineers coax stem cells to diversify

Growing new blood vessels in the lab is a tough challenge, but a Johns Hopkins engineering team has solved a major stumbling block: how to prod stem cells to become two different types of tissue that are needed to build tiny networks of veins and arteries.

The team’s solution is detailed in an article appearing in the January 2013 print edition of the journal Cardiovascular Research. The article also was published recently in the journal’s online edition. The work is important because networks of new blood vessels, assembled in the lab for transplanting into patients, could be a boon to people whose circulatory systems have been damaged by heart disease, diabetes and other illnesses.

blood-vessel-3-72

Illustration by Maureen Wanjare

“That’s our long-term goal—to give doctors a new tool to treat patients who have problems in the pipelines that carry blood through their bodies,” said Sharon Gerecht, an assistant professor of chemical and biomolecular engineering who led the research team. “Finding out how to steer these stem cells into becoming critical building blocks to make these blood vessel networks is an important step.”

In the new research paper, the Gerecht team focused on vascular smooth muscle cells, which are found within the walls of blood vessels. Two types have been identified: synthetic smooth muscle cells, which migrate through the surrounding tissue, continue to divide and help support the newly formed blood vessels; and contractile smooth muscles cells, which remain in place, stabilize the growth of new blood vessels and help them maintain proper blood pressure.

To produce these smooth muscle cells, Gerecht’s lab has been experimenting with both National Institutes of Health-approved human embryonic stem cells and induced pluripotent stem cells. The induced pluripotent stem cells are adult cells that have been genetically reprogrammed to act like embryonic stem cells. Stem cells are used in this research because they possess the potential to transform into specific types of cells needed by particular organs within the body.

In an earlier study supervised by Gerecht, her team was able to coax stem cells to become a type of tissue that resembled smooth muscle cells but didn’t quite behave properly. In the new experiments, the researchers tried adding various concentrations of growth factor and serum to the previous cells. Growth factor is the “food’ that the cells consume; serum is a liquid component that contains blood cells.

“When we added more of the growth factor and serum, the stem cells turned into synthetic smooth muscle cells,” Gerecht said. “When we provided a much smaller amount of these materials, they became contractile smooth muscles cells.”

This ability to control the type of smooth muscle cells formed in the lab could be critical in developing new blood vessel networks, she said. “When we’re building a pipeline to carry blood, you need the contractile cells to provide structure and stability,” she added. “But in working with very small blood vessels, the migrating synthetic cells can be more useful.”

In cancer, small blood vessels are formed to nourish the growing tumor. The current work could also help researchers understand how blood vessels are stabilized in tumors, which could be useful in the treatment of cancer.

“We still have a lot more research to do before we can build complete new blood vessel networks in the lab,” Gerecht said, “but our progress in controlling the fate of these stem cells appears to be a big step in the right direction.”

In addition to her faculty appointment with Johns Hopkins’ Whiting School of Engineering, Gerecht is affiliated with the university’s Institute for NanoBioTechnology (INBT) and the Johns Hopkins Engineering in Oncology Center.

The lead author of the new Cardiovascular Research paper is Maureen Wanjare, a doctoral student in Gerecht’s lab who is supported both by the INBT, through a National Science Foundation Integrative Graduate Education and Research Traineeship, and by the NIH. Coauthors of the study are Gerecht and Frederick Kuo, who participated in the research as an undergraduate majoring in chemical and biomolecular engineering. The human induced pluripotent stem cells used in the study were provided by Linzhao Cheng, a hematology professor in the Johns Hopkins School of Medicine.

This research was supported by an American Heart Association Scientist Development Grant and NIH grant R01HL107938.

Original press release can be found here.

 

Breast cancer patient advocates offer insight

Researchers are tapping into the first-hand knowledge of survivors of breast cancer through the cancer patient advocate program at Johns Hopkins Physical Sciences-Oncology Center (PS-OC).

“Breast cancer patients can provide valuable insight into the impact of therapies,” said Abigail Hielscher, a chemical and biomolecular engineering postdoctoral fellow in the Sharon Gerecht laboratory. Hielscher is helping to organize an effort to locate breast cancer survivors and patients, as well as those who work closely with them such as oncology nurses, to inform the efforts of researchers developing cancer diagnosis and treatments.

In addition to acting as a liaison between the population of breast cancer survivors and patients and the community of Johns Hopkins PS-OC scientists performing breast cancer-related research, patient advocates also are charged with telling the public and funding agencies about the latest breast cancer research being performed in PS-OC labs.

Likewise, researchers must communicate their findings via laboratory demonstrations and brief, non-technical talks to the breast cancer advocates.

“Survivors can facilitate communication between those directly affected by the disease and those working to treat or cure it,” Hielscher said. “The advocates, both patients and nurses, allow researchers to better understand and implement the needs of breast cancer patients in terms of new therapies and treatment strategies.”

Cancer patient advocates meet periodically with Johns Hopkins PS-OC researchers. Currently, PS-OC patient advocates are Mary Capano, MSN, RN, CBPN-IC and Nancy Cardwell.

If you or someone you know is a breast cancer survivor who would like to learn about the volunteer opportunity as a patient advocate contact Abigail Hielscher at ahielsc1@jhu.edu or via phone: 402-889-0283.