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\

 

Spring nano-bio mini-symposium set for April 3

Catch up on the latest research happening in Johns Hopkins University labs working in nanobiotechnology, the physics of cancer and cancer nanotech at INBT’s spring mini-symposium Wednesday, April 3 from 9 a.m. to 1 p.m. in Leverings’s Great Hall on the Homewood campus.

AT AT GLANCE- INBT new signSMALL

Mini-symposiums are organized in the spring and fall by student leaders in the Johns Hopkins Institute for NanoBioTechnology, the Engineering in Oncology Center and the Center of Cancer Nanotechnology Excellence. They are a means of showcasing current work, learning from guest speakers and facilitating communication and collaboration among affiliated laboratories. This event is open to the entire Johns Hopkins Community. Save the date!

The agenda is as follows:

  • 9:00 am ~ 9:10 am Welcome speech Denis Wirtz, PhD, Director of Johns Hopkins Physical Science Oncology Center (PS-OC)
  • 9:10 am ~ 9:40 am “Role of ion channels and aquaporins in cancer cell migration in confined microenvironments” Kimberly M. Stroka, PhD, Postdoc fellow (PS-OC) Department of Chemical and Biomolecular Engineering, Johns Hopkins University
  • 9:40 am ~ 10:10 am “TBD” Helena Zec, Graduate student (CCNE) Department of Biomedical Engineering, Johns Hopkins University
  • 10:10 am ~ 10:40 am “Single-cell protein profiling to study cancer cell heterogeneity” Jonathan Chen, Graduate student (PS-OC) Department of Biomedical Engineering, Yale University
  • 10:40 am ~ 11:30 am “Synthetic cell biology: total synthesis of cellular functions” Takanari Inoue, PhD, Assistant professor Department of Cell Biology, Johns Hopkins University School of Medicine
  • 11:30 am ~ 11:40 am Coffee Break
  • 11:40 am ~ 12:10 pm “TBD” Yu-Ja Huang, Graduate student (PS-OC) Department of Materials Science and Engineering, Johns Hopkins University
  • 12:10 pm ~ 1:00 pm “Infections, Chronic Inflammation, and Prostate Cancer” Karen Sandell Sfanos, PhD, Assistant professor Department of Pathology, Johns Hopkins University School of Medicine
  • 1:00 pm ~ 1:30 pm “Development of CEST liposomes for monitoring nanoparticle-based cancer therapies using MRI” Tao Yu, Graduate student (CCNE) Department of Biomedical Engineering, Johns Hopkins University

INBT Spring mini-symposium flyer

Molecular culprit linked to breast cancer spread

Johns Hopkins researchers have uncovered a protein “partner” commonly used by breast cancer cells to unlock genes needed for spreading the disease around the body. A report on the discovery, published Nov. 5 on the website of the Proceedings of the National Academy of Sciences, details how some tumors get the tools they need to metastasize.

“We’ve identified a protein that wasn’t known before to be involved in breast cancer progression,” says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine and director of the Vascular Program at the university’s Institute for Cell Engineering. “The protein JMJD2C is the key that opens up a whole suite of genes needed for tumors to grow and metastasize, so it represents a potential target for cancer drug development.” Semenza also is associate director of the Johns Hopkins Physical Sciences-Oncology Center.

Semenza and his colleagues made their finding when they traced the activity of HIF-1, a protein known to switch on hundreds of genes involved in development, red blood cell production, and metabolism in normal cells. Previous studies had shown that HIF-1 could also be hijacked to switch on genes needed to make breast tumors more malignant.

Would-be tumor cells face a host of challenges as they make the transition from working with their host to working against it, such as the need to evade the immune system and to produce more cancer cells, explains Weibo Luo, Ph.D., an instructor in the Institute for Cell Engineering and Department of Biological Chemistry who led the project. All of these efforts require switching on the right genes for the job.

To learn more about how HIF-1 works, the researchers tested a range of human proteins to see whether they would interact with HIF-1. They then sifted through the 200 resulting hits, looking for proteins involved in chemical changes to sections of DNA that determine whether or not the genes they contain are available for use. “In order for HIF-1 to switch genes on, they have to be available, but many of the genes HIF-1 activates are normally locked down in mature cells,” explains Luo. “So we thought HIF-1 must have a partner that can do the unlocking.”

That partner turned out to be JMJD2C, Luo says. Delving deeper, the researchers found that HIF-1 switches on the JMJD2C gene, stimulating production of the protein. HIF-1′s presence also enables JMJD2C to bind to DNA at other HIF-1 target genes, and then loosen those DNA sections, enabling more HIF-1 to bind to the same sites and activate the target genes.

To test the implications of their discovery, the research team injected mice with breast cancer cells in which the JMJD2C protein was not produced. Tumors with depleted JMJD2C were much less likely to grow and metastasize to the lungs, confirming the protein’s role in breast cancer progression, says Luo.

“Active HIF proteins have been found in many types of tumors, so the implications of this finding go beyond breast cancer,” says Luo. “JMJD2C is both an important piece of the puzzle of how tumors metastasize, and a potential target for anti-cancer therapy.”

Other authors of the research report are Ryan Chang, Jun Zhong, Ph.D., and Akhilesh Pandey, M.D., Ph.D., all of the Johns Hopkins University School of Medicine.

This work was supported by grants from the National Heart, Lung, and Blood Institute (contracts N01-HV28180 and HHS-N268201000032C), and by funds from the Johns Hopkins Institute for Cell Engineering.

On the Web:

Johns Hopkins Physical Sciences-Oncology Center: http://psoc.inbt.jhu.edu/

Link to article: http://www.pnas.org/content/early/2012/10/31/1217394109.abstract

Semenza lab: http://www.hopkinsmedicine.org/institute_cell_engineering/experts/gregg_semenza.html

Q&A with Semenza: http://www.hopkinsmedicine.org/institute_cell_engineering/experts/meet_scientists/gregg_semenza.html

Original press release by Shawna WilliamsCatherine Kolf and Vanessa McMains

 

 

Meet INBT’s summer interns, already digging into their research

Research does not take a holiday during the summer at Johns Hopkins University in Baltimore, Md. In fact, it ramps up with the addition of many new faces from across the country.

The Johns Hopkins Institute for NanoBioTechnology summer research interns have arrived and are already busy at work in various laboratories. This year’s group is the largest the institute has ever hosted, with 17 undergraduates from universities nationwide.

Of the total, three students are affiliated with the Center of Cancer Nanotechnology Excellence and four are affiliated with the Physical Sciences-Oncology Center. The remaining 10 are part of the National Science Foundation Research Experience for Undergraduates program. All are hosted through INBT, which serves as a hub for their academic and social activities.

INBT summer interns conduct 10 weeks of research in a laboratory either on the Homewood or the medical campus of the University. At the end of that time, students have learned how to work in a multidisciplinary team and how to manage a short term research project.  They also discover if research is a pathway they want to pursue after earning their bachelor’s degrees.

In August, interns from many of the science, medicine, engineering and public health summer programs will gather for a  poster session to be held on August 2 at 3 p.m. in Turner Concourse. The poster session will allow students to show off the results of their their work.

This year’s INBT/PS-OC/CCNE interns include:

At the Whiting School of Engineering…

Amani Alkayyali from Wayne State University is an REU student in the laboratory of Honggang Cui assistant professor in the Department of Chemical and Biomolecular Engineering. Also in the Cui lab are CCNE intern Matthew Fong from the University of California, Berkeley and Michelle LaComb, an REU student from Rice University.

Sharon Gerecht, assistant professor in the Department of Chemical and Biomolecular engineering, is hosting three interns. Josh Porterfield of Cornell University and Carolyn Zhang from the University of California, San Diego are both PS-OC interns, and Bria Macklin of Howard University is an REU intern.

Jacqueline Carozza of Cornell University is a PS-OC student working in the lab of Denis Wirtz, professor in the Department Chemical and Biomolecular Engineering. Cassandra Loren from Oregon State University is a PS-OC intern also working in the Wirtz lab.

Eric Do from the University of Washington is an REU working in the lab of assistant professor Margarita Herrara-Alonso in the Department of Materials Science and Engineering.

Olivia Hentz from Cornell is an REU student working in the lab of Jonah Erlebacher, professor in the Department of Materials Science and Engineering.

Justin Samorajski from the University of Dallas is a returning summer intern, once again working in the materials science and engineering lab of professor Peter Searson as part of the CCNE.

At the School of Medicine…

Lauren Lee of Cornell University is an REU working in the lab of biomedical engineering lab of associate professor Hai-Quan Mao.

Albert Lu from the University of California Berkeley is a CCNE intern working in the biomedical engineering lab of associate professor Jeff Wang.

Bianca Lascano from Norfolk State University is an REU in assistant professor Jordan Green’s biomedical engineering lab.

Charlie Nusbaum of the Richard Stockton College is an REU intern in the radiation oncology lab of assistant professor Robert Ivkov.

At the Krieger School of Arts and Sciences…

Anthony Loder of Rowan University is an REU working in the biology lab of assistant professor Xin Chen.

Daniel McClelland is also REU from Bethany College works in the chemistry laboratory of professor Howard Fairbrother.