Undergraduate symposium showcases multidisciplinary research

Undergraduate students affiliated with Johns Hopkins Institute for NanoBioTechnology (INBT) laboratories hosted their annual research symposium on Nov 10 at the Homewood campus. Five students gave oral presentations and 30 students presented posters during the half-day event designed to showcase multidisciplinary work from across INBT affiliated laboratories.

Winners Allie Zito, Joey Li and Hayley Strasburger

Symposium winners Allie Zito, Joey Li and Hayley Strasburger.

Talks were given during the first part of the symposium. Oral presenters included Damian Cross and Aseem Jain, who shared a talk about Perileve: A novel method for refractory ascites; James Shamul, who spoke about a Novel Micellar Drug Delivery System using Poly (Beta-amino ester)-Poly (ethylene glycol) copolymer; Michael Pozin, who presented Heat Transfer Modeling for Femoroplasty Procedure; and Hayley Strasburger, who described how Noggin inhibits bmp signaling in oligodendrocytes progenitor cells to repress trans-differentiation into astrocytes.

During the second half of the symposium, poster presenters talked to volunteer judges comprised of INBT staff and alumni. There were three poster categories: concept, overall and crowd favorite. While the volunteer judges evaluated the first two groups, crowd favorite was voted on by every attendee by texting a poster number to a certain phone number. Winners included in the Concept category Victor Tang (1st) and Allie Zito (2nd). In the overall category, Hayley Strasburger (1st) and Joey Li (2nd) were the inners. Allie Zito also won crowd favorite.

15000596_10154704353192277_9071690777271476868_oThe event was funded by the Office of the Provost and given organizational support by INBT. Thanks and acknowledgement to everyone who came out to the symposium, to the judges who took time away from their work to provide feedback, the Office of the Provost for funding the event and to INBT, especially Camille Mathis, Ellie Boettinger-Heasley, Tom Fekete, and Gregg Nass.

 

 

 

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NCI grant establishes center to advance cancer curing goals

The National Cancer Institute has awarded Johns Hopkins Institute for NanoBioTechnology (INBT) a $9 million grant to support a multidisciplinary center to discover news ways to diagnose and treat cancer. NCI, which is part of the National Institutes for Health, allocated the funds over five years to enable scholars in the Johns Hopkins Physical Sciences-Oncology center to apply the tools of the physical scientist, engineer, applied mathematician, cancer biologist and others to unravel how cancer cells survive, grow and migrate.

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Artist’s image of a cancer cell traveling through a 3D matrix that closely resembles the environment through which cancer cells move in a human body. IMAGE CREDIT: JENNIFER E. FAIRMAN / DEPARTMENT OF ART AS APPLIED TO MEDICINE

The PS-OC is comprised of researchers from university’s Whiting School of Engineering and its School of Medicine, as well as collaborators from Washington University in Saint Louis, the University of Pennsylvania Abramson Cancer Center, and the University of Arizona comprise the new center based within INBT.

Denis Wirtz—the university’s vice provost for research, INBT’s associate director, professor in the Department of Chemical and Biomolecular Engineering, and a member of the Johns Hopkins Kimmel Cancer Center—will serve as director and principal investigator of the new center.

“Instead of looking at other aspects like tumor growth, I’ll be working with my colleagues in the schools of engineering and medicine to uncover the physical underpinnings of cancer metastasis,” Wirtz said. “The ‘team science’ approach in our center should result in the creation of new therapies targeting metastasis, the primary cause of human cancer deaths.”

wirtz-casual-headshot

Denis Wirtz

Kenneth Pienta, professor of urology, oncology, and pharmacology and molecular sciences at the Johns Hopkins School of Medicine, will serve as the PS-OC’s associate director. Pienta also co-directs Johns Hopkins University inHealth Signature Initiative, a trans-University, and cross-disciplinary effort to coordinate and apply the intelligent use of population health data for individual patients. Currently, his research involves defining tumor microenvironments and how they contribute to the growth of tumors and the spread of cancer. His bench laboratory program is closely tied to the development of novel therapies for prostate cancer.

Ed Schlesinger, dean of the university’s Whiting School of Engineering, endorses Wirtz’s strategy. “By approaching the problem of metastasis from an engineering perspective,” Schlesinger said, “Denis has provided an entirely new understanding of cell motility and has opened the doors to the possibility of new and far more effective cancer treatments.”

This is not the first PS-OC for INBT. Wirtz directed INBT’s first 5-year PS-OC grant, which ran from the fall of 2009 until 2014. This new PS-OC grant creates a brand new center, with projects that have evolved out of the first center’s original research goals. The new center projects include:

  • The Role of Physical Cues in Collective Cell Invasion – This project will examine how the physical forces exerted upon cancer cells when they are confined within a tumor can affect the migration of these cells, both collectively and individually. The team is led by Konstantinos Konstantopoulos, chair of the university’s Department of Chemical and Biomolecular Engineering.
  • Forces Involved in Collective Cell Migration – When they break away from a tumor, some cancer cells seem to prefer to travel in groups. This team, led by center director Wirtz, will study the forces involved in organizing the collective migration of breast cancer cells in both 2D and 3D environments.
  • Impact of low oxygen on the migration of sarcoma cells – Low oxygen within a tumor (hypoxia) dramatically increases pulmonary metastasis and results in poor health outcomes. Researchers led by Sharon Gerecht, a professor of chemical and biomolecular engineering, will try to determine how primary tumor cells respond to oxygen in their microenvironment. The goal is to better understand the spread of cancer and identify new treatment targets.
Dr. Ken Pienta lab coat

Ken Pienta

Other members of the Johns Hopkins PS-OC center include Andy Ewald and Daniele Gilkes of the School of Medicine, Pei-Hsun Wu and Sean X. Sun of the Whiting School of Engineering, Karin Eisinger and Celeste Simon of the University of Pennsylvania, and Charles Wolgemuth of the University of Arizona.

The Hopkins center is part of a nation-wide NCI Physical Sciences-Oncology Network.

“As a complement to traditional cancer research approaches, the innovative trans-disciplinary approaches and perspectives in the PS-ON will aid in unraveling the complexity of cancer,” said Nastaran Kuhn, associate director of NCI’s Division of Cancer Biology PS-ON program. “These approaches are aimed at understanding the mechanistic underpinnings of cancer progression and ultimately developing effective cancer therapies.”

 

 

Drug-chemo combo destroys challenging breast cancer stem cells

Gregg Semenza

Gregg Semenza

Researchers affiliated with Johns Hopkins Physical Sciences-Oncology Center (PS-OC) have shown that combining chemotherapy with an agent that blocks a certain cancer survival protein holds the key to fighting one of the the toughest forms of breast cancer.

Only 20 percent of patients with what are known as “triple-negative” breast cancer cells respond to chemotherapy. PS-OC associate director and Johns Hopkins professor of  medicine Gregg Semenza demonstrated in a recent study that chemotherapy actually enhances triple-negative cancer stem cell survival by switching on proteins called hypoxia-inducible factors (HIF). But when combined with currently available and FDA-approved HIF-inhibiting drugs, such as digoxin, Semenza said, chemotherapy shrank tumors.

Mice with implanted triple-negative breast cancer stem cells were treated with a combination therapy comprised of the HIF-inhibiting drug plus the chemotherapeutic drug paclitaxel. That combo treatment decreased tumor size by 30 percent more than treatment with chemotherapy. Furthermore, Semenza’s study showed that combining digoxin with the a different chemotherapeutic agent called gemcitabine “brought tumor volumes to zero within three weeks and prevented the immediate relapse at the end of treatment that was seen in mice treated with gemcitabine alone,” a press release on the study stated. Clinical trials will be needed to verify these results.

Debangshu Samanta, Ph.D., a postdoctoral fellow in the Semenza lab, was the lead author on this research published online in the Proceedings of the National Academy of Sciences. Additional authors include Daniele Gilkes, Pallavi Chaturvedi and Lisha Xiang of the Johns Hopkins University School of Medicine.

Read the PNAS article here.

Visit the PS-OC website here.

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

 

Veltri presents PS-OC hosted talk on digital pathology and prostate cancer

Robert Veltri, associate professor Of Urology and Oncology at the Johns Hopkins School of Medicine and Director of the Fisher Biomarker Biorepository Laboratory, will  present the talk Quantitative Histomorphometry of Digital Pathology: Case study in prostate cancer,” to members of the Denis Wirtz Lab and the Johns Hopkins Physical Sciences-Oncology Center on Monday, December 9 at 2 p.m. in Croft G40 on the Homewood campus. Seating is limited.

veltri

Robert Veltri

Veltri studies the biomarkers for prostate and bladder cancer and is collaborating on applications of Quantitative Digital Image Analysis (QDIA) using microscopy to quantify nuclear structure and tissue architecture. Collaborations include Case Western Reserve University biomedical engineering and the University of Pittsburgh Electrical Engineering departments studying to assess cancer aggressiveness in prostate cancer (PCa). Furthermore,  he is studying the application of molecular biomarkers for prostate (CaP) and bladder cancer (BlCa) detection and prognosis. Veltri’s work is funded by the National Cancer Institute’s PS-OC program grant), Early Detection Research Network (EDRN), and the Department of Defense related to research on Active Surveillance for PCa. He is also a co-investigator on a SBIR-I and II grant studying the application of microtransponders to multiplex molecular urine and serum biomarker testing for CaP.  Veltri has authored over 152 scientific publications and is either inventor or co-inventor on over twenty patents and two trademarks.

Veltri presents PS-OC hosted talk on digital pathology and prostate cancer

Robert Veltri, associate professor Of Urology and Oncology at the Johns Hopkins School of Medicine and Director of the Fisher Biomarker Biorepository Laboratory, will  present the talk Quantitative Histomorphometry of Digital Pathology: Case study in prostate cancer,” to members of the Denis Wirtz Lab and the Johns Hopkins Physical Sciences-Oncology Center on Monday, December 9 at 2 p.m. in Croft G40 on the Homewood campus. Seating is limited.

veltri

Robert Veltri

Veltri studies the biomarkers for prostate and bladder cancer and is collaborating on applications of Quantitative Digital Image Analysis (QDIA) using microscopy to quantify nuclear structure and tissue architecture. Collaborations include Case Western Reserve University biomedical engineering and the University of Pittsburgh Electrical Engineering departments studying to assess cancer aggressiveness in prostate cancer (PCa). Furthermore,  he is studying the application of molecular biomarkers for prostate (CaP) and bladder cancer (BlCa) detection and prognosis. Veltri’s work is funded by the National Cancer Institute’s PS-OC program grant), Early Detection Research Network (EDRN), and the Department of Defense related to research on Active Surveillance for PCa. He is also a co-investigator on a SBIR-I and II grant studying the application of microtransponders to multiplex molecular urine and serum biomarker testing for CaP.  Veltri has authored over 152 scientific publications and is either inventor or co-inventor on over twenty patents and two trademarks.

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

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 nonmetastatic 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

 

Self-assembling drug molecules could fight cancer

A popular method of targeted drug delivery for anti-cancer drugs involves doping another material with the desired pharmaceutical to obtain better targeting efficiency to tumor sites. The problem with this method, researchers have discovered, is that the quantity of drug payload per delivery unit can vary widely and that the materials used for delivery can have toxic side effects.

But what if you could turn the drug molecule itself into a nanoscale delivery system, cutting out the middleman completely?

TEM image of nanotubes formed by self-assembly of an anticancer drug amphiphile. These nanotubes possess a fixed drug loading of 38% (w/w). Image from Cui Lab.

TEM image of nanotubes formed by self-assembly of an anticancer drug amphiphile. These nanotubes possess a fixed drug loading of 38% (w/w). Image from Cui Lab.

Using the process of molecular self-assembly, that is what Honggang Cui, an assistant professor in the Department of Chemical and Biomolecular Engineering at Johns Hopkins University, is attempting to do. His efforts have netted him the prestigious Faculty Early Career Development (CAREER) Award from the National Science Foundation. Cui, an affiliated faculty member of the Johns Hopkins Institute for NanoBioTechnology, will receive the $500,000 award over five years.

Cui explained that a current method of delivering anti-cancer drugs is to enclose them in a nanoscale carrier made of natural or synthetic materials, but this method presents several challenges. “The amount of drug loaded per carrier is very much limited and varies from batch to batch. Even in the same batch, there is a drug loading variation from carrier to carrier. Additionally, the carrier material itself may have toxic side effects,” he said.

Cui’s research seeks to eliminate the need for the carrier by coaxing the drug molecules themselves to form their own carrier through the process of self-assembly. His team is developing new molecular engineering strategies to assemble anti-cancer drugs into supramolecular nanostructures.

“Such supramolecules could carry as much as 100 percent of the drug, would possess a fixed amount of drug per nanostructure and would minimize the potential toxicity of the carrier,” Cui said.

To learn more about research in the Cui lab go to http://www.jhu.edu/cui/

 

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