‘Just add water’ to activate freeze-dried brain cancer fighting nanoparticles

A fluorescence micrograph showing brain cancer cells producing a green fluorescent protein. DNA encoded to produce the protein was delivered to the cancer cells by new freeze-dried nanoparticles produced by Johns Hopkins biomedical engineers. Image: Stephany Tzeng/JHU

Biomedical engineers and clinicians at Johns Hopkins University have developed freeze-dried nanoparticles made of a shelf-stable polymer that only need the addition of water to activate their cancer-fighting gene therapy capabilities.

Principal investigator Jordan Green, assistant professor in the department of Biomedical Engineering at the Johns Hopkins School of Medicine, led the team that fabricated the polymer-based particles measuring 80 to 150 nanometers in diameter. Each particle, which is about the size of a virus, has the ability to carry a genetic cocktail designed to produce brain cancer cell-destroying molecules. After manufacture, the nanoparticles can be stored for up to 90 days before use. In principle, cancer therapies based on this technology could lead to a convenient commercial product that clinicians simply activate with water before injection into brain cancer tumor sites.

Because this method avoids the common, unpleasant side effects of traditional chemotherapy, “nanoparticle-based gene therapy has the potential to be both safer and more effective than conventional chemical therapies for the treatment of cancer,” Green said. But, he added current gene therapy nanoparticle preparations are just not practical for clinical use.

“A challenge in the field is that most non-viral gene therapy methods have very low efficacy. Another challenge with biodegradable nanoparticles, like the ones used here is that particle preparation typically takes multiple time-sensitive steps.” Green said. “Delay with formulation results in polymer degradation, and there can be variability between batches. Although this is a simple procedure for lab experiments, a clinician who wishes to use these particles during neurosurgery will face factors that would make the results unpredictable.”

In contrast, the nanoparticles developed by the Green lab are a freeze-dried, or “lyophilized,” formulation. “A clinician would simply add water, and it is ready to inject,” Green said. Green thinks this freeze-dried gene-delivery nanoparticle could be easily manufactured on a large scale.

Co-investigator Alfredo Quinones-Hinojosa, a Johns Hopkins Hospital clinician-scientist and associate professor in the departments of Neurosurgery and Oncology at the Johns Hopkins School of Medicine, said he could imagine particles based on this technology being used in conjunction with, and even instead of, brain surgery. “I envision that one day, as we understand the etiology and progression of brain cancer, we will be able to use these nanoparticles even before doing surgery,” Quinones said. “How nice would that be? Imagine avoiding brain surgery all together!”

Currently, patients with glioblastoma, or brain cancer, only have a median survival of about 14 months, Green said. “Methods other than the traditional chemotherapy drugs and radiation—or in combination with them—may improve prognosis,” he said.

Gene therapy approaches could also be personalized, Green said. “Because gene therapy can take advantage of many naturally-existing pathways and can be targeted to the cancer type of choice through nanoparticle design and transcriptional control, several levels of treatment specificity could be provided,” Green said.

The nanoparticles self-assemble from a polymer structural unit, so fabrication is fairly simple, said Green. Finding the right polymer to use, however, proved to be a challenge. Lead author Stephany Tzeng, a PhD student in biomedical engineering in Green’s lab screened an assortment of formulations from a “polymer library” before hitting on a winning combination.

“One challenge with a polymer library approach is that there are many polymers to be synthesized and nanoparticle formulations to be tested. Another challenge is designing the experiments to find out why the lead formulation works so well compared to other similar polymers and to commercially available reagents,” Green said.

Tzeng settled on a particular formulation of poly(beta-amino ester)s specifically attracted to glioblastoma (GB) cells and to brain tumor stem cells (BTSC), the cells responsible for tumor growth and spread. “Poly(beta-amino ester) nanoparticles are generally able to transfect many types of cells, but some are more specific to GBs and BTSCs,” Tzeng said.

The nanoparticles work like a virus, co-opting the cell’s own protein-making machinery, but in this case, to produce a reporter gene (used to delineate a tumor’s location) or new cancer fighting molecule. “It is possible that glioblastoma-derived cells, especially brain tumor stem cells, are more susceptible to our gene delivery approach because they divide much faster,” Tzeng added.

Not only are the particles convenient to use, the team discovered that dividing cells continued to make the new protein for as long as six weeks after application. “The gene expression peaked within a few days, which would correspond to a large initial dose of a therapeutic protein,” said Green. “The fact that gene expression can continue at a low level for a long time following injection could potentially cause a sustained, local delivery of the therapeutic protein without requiring subsequent injection or administration. The cells themselves would act as a ‘factory’ for the drug.”

Once the nanoparticles release their DNA cargo, Tzeng said the polymer quickly degrades in water, usually within days. “From there, we believe the degradation products are processed and excreted with other cellular waste products,” Tzeng said.

Members of the Green Lab are now working on identifying the intracellular mechanism responsible for facilitating cell-specific delivery. “We also plan to build additional levels of targeting into this system to make it even more specific. This includes modifying the nanoparticles with ligands to specifically bind to glioblastoma cells, making the DNA cargo able to be expressed only in GB cells, and using a DNA sequence whose product is only effective in GB cells.”

So far, the team has only successfully transfected brain tumor stem cells using these nanoparticles in a plastic dish. The next step is to test the particle in animal models.

“We hope to begin tests in vivo in the near future by implanting brain tumor stem cells into a mouse and injecting particles. We also hope to begin using functional genes that would kill cancer cells in addition to the fluorescent proteins that serve only as a marker,” Tzeng said.

Other authors who contributed to this work are Hugo Guerrero-Cázares, postdoctoral fellow in Neurosurgery and Oncology, and Joel Sunshine, an M.D.-Ph.D. candidate, and Elliott Martinez, an undergraduate leadership alliance summer student, both from Biomedical Engineering. Funding for this work came from the National Institutes of Health, Howard Hughes Medical Institute, the Robert Wood Johnson Foundation and a pilot-grant from Johns Hopkins Institute for NanoBioTechnology (INBT). Green is an affiliated faculty member of INBT. The research will be published in Issue #23 (August 2011) of the journal Biomaterials and is currently available online.

Freeze-dried gene therapy system avoids virus, complications

Story by Mary Spiro

 

Hopkins alumni learn about engineering in oncology

Denis Wirtz directs INBT’s Engineering in Oncology Center. Photo: Mary Spiro

As  part of Johns Hopkins Alumni Weekend 2011, Denis Wirtz, director of the Johns Hopkins Engineering in Oncology Center, gave a talk April 29 on how researchers are using physics and engineering to better understand cancer. Wirtz is the Theophilus H. Smoot Professor in the Whiting School of Engineering Department of Chemical and Biomolecular Engineering.

Wirtz spoke in Mason Hall Auditorium with about 100 alumni in attendance. He showed animations explaining the process of metastasis and concluded his remark with a viewing of the short movie “INBT: An Overview.” The audience seemed engaged and asked several questions following Wirtz’s presentation. The talk was presented for the Class of ’61 alumni.

Johns Hopkins Engineering in Oncology Center is a Physical Sciences-Oncology Center funded by the National Cancer Institute. It was established in 2009.

To see the full gallery of photos from this event, visit this link on the PS-OC  Facebook page.

Johns Hopkins Cancer Nanotechnology Training Center (CNTC) launched

(Photo: Mary Spiro/INBT)

The war on cancer is fought on many fronts, even tiny, nanoscale ones. To train new scientists and engineers to combat the spread of cancer, Johns Hopkins Institute for NanoBioTechnology (INBT) has established a pre-doctoral (PhD) training program in Nanotechnology for Cancer Medicine. Together with the institute’s previously established Nanotechnology for Cancer Medicine postdoctoral fellowship, these two training programs will comprise the Johns Hopkins Cancer Nanotechnology Training Center (CNTC).

Similar to the postdoctoral program, the PhD training in nanotechnology for cancer medicine will educate graduate students to use nanotechnology solutions to diagnose, treat, manage, and hopefully one day, even cure cancer, said the CNTC’s director Denis Wirtz, the Theophilus H. Smoot professor of Chemical and Biomolecular Engineering in the Whiting School of Engineering.

The CNTC was funded by a $1.8 million grant over five years from the National Cancer Institute. Launched in the fall of 2010, the pre-doctoral training program has already attracted highly qualified students with bachelor’s degrees in diverse backgrounds such as biochemistry, genetics, molecular and cellular biology, as well as those who majored in engineering or physics. By attracting students with these sorts of educational backgrounds, Wirtz said, INBT will help develop what he calls “hybrid scientists, engineers, and clinicians.”

“We are seeking to train people who can develop new nanoscale materials and nanoparticles that will address biological functions related to the growth and spread of cancer, or metastasis, at a mechanistic level,” said Wirtz, who also directs INBT’s Engineering in Oncology Center and is INBT’s associate director.

Anirban Maitra, professor of pathology and oncology at the Johns Hopkins School of Medicine and co-director of the CNTC, said research will focus on the identification and preclinical validation of the most cancer-specific nanotechnology based therapies, particularly using the wealth of knowledge on the cancer genome emerging from CNTC participant scientists such as Kenneth Kinzler and Bert Vogelstein, both School of Medicine faculty.

“The CNTC is uniquely poised to leverage this information for developing molecularly targeted nanotechnology-based tools for cancer therapy,” Maitra added.

Much like INBT’s other training programs, students seeking a doctorate specialization in nanotechnology for cancer medicine must jump through a few additional hoops than those students enrolled in traditional department-based pre-doctoral programs.

For example, in addition to the PhD requirements set forth by students’ home departments, CNTC fellows also complete two core nanotechnology courses, two intensive laboratory “boot camps”, one laboratory course designed to develop their skills in experimental and theoretical fundamentals in surface and materials science for biology and medicine, and one course in advanced cancer biology. Students must also complete two complementary laboratory rotations within their first year, participate in a professional development seminars, attend clinical conferences on cancer, among many other requirements. These extra steps set INBT trainees apart by giving them a more advanced skill set and making graduates more desirable in the job market, Wirtz said.

Generally, fellows take five to six years to complete the cancer nanotechnology for medicine PhD program. INBT will support CNTC trainees for two years, after which, the students will be funded by their primary departments from which their degrees will be conferred.

As many as six outstanding pre-doctoral fellows may enter the CNTC program per year. Candidates from under-represented groups in the science and engineering disciplines, including women and minorities, are encouraged to apply.

For more information about how to apply for the CNTC programs, please contact INBT’s Academic Program Administrator, Ashanti Edwards, at Ashanti@jhu.edu.

Johns Hopkins Physical Sciences-Oncology Center

Center of Cancer Nanotechnology Excellence

Story by Mary Spiro

 

Agenda, workshops set for Johns Hopkins cancer nanotech symposium

Hands-on workshops are part of this year’s INBT symposium. (Photo: Marty Katz/baltimorephotographer.com)

Cancer Nanotechnology forms  the focus of the fifth annual symposium for Johns Hopkins Institute for NanoBioTechnology (INBT), May 12 and 13, 2011 at the university’s Homewood campus. Friday, May 13 will feature a symposium with talks from a slate of faculty experts in nanotechnology, oncology, engineering and medicine, while hands-on workshops will be offered to small groups on Thursday, May 12.

Registration begins at 8:30 a.m. in Shriver Hall Auditorium. A poster session begins at 1:30 p.m. upstairs in the Clipper Room showcasing research from INBT affiliated faculty laboratories across several Johns Hopkins University divisions. Past symposiums have attracted as many as 500 attendees and more than 100 research posters. To register and to submit a poster, click here.

Agenda

Cancer Nanotechnology: The annual symposium of Johns Hopkins Institute for NanoBioTechnology

May 13, 2011, Shriver Hall

8:30-9:00 am: Registration, Lobby of Shriver Hall

9:00-9:05 am: Welcome/Introduction of Speakers, Denis Wirtz

9:05-9:35 am: “Why develop sensitive detection systems for abnormal DNA methylation in cancer?”

Stephen Baylin is Deputy Director, Professor of Oncology and Medicine, Chief of the Cancer Biology Division and Director for Research of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

9:35-9:55 am: “Enabling cancer drug delivery using nanoparticles”

Anirban Maitra is a professor at Johns Hopkins School of Medicine with appointments in Pathology and Oncology at the Sol Goldman Pancreatic Research Center and secondary appointments in Chemical and Biomolecular Engineering at the Whiting School of Engineering and the McKusick-Nathans Institute of Genetic Medicine. Maitra co-directs Johns Hopkins Cancer Nanotechnology Training Center and is a project director in the CCNE.

9:55-10:15 am: “Epithelial Morphogenesis in Cancer Metastasis”

Gregory Longmore is a professor at the Washington University in St. Louis School of Medicine, Department of Medicine, Oncology Division, Molecular Oncology Section and the Department of Cell Biology and Physiology. Longmore is a project co-director at Johns Hopkins Physical Sciences-Oncology Center (PS-OC).

10:15-10:35 am: “A Translational Nanoparticle-Based Imaging Method for Cancer”

Martin Pomper is a professor at Johns Hopkins School of Medicine with a primary appointment in Radiology and secondary appointments in Oncology, Radiation Oncology, and Pharmacology and Molecular Sciences, as well as Environmental Health Sciences at the Johns Hopkins Bloomberg School of Public Health. Pomper co-directs Johns Hopkins Center of Cancer Nanotechnology Excellence (CCNE)

10:35-10:50 am: Break

10:50-10:55 am: Welcome/Introduction of Speakers, Anirban Maitra

10:55-11:15 am: “Cancer Cell Motility in 3-D”

Denis Wirtz is the Theophilus H. Smoot Professor of Chemical and Biomolecular Engineering in the Whiting School of Engineering at Johns Hopkins University. Wirtz is associate director of INBT and director of the Johns Hopkins Physical Sciences-Oncology Center, also known as the Engineering in Oncology Center. He has a secondary appointment in Oncology at the Johns Hopkins School of Medicine.

11:15-11:35 am: “MRI as a Tool for Developing Vaccine Adjuvants”

Hy Levitsky is a professor of Oncology, Medicine and Urology at the Johns Hopkins School of Medicine and the Scientific Director of the George Santos Bone Marrow Transplant Program. Levitsky is a project director at the Center of Cancer Nanotechnology Excellence (CCNE).

11:35-11:55 am: “Genetically Encodable FRET-based Biosensors for probing signaling dynamics”

Jin Zhang is an associate professor at Solomon H. Snyder Department of Neuroscience at Johns Hopkins School of Medicine with primary appointments in Pharmacology and Molecular Sciences and secondary appointments in Neuroscience, Oncology, and Chemical and Biomolecular Engineering.

11:55-12:00 pm: Adjourn/Concluding Remarks, Thomas Fekete, director of corporate partnerships, INBT

12:00-1:30 pm: Break

1:30-3:30 pm: Research Poster Session, Clipper Room, Shriver Hall

Workshops give hands-on experience to nano-bio researchers

In conjunction with the fifth annual symposium talks and poster session, Johns Hopkins Institute for NanoBioTechnology will hold hands-on laboratory workshops to introduce some of the methods developed by affiliated faculty. Space is limited to participate in the workshops, which will be held the afternoon of May 12 at INBT’s headquarters in Suite 100 of the New Engineering Building. Times, instructors and topics are listed below. If you are interested in signing up for one or more of the workshops, please contact INBT’s administrative coordinator Tracy Smith at TracyINBT@jhu.edu or call 410-516-5634.

For more information about INBT’s symposium go to: http://inbt.jhu.edu/outreach/symposium/twentyeleven/

Session A: 1-3 pm

1. Electrospinning of polymeric nanofibers for tissue engineering application: Nanofibrous materials are increasingly used in tissue engineering and regenerative medicine applications and for local delivery of therapeutic agents. Electrospinning is the most widely used method for producing nanofiber matrices because of its high versatility and capacity to generate nanofibers from a variety of polymer solutions or melts. It can generate fibers with diameters ranging from tens of nanometers to a few microns. This workshop will review the basic principle of electrospinning, investigate the effect of several key parameters on fiber generation, demonstrate the method to generate nanofiber mesh and nanofiber conduits, and discuss the potential applications for tissue engineering and repair.

Instructors: Russell Martin and Hai-Quan Mao (Mao Lab)

2. Particle tracking microrheology: This hands-on course will teach participants the fundamentals and applications of high-throughput approaches to cytometry, including cell morphometry and microrheology. These approaches are being used for rapid phenotyping of cancer cells.

Instructors: Wei-Chiang Chen, Pei-Hsun Wu, and Denis Wirtz (Wirtz Lab)

Session B: 3:30-5:30 pm

3. Synthesis of quantum dots for bioengineering: This workshop will provide a hands-on approach to the synthesis of CdSe QD cores and how to purify these cores from excess surfactant. A brief discussion how to successfully electrically passivate the cores will follow. Participants will be able to water solubilize core/shell QDs using pegylated lipids. Several methods for characterizing the QDs through the synthesis and water solubilization will be performed.

Instructors: Charli Dvoracek, Justin Galloway, and Jeaho Park (Searson Lab)

4. Microfluidics for studying cell adhesion: This workshop will focus on fabrication of an “artificial blood vessel” via photolithography to generate a micron-sized (cross-section) channel. The micro-channel will be connected to a syringe pump to initiate fluid flow simulating the blood flow inside a blood vessel. This tool can be used to study how cancer cells interact with “blood vessel” surface when coated with adhesion proteins.

Instructors: Tommy Tong and Eric Balzer (K. Konstantopoulos Lab)

Story by Mary Spiro

 

Cancer nanotechnology mini-symposium brings students together

Jeaho Park, predoctoral student affiliated with the CCNE,  presenting at the INBT mini-symposium on cancer nanotechnology. (Photo: Mary Spiro)

About 30 people attended a mini-symposium on cancer nanotechnology hosted by Johns Hopkins Institute for NanoBioTechnology March 23. The event showcased current research from nine students affiliated with its Physical Sciences-Oncology Center (PS-OC) and Center of Cancer Nanotechnology Excellence (CCNE). Talks began at 9 a.m. in Hackerman Hall Auditorium.

“We become so focused on our own research that we don’t know what other students are working on,” said Stephanie Fraley, a predoctoral candidate chemical and biomolecular engineering in the laboratory of Denis Wirtz. “The beauty of an event like this is that we get to see work from across the campuses and across disciplines, all in one morning.”

Researchers, who each spoke for 15 minutes and fielded questions from the audience,  included the following:

  • 9:00 – 9:15 – Jeaho Park (Peter Searson Lab, CCNE): Quantum dots for targeting cancer biomarkers
  • 9:15 – 9:30 – Stephanie Fraley (Denis Wirtz Lab, PSOC): Role of Dimensionality in Focal Adhesion Protein Localization and Function
  • 9:15 – 9:30 – Kelvin Liu, PhD, (Jeff Wang Lab, CCNE): Decoding Circulating Nucleic Acids in Serum Using Microfluidic Single Molecule Spectroscopy
  • 9:45 – 10:00 – Laura Dickinson (Sharon Gerecht Lab, PSOC): Functional surfaces to investigate cancer cell interactions with hyaluronic acid
  • 10:00 – 10:15 – Craig Schneider (Justin Hanes Lab, CCNE): Mucus-penetrating particles for the treatment of lung cancer
  • Break
  • 11:00 – 11:15 – Eric Balzer, PhD, (K. Konstantopoulos Lab, PSOC): Migrating tumor cells dynamically adapt to changes in environmental geometry
  • 11:15 – 11:30 – Venugopal Chenna (Anirban Maitra Lab, CCNE): Systemic Delivery of Polymeric Nanoparticle Encapsulated Small Molecule Inhibitors of Hedgehog Signaling Pathway for the Cancer therapy
  • 11:30 – 11:45 – Sam Walcott, PhD, (Sean Sun Lab, PSOC): Surface stiffness influences focal adhesion nucleation and decay initiation, but not growth or decay
  • 11:45 – 12:00 – Yi Zhang (Jeff Wang Lab, CCNE): A quantum dot enabled ultrahigh resolution analysis of gene copy number variation

Download the CCNE-PSOC mini symposium agenda here.

John Fini, director of intellectual property for the Homewood campus schools, also gave a presentation on intellectual property and work of Johns Hopkins Technology Transfer.  Plans are in the works for the cancer nanotechnology min-symposiums to occur each spring and fall.

Johns Hopkins Physical Sciences-Oncology Center (PS-OC), also known as the Engineering in Oncology Center, is funded by a grant from the National Cancer Institute and aims to unravel the physical underpinnings involved in the growth and spread of cancer. Johns Hopkins Center of Cancer Nanotechnology Excellence, also funded by a grant from the NCI, aims to use a multidisciplinary approach to develop nanotechnology-based tools and strategies for comprehensive cancer diagnosis and therapy and to translate those tools to the marketplace.

Sponsors needed for JHU nano-bio symposium

Andrew Wong and Noah Tremblay peruse the first issue of NanoBio Magazine (Photo by Charli Dvoracek/INBT)

Cancer Nanotechnology is the theme of the fifth annual symposium of Johns Hopkins Institute for NanoBioTechnology (INBT), May 12-13, 2011 at the university’s Homewood campus. Sponsors are needed to help offset the cost of publishing Nano-Bio magazine, which serves as the event’s program and to provide prizes for top poster presenters. The poster session will feature at least 80 research posters from INBT affiliated research laboratories.

If you or your organization would like to learn how to sponsor the INBT’s annual symposium, please contact our director of corporate partnerships, Tom Fekete, at tmfeke@jhu.edu or call him at 410-516-8891. Sponsors enjoy reduced rates on symposium-related events and advertising in our annual Nano-Bio magazine/symposium program, among other benefits.

Additionally, INBT also needs sponsors to donate prizes for the poster session. Books, gift cards, science-themed t-shirts and the like all make wonderful prizes for our student researchers. If your organization would like to donate a prize, please contact INBT’s science writer Mary Spiro at mspiro@jhu.edu or 410-516-4802.

For more details on the symposium, including a list of speakers, click here or go to http://inbt.jhu.edu/outreach/symposium/twentyeleven/

To learn more about sponsorship, click here or go to http://inbt.jhu.edu/outreach/symposium/twentyeleven/sponsorship-information/

Mini symposium highlights Johns Hopkins student work in cancer nanotechnology

Maureen Wanjara and Laura Dickinson, Johns Hopkins INBT predoctoral students from Sharon Gerecht’s lab (Photo: Marty Katz)

Johns Hopkins Institute for NanoBioTechnology will host a half-day mini-symposium on Wednesday, March 23 to showcase current research from students affiliated with its Engineering in Oncology Center and Center of Cancer Nanotechnology Excellence. Talks begin at 9 a.m. in Hackerman Hall Auditorium (Room B17) and will conclude by noon.

Students speaking include from the Whiting School of Engineering, predoctoral fellows in Chemical and Biomolecular Engineering Stephanie Fraley, Laura Dickinson, and Craig Schneider; and postdoctoral fellows Christopher Hale, Jaeho Park, and Eric Balzer. Speaking from Biomedical Engineering will be predoctoral fellow Yi Zhang and undergradute Kelvin Liu; and in Mechanical Engineering postdoctoral fellow Sam Walcott. Also giving presentations are predoctoral fellow Dipankar Pramanik in Pathology at the Johns Hopkins School of Medicine and John Fini, director of intellectual property for the Homewood campus schools.

Johns Hopkins Engineering in Oncology Center, a Physical Sciences-Oncology Center (PS-OC) funded by a grant from the National Cancer Institute, aims to unravel the physical underpinnings involved in the growth and spread of cancer. Johns Hopkins Center of Cancer Nanotechnology Excellence, also funded by a grant from the NCI, aims to use a multidisciplinary approach to develop nanotechnology-based tools and strategies for comprehensive cancer diagnosis and therapy and to translate those tools to the marketplace.

There is no need to RSVP for the mini-symposium. All Johns Hopkins students, faculty and staff are welcome to attend.

John Hopkins Institute for NanoBioTechnology

Engineering in Oncology Center

Center of Cancer Nanotechnology Excellence

Cancer Nanotechnology theme of INBT’s symposium, May 12-13

The Denis Wirtz lab research centers on investigations of cell micromechanics, cell architecture, nuclear shape and gene expression. Shown are healthy mouse cells with flurorescent staining of the nucleus (blue) and microtubules (green) emanating from the microtubule organizing center (red). (Photo: Wirtz Lab/JHU)

Nanoscale tools developed by engineers have yet to be fully explored and exploited for the diagnosis and treatment of diseases such as cancer. Nanotechnology for Cancer Medicine forms the focus of the fifth annual symposium for Johns Hopkins Institute for NanoBioTechnology (INBT), May 12 and 13, 2011 at the university’s Homewood campus.

Friday, May 13 will feature a symposium with talks from a slate of faculty experts in nanotechnology, oncology, engineering and medicine. Registration begins at 8:30 a.m. in Shriver Hall Auditorium.  A poster session begins at 1:30 p.m. upstairs in the Clipper Room showcasing research from INBT affiliated faculty laboratories across several Johns Hopkins University divisions. Past symposiums have attracted as many as 500 attendees and more than 100 research posters.

Keep checking INBT’s 2011 symposium page for updated information on speakers and more details on how to register and submit a poster title. The symposium and poster session are free for Johns Hopkins affiliated faculty, staff and students.

Keynote Speaker

Stephen B. Baylin is currently Deputy Director, Professor of Oncology and Medicine, Chief of the Cancer Biology Division and Director for Research, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.For the last 20 years, Stephen Baylin has studied the role of epigenetic gene silencing in the initiation and progression of human cancer. He and his colleagues have fostered the concept that DNA hypermethylation of gene promoters, and associated transcriptional silencing, can serve as an alternative to mutations for producing loss of tumor suppressor gene function. They have described some of the classic genes involved, invented approaches to randomly screen the cancer genome for such genes and to demonstrate their functional role in cancer progression, helped begin unravel the molecular mechanisms responsible for the initiation and maintenance of the gene silencing, and worked to utilize all of their findings for translational purposes.  Baylin has authored or co-authored over 375 full-length publications on the above and other areas of cancer biology.

Stephen Baylin will present the keynote talk at the 2011 Johns Hopkins Nano-Bio Symposium

He has been a member of committees of the American Cancer Society and of National Institutes of Health, and his honors include a Research Career Development Award from NIH, the Edwin Astwood Lectureship of the Endocrine Society, the 2003 Jack Shultz Memorial Lecture in Genetics, Fox Chase  Cancer Center, The 2004 National Investigator of the Year Award from the National Cancer Institute SPORE program, the Jack Gibson Visiting Professorship, University of Hong Kong Queen Mary Hospital, Hong Kong, The 2004 2nd Annual Sydney E. Salmon Lectureship in Translational Research, Arizona Cancer Center, the 2005 Shubitz Cancer Research Prize from the University of Chicago, and he currently holds the Virginia and D.K. Ludwig Chair in Cancer Research at Johns Hopkins. Baylin is also recipient of the 2007 Woodward Visiting Professor, Memorial Sloan-Kettering Cancer Center, the 2008 Raffaele Tecce Memorial Lecture, Trento, Italy, the 2008 The David Workman Memorial Award (jointly with Peter A. Jones, Ph.D.) from the Samuel Waxman Foundation, and the 2009 Kirk A. Landon-AACR Prize for Basic Cancer Research, also shared with Peter A. Jones, the 14th NCI Alfred G. Knudson Award in Cancer Genetics, and, most recently, the Nakahara Memorial Lecture prize at the 2010 Princess Takematsu  Symposium. Currently, he leads, with Peter Jones, the Epigenetic Therapy Stand up to Cancer Team.

Additional confirmed speakers for the 2011 INBT Symposium include:

  • Martin Pomper is a professor at Johns Hopkins School of Medicine with a primary appointment in Radiology and secondary appointments in Oncology, Radiation Oncology, and Pharmacology and Molecular Sciences, as well as Environmental Health Sciences at the Johns Hopkins Bloomberg School of Public Health. Pomper co-directs Johns Hopkins Center of Cancer Nanotechnology Excellence (CCNE).
  • Anirban Maitra is a professor at Johns Hopkins School of Medicine with appointments in Pathology and Oncology at Sol Goldman Pancreatic Research Center and secondary appointments in Chemical and Biomolecular Engineering at the Whiting School of Engineering and the McKusick-Nathans Institute of Genetic Medicine. Maitra co-directs Johns Hopkins Cancer Nanotechnology Training Center and is a project director in the CCNE.
  • Jin Zhang is an associate professor at Solomon H. Snyder Department of Neuroscience at Johns Hopkins School of Medicine with primary appointments in Pharmacology and Molecular Sciences and secondary appointments in Neuroscience, Oncology, and Chemical and Biomolecular Engineering.
  • Hy Levitsky is a professor of Oncology, Medicine and Urology at the Johns Hopkins School of Medicine and the Scientific Director of the George Santos Bone Marrow Transplant Program. Levitsky is a project director at the Center of Cancer Nanotechnology Excellence (CCNE).
  • Gregory Longmore is a professor at the Washington University in St. Louis School of Medicine, Department of Medicine, Oncology Division, Molecular Oncology Section and the Department of Cell Biology and Physiology. Longmore is a project co-director at Johns Hopkins Physical Sciences-Oncology Center (PS-OC).
  • Denis Wirtz is the Theophilus H. Smoot Professor of Chemical and Biomolecular Engineering in the Whiting School of Engineering at Johns Hopkins University. Wirtz is associate director of INBT and director of the Johns Hopkins Physical Sciences-Oncology Center, also known as the Engineering in Oncology Center. He has a secondary appointment in Oncology at the Johns Hopkins School of Medicine.

Workshops

During the afternoon of May 12, INBT will hold four 2-hour hands-on laboratory workshops organized by faculty affiliated with INBT, PS-OC or CCNE. Workshop registration will be limited to 10 persons per session. Sessions will begin at 1 and 3:30 p.m. and will be held in the New Engineering Building. Workshop details, including any costs, are forthcoming.

Become a sponsor

If you or your organization would like to learn how to sponsor INBT’s annual symposium, please contact our director of corporate partnerships, Tom Fekete, at tmfeke@jhu.edu or call him at 410-516-8891. Sponsors enjoy reduced rates on symposium-related events and advertising in our annual Nano-Bio magazine/symposium program, among other benefits.

Media inquiries may be directed to Mary Spiro, science writer and media relations director for INBT, at mspiro@jhu.edu or 410-516-4802.

Platelets, coagulation and cancer metastasis: a sticky situation in the blood

Owen McCarty

Join the Chemical and Biomolecular Engineering department for the first seminar of 2011: “Platelets, Coagulation and Cancer Metastasis: a Sticky Situation in the Blood” at 10:45 a.m., Thursday, March 3 in room 301 of Shaffer Hall at the Homewood campus of Johns Hopkins University. Owen J.T. McCarty of Oregon Health and Science University is the invited speaker.

McCarty serves as an assistant professor at OHSU in Portland in the departments of Biomedical Engineering and Cell and Developmental biology. He studies the interplay between cell biology and fluid mechanics in the cardiovascular system. His investigation into the balance between hydrodynamic shear forces and chemical adhesive interactions could shed light on the underlying processes of cancer, cardiovascular disease, and inflammation.

An alumnus of Johns Hopkins University, McCarty’s 2002 Ph.D. dissertation in Chemical and Biomolecular Engineering focused on the role of platelets in cancer metastasis and thrombosis. At the Department of Pharmacology, Oxford University and Centre for Cardiovascular Sciences, University of Birmingham, UK, he continued his research as a Wellcome Trust Postdoctoral Fellow in the area of thrombosis, examining the signaling pathways that rule platelet cytoskeletal reorganization. McCarty’s talk is co-sponsored by the Johns Hopkins Physical Sciences Oncology Center.

Johns Hopkins Physical Sciences Oncology Center

Cells studied in 3-D may reveal novel cancer targets

Stephanie Fraley

Stephanie Fraley, a doctoral student in chemical and biomolecular engineering, was lead author of the study. Photo by Will Kirk/HomewoodPhoto.jhu.edu

Showing movies in 3-D has produced a box-office bonanza in recent months. Could viewing cell behavior in three dimensions lead to important advances in cancer research? A new study led by Johns Hopkins University engineers indicates it may happen. Looking at cells in 3-D, the team members concluded, yields more accurate information that could help develop drugs to prevent cancer’s spread.

“Finding out how cells move and stick to surfaces is critical to our understanding of cancer and other diseases. But most of what we know about these behaviors has been learned in the 2-D environment of Petri dishes,” said Denis Wirtz, director of the Johns Hopkins Engineering in Oncology Center and principal investigator of the study. “Our study demonstrates for the first time that the way cells move inside a three-dimensional environment, such as the human body, is fundamentally different from the behavior we’ve seen in conventional flat lab dishes. It’s both qualitatively and quantitatively different.”

One implication of this discovery is that the results produced by a common high-speed method of screening drugs to prevent cell migration on flat substrates are, at best, misleading, said Wirtz, who also is the Theophilus H. Smoot Professor of Chemical and Biomolecular Engineering at Johns Hopkins. This is important because cell movement is related to the spread of cancer, Wirtz said. “Our study identified possible targets to dramatically slow down cell invasion in a three-dimensional matrix.”

When cells are grown in two dimensions, Wirtz said, certain proteins help to form long-lived attachments called focal adhesions on surfaces. Under these 2-D conditions, these adhesions can last several seconds to several minutes. The cell also develops a broad, fan-shaped protrusion called a lamella along its leading edges, which helps move it forward. “In 3-D, the shape is completely different,” Wirtz said. “It is more spindlelike with two pointed protrusions at opposite ends. Focal adhesions, if they exist at all, are so tiny and so short-lived they cannot be resolved with microscopy.”

The study’s lead author, Stephanie Fraley, a Johns Hopkins doctoral student in Chemical and Biomolecular Engineering, said that the shape and mode of movement for cells in 2-D are merely an “artifact of their environment,” which could produce misleading results when testing the effect of different drugs. “It is much more difficult to do 3-D cell culture than it is to do 2-D cell culture,” Fraley said. “Typically, any kind of drug study that you do is conducted in 2D cell cultures before it is carried over into animal models. Sometimes, drug study results don’t resemble the outcomes of clinical studies. This may be one of the keys to understanding why things don’t always match up.”

collagen fibers

Reflection confocal micrograph of collagen fibers of a 3D matrix with cancer cells embedded. Image by Stephanie Fraley/Wirtz Lab

Fraley’s faculty supervisor, Wirtz, suggested that part of the reason for the disconnect could be that even in studies that are called 3-D, the top of the cells are still located above the matrix. “Most of the work has been for cells only partially embedded in a matrix, which we call 2.5-D,” he said. “Our paper shows the fundamental difference between 3-D and 2.5-D: Focal adhesions disappear, and the role of focal adhesion proteins in regulating cell motility becomes different.”

Wirtz added that “because loss of adhesion and enhanced cell movement are hallmarks of cancer,” his team’s findings should radically alter the way cells are cultured for drug studies. For example, the team found that in a 3-D environment, cells possessing the protein zyxin would move in a random way, exploring their local environment. But when the gene for zyxin was disabled, the cells traveled in a rapid and persistent, almost one-dimensional pathway far from their place of origin.

Fraley said such cells might even travel back down the same pathways they had already explored. “It turns out that zyxin is misregulated in many cancers,” Fraley said. Therefore, she added, an understanding of the function of proteins like zyxin in a 3-D cell culture is critical to understanding how cancer spreads, or metastasizes. “Of course tumor growth is important, but what kills most cancer patients is metastasis,” she said.

To study cells in 3-D, the team coated a glass slide with layers of collagen-enriched gel several millimeters thick. Collagen, the most abundant protein in the body, forms a network in the gel of cross-linked fibers similar to the natural extracellular matrix scaffold upon which cells grow in the body. The researchers then mixed cells into the gel before it set. Next, they used an inverted confocal microscope to view from below the cells traveling within the gel matrix. The displacement of tiny beads embedded in the gel was used to show movement of the collagen fibers as the cells extended protrusions in both directions and then pulled inward before releasing one fiber and propelling themselves forward.

Fraley compared the movement of the cells to a person trying to maneuver through an obstacle course crisscrossed with bungee cords. “Cells move by extending one protrusion forward and another backward, contracting inward, and then releasing one of the contacts before releasing the other,” she said. Ultimately, the cell moves in the direction of the contact released last.

When a cell moves along on a 2-D surface, the underside of the cell is in constant contact with a surface, where it can form many large and long-lasting focal adhesions. Cells moving in 3-D environments, however, only make brief contacts with the network of collagen fibers surrounding them–contacts too small to see and too short-lived to even measure, the researchers observed.

“We think the same focal adhesion proteins identified in 2-D situations play a role in 3-D motility, but their role in 3-D is completely different and unknown,” Wirtz said. “There is more we need to discover.”

Fraley said her future research will be focused specifically on the role of mechanosensory proteins like zyxin on motility, as well as how factors such as gel matrix pore size and stiffness affect cell migration in 3-D.

Co-investigators on this research from Washington University in St. Louis were Gregory D. Longmore, a professor of medicine, and his postdoctoral fellow Yunfeng Feng, both of whom are affiliated with the university’s BRIGHT Institute. Longmore and Wirtz lead one of three core projects that are the focus of the Johns Hopkins Engineering in Oncology Center, a National Cancer Institute-funded Physical Sciences in Oncology Center. Additional Johns Hopkins authors, all from the Department of Chemical and Biomolecular Engineering, were Alfredo Celedon, a recent doctoral recipient; Ranjini Krishnamurthy, a recent bachelor’s degree recipient; and Dong-Hwee Kim, a current doctoral student.

Funding for the research was provided by the National Cancer Institute.  This study, a collaboration with researchers at Washington University in St. Louis, appeared in the June issue of Nature Cell Biology.

Related links:

Johns Hopkins Engineering in Oncology Center

Department of Chemical and Biomolecular Engineering

Watch a related video on YouTube

Story by Mary Spiro