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

INBT launches Johns Hopkins Center of Cancer Nanotechnology Excellence

Martin Pomper and Peter Searson will co-direct INBT’s new Center of Cancer Nanotechnology Excellence (Photo: Will Kirk/Homewood-JHU)

Faculty members associated with the Johns Hopkins Institute for NanoBioTechnology have received a $13.6 million five-year grant from the National Cancer Institute to establish a Center of Cancer Nanotechnology Excellence. The new Johns Hopkins center brings together a multidisciplinary team of scientists, engineers and physicians to develop nanotechnology-based diagnostic platforms and therapeutic strategies for comprehensive cancer care. Seventeen faculty members will be involved initially, with pilot projects adding more participants later.

The Johns Hopkins Center of Cancer Nanotechnology Excellence, which is part of the university’s Institute for NanoBioTechnology, is one of several NCI-supported centers launched through a funding opportunity started in 2005. According to the NCI, the program was established to create “multi-institutional hubs that integrate nanotechnology across the cancer research continuum to provide new solutions for the diagnosis and treatment of cancer.”

Peter Searson, who is the Joseph R. and Lynn C. Reynolds Professor of Materials Science and Engineering in the Whiting School of Engineering and director of the Institute for NanoBioTechnology, will serve as the center’s director. The co-director will be Martin Pomper, professor of radiology and oncology at the School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

“A unique feature of the center is the integration of research, education, training and outreach, and technology commercialization,” Searson said.

To move these new technologies toward use by physicians, a Cancer Nanomedicine Commercialization Working Group will be established and headed by John Fini, director of intellectual property for the university’s Homewood campus. This group will be responsible for managing and coordinating the translational process.

Another special feature of the center will be its Validation Core, led by Pomper, who is also associate director of the Johns Hopkins In Vivo Cellular and Molecular Imaging Center and director of the Johns Hopkins Small Animal Imaging Resource Program.

“Validation is about assuring that the experimental products and results we generate are on target and able to measure the biological effects for which they’re intended,” he said.

Searson and Pomper said the center will consist of four primary research projects.

One project will seek methods to screen bodily fluids such as blood or urine for indicators of cancer found outside of the genetic code, indicators called epigenetic markers. Led by Tza-Huei “Jeff” Wang, associate professor of mechanical engineering in the Whiting School of Engineering; Stephen Baylin, the Virginia and Daniel K. Ludwig Professor of Cancer Research in the School of Medicine; and James Herman, a professor of cancer biology in the School of Medicine, this project will use semiconductor nanocrystals, also known as quantum dots, and silica superparamagnetic particles to detect DNA methylation. Methylation adds a chemical group to the exterior of the DNA and is a biomarker frequently associated with cancer.

A second project, led by Anirban Maitra, associate professor of pathology and oncology at the School of Medicine and the Johns Hopkins Kimmel Cancer Center, will focus on curcumin, a substance found in the traditional Indian spice turmeric. In preclinical studies, curcumin has demonstrated anti-cancer properties but, because of its physical size, it is not readily taken up into the bloodstream or into tissues. Engineered curcumin nanoparticles, however, can more easily reach tumors arising in abdominal organs such as the pancreas, Maitra said. This team will try to determine whether nanocurcumin, combined with chemotherapeutic agents, could become a treatment for highly lethal cancers, such as pancreatic cancer.

Hyam Levitsky, professor of oncology at the Johns Hopkins Kimmel Cancer Center, will lead a third project, which will seek to use a noninvasive method to monitor the effectiveness of vaccines for cancer and infectious diseases.

A final project will build on the work of Justin Hanes and Craig Peacock, professors in the School of Medicine, to deliver therapies directly to small cell lung cancer tissue via mucus-penetrating nanoparticles.

All research efforts will be supported by a nanoparticle engineering core, led by Searson, which will make and characterize a variety of nanomaterials. Another core, centering on bioinformatics and data sharing, will be led by Rafael Irizarry, professor of biostatistics at the Johns Hopkins Bloomberg School of Public Health.

Johns Hopkins Institute for NanoBioTechnology

Sidney Kimmel Comprehensive Cancer Center

EOC leader Gregg Semenza wins Canada Gairdner Award

Gregg Semenza

Gregg Semenza, associate director of Johns Hopkins Engineering in Oncology Center (EOC), has been named among seven 2010 winners of Canada’s international prize for medical research–the Canada Gairdner Award. The award is among the most prestigious for medical research and comes with a $100,000 cash prize.

The Canada Gairdner Award recognized Semenza for his work on how cells respond to oxygen availability in the body. He was the first to identify and describe hypoxia-inducible factor-1 (HIF-1), which switches genes on or off in response to oxygen levels.

Semenza leads a research project related to this topic for EOC with Sharon Gerecht, an assistant professor of chemical and biomolecular engineering. Their work focuses on analyzing the makeup and physical properties of the extracellular matrix, the three-dimensional scaffold in which cells live.

“Normal cells live in a flexible scaffold, but cancer cells create a rigid scaffold that they climb through to invade normal tissue,” Semenza said. “We will study how this change occurs and how it is affected by the amount of oxygen to which cancer cells are exposed. Our studies have shown that cancer cells are deprived of oxygen, which incites them to more aggressively invade the surrounding normal tissues where oxygen is more plentiful. Hypoxia-inducible factor 1 controls the responses of cancer cells to low oxygen, and we have recently identified drugs that block the action of HIF-1 and inhibit tumor growth in experimental cancer models.”

Semenza is the C. Michael Armstrong Professor in Medicine and founding director of the Vascular Biology program at  Johns Hopkins Institute for Cell Engineering at the School of Medicine. He also is a member of the McKusick-Nathans Institute of Genetic Medicine, is an affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology, and has ties to the Department of Biological Chemistry and the Sidney Kimmel Comprehensive Cancer Center, both at the Johns Hopkins School of Medicine.

The Johns Hopkins Engineering in Oncology Center, launched October 2009, is one of 12 funded by the National Cancer Institute to bring a new cadre of theoretical physicists, mathematicians, chemists and engineers to the study of cancer. During the five-year initiative, the NCI’s Physical Sciences-Oncology Centers (PS-OC) will take new, nontraditional approaches to cancer research by studying the physical laws and principles of cancer; evolution and evolutionary theory of cancer; information coding, decoding, transfer and translation in cancer; and ways to deconvolute cancer’s complexity.

Read more about Gregg Semenza winning the Canada Gairdner Award in the Johns Hopkins Gazette story by Audrey Huang here.

Johns Hopkins Engineering in Oncology Center

Princeton physicist to discuss physics of cancer cell resistance

Physics professor Robert Austin, right, and graduate ¬student Guillaume Lambert observe prostate cancer cells growing on chips of silicon and silicon-based plastic. (Princeton Office of Communications)

The fact that cancer cells frequently re-emerge after initial therapeutic attempts has dogged the efforts of oncologists to save patients’ lives for decades. According to Princeton physicist, Robert H. Austin, cancer cell resistance is primarily a biological reaction to stress and “one of the great unsolved, and deadly, problems in oncology.”

On Thursday, February 4, Austin will discuss, “The Physics of Cancer,” during a 3 p.m. joint colloquium hosted by Johns Hopkins University departments of Physics and Astronomy and Biophysics in the Schafler auditorium of the Bloomberg Center on the Homewood campus. The talk is free and open to the public.

Austin is principal investigator for Princeton’s Physical Science-Oncology Center and a trans-network partner with Johns Hopkins Engineering in Oncology Center, both of which are National Cancer Institute funded organizations.

Austin will address the general principles of physics, ecology, and biology and why recurrence of resistant cancer cells seems to be a universal phenomenon in cancer. He says that “evolution in small, stressed habitats is key to the rapid and inevitable re-emergence of resistance of cancer cells” (and) “that modern techniques of physical probes, genomics, proteomics and nanotechnology will allow us to analyze the evolutionary path of these emergent resistant cells.”

Related Links

Johns Hopkins Engineering in Oncology Center

Flyer for  Prof. Austin’s colloquium

Physical Sciences in Oncology Centers of the National Cancer Institute