Save the date: fall mini-symposium set for Oct. 24

Graduate students and post doctoral fellows from the Johns Hopkins Institute for NanoBioTechnology, Center of Cancer Nanotechnology Excellence and Physical Science-Oncology Center will host a mini-symposium highlighting some of the current investigations occurring in these research entities. The symposium will include short talks from six to eight researchers and will be held on Wednesday, Oct. 24 from 9 a.m. to noon at a Homewood campus location to be determined. Check back for location and agenda.

View the agendas from previous INBT/CCNE/PSOC mini-symposiums  at the links below:

Spring 2012

Fall 2011

Spring 2011

Killing prostate cancer cells with out harming the healthy cells

Experimenting with human prostate cancer cells and mice, cancer imaging experts at Johns Hopkins say they have developed a method for finding and killing malignant cells while sparing healthy ones.

The method, called “theranostic” imaging, targets and tracks potent drug therapies directly and only to cancer cells. It relies on binding an originally inactive form of drug chemotherapy, with an enzyme, to specific proteins on tumor cell surfaces and detecting the drug’s absorption into the tumor. The binding of the highly specific drug-protein complex, or nanoplex, to the cell surface allows it to get inside the cancerous cell, where the enzyme slowly activates the tumor-killing drug.

Researchers say their findings, published in the journal American Chemical Society Nano online Aug. 6, are believed to be the first to show that chemotherapies can be precisely controlled at the molecular level to maximize their effectiveness against tumors, while also minimizing their side effects.

Senior study investigator Zaver Bhujwalla, Ph.D., a professor at the Johns Hopkins University School of Medicine and its Kimmel Cancer Center, notes that a persistent problem with current chemotherapy is that it attacks all kinds of cells and tissues, not just cancerous ones.

In the theranostic imaging experiments, overseen by Bhujwalla and study co-investigator Martin Pomper, M.D., Ph.D., investigators directed drugs only to cancer cells, specifically those with prostate-specific membrane antigen, or PSMA cell surface proteins. Both Pomper and Bhujwalla are affiliated faculty members of Johns Hopkins Institute for NanoBioTechnology.

“Our results show a non-invasive imaging approach to following and delivering targeted therapy to any cancer that expresses PSMA,” says Bhujwalla, who also serves as director of the Johns Hopkins In Vivo Cellular and Molecular Imaging Center (ICMIC), where the theranostic imaging studies were developed.

Bhujwalla says the new technique potentially will work against any cancer in which tumors elevate production of certain cell surface proteins. Examples would include breast cancers with HER-2/neu and CXCR4 proteins, and some liver, lung and kidney cancers also known to express particular proteins. She notes that PSMA is expressed in the vessels of most solid tumors, suggesting that the nanoplex reported in the latest study could be used in general to image and treat a variety of cancers.

In their latest series of experiments, primarily in mice injected with human prostate tumor cells, Bhujwalla and the Johns Hopkins team tested their ability to track with imaging devices the delivery of anti-cancer drugs directly to tumors. Some of the tumors comprised cells with PSMA, while other so-called control tumors had none. Included in the drug nanoplex were small strands of RNA, cell construction acids that can be used instead to block and turn down production of a well-known enzyme, choline kinase, whose levels usually rise with tumor growth. All nanoplex components were imaged inside the tumor, in addition to dropping choline kinase production, which decreased by 80 percent within 48 hours of nanoplex absorption into cells with ample PSMA. When researchers used antibodies to block the action of PSMA, down went the level of nanoplex uptake and drug activation in cancerous cells as measured by dimming of the image.

Different concentrations of the drug nanoplex, tagged with radioactive and fluorescent molecules, were mixed in the lab with prostate cancer tissue cells, some of which had extra PSMA and others which had none. Only those cells with extra PSMA showed nanoplex uptake, as measured by image intensity, which later decreased when PSMA-blocking chemicals were added (back to levels seen in cells with almost no PSMA).

Additional experiments involving injections of three different concentrations of the drug nanoplex showed no damage to other vital mouse organs, such as the kidney and liver, nor any uptick in the mouse immune system response.

“Our theranostic imaging approach shows how the best methods of detection and treatment can be combined to form highly specialized, more potent and safer forms of chemotherapy,” says Pomper, a professor at Johns Hopkins who also serves as an associate director at ICMIC.

He says that an important goal for theranostic imaging is to move it beyond standard chemotherapy that attacks one target molecule at a time.

“With theranostic imaging, we can attack multiple tumor targets, making it harder for the tumor to evade drug treatment,” says Pomper, who is already working with colleagues at Johns Hopkins to identify other molecular targets.

The most recent studies were performed at Johns Hopkins over two years, starting in 2010, with funding support from the National Cancer Institute, part of the National Institutes of Health. The corresponding grant numbers are P50-CA103175, RO1-CA138515 and RO1-CA134675.

In addition to Bhujwalla and Pomper, other Johns Hopkins researchers from the Russell H. Morgan Department of Radiology involved in this imaging study were lead investigators Zhihang Chen, Ph.D., and Mary-France Penet, Ph.D. Additional study co-investigators were Sridhar Nimmagadda, Ph.D.; Li Cong, Ph.D.; Sangeeta Banerjee, Ph.D.; Paul Winnard Jr., Ph.D.; Dmitri Artemov, Ph.D.; and Kristine Glunde, Ph.D.

Press release by David March

Therapeutic nanolex containing multi-modal imaging reporters targeted to prostate specific membrane antigen (PSMA), which is expressed on the cell surface of castrate resistant PCa. (Image by Chen et al. from ACS Nano 2012).

 

High schoolers to show off their summer research

Stephanie Keyaka (left) working with Jincy Abraham (Notre Dame) in the Craig Montell Lab. Photo by Mary Spiro.

The Summer Academic Research Experience (SARE) pairs specially selected teens who come from academically disadvantaged homes with university mentors who guide them through a mini research project. The students gain valuable work skills, learn about scientific careers, get tutoring help, practice their writing, gather data for their projects and earn some cash for the future. The group will present their research findings during a poster session at the Johns Hopkins University medical campus on August 20 in the Bodian Room (1830 Building Rm 2-200) from 3:30 to 4:30 p.m.

“This is way better than flipping burgers,” laughed Stephanie Keyaka, as she prepared an image of a Western Blot performed on  Drosophila (fly) eye genes.

Keyaka is one of three high school students who worked in a biological chemistry laboratory  this summer with financial support from Johns Hopkins University Institute for NanoBioTechnology and School of Medicine.

Christopher Miller (right) with his mentor Hoku West-Foyle. Photo by Mary Spiro.

Keyaka, a rising 10th grader from The SEED School of Maryland, will be joined at the poster session by Christopher Miller, also a rising 10th grader from The SEED School of Maryland and Shaolin Holloman, a rising 11th grader at Baltimore Polytechnic Institute who is part of the Boys Hope Girls Hope of Baltimore.

The SEED School of Maryland is a public boarding school that accepts qualified children from across the state entering the 6th grade.  Boys Hope Girls Hope is a privately funded nonprofit that offers students the chance to attend academically challenging public or private schools and the opportunity to live in the Boys Hope or Girls Hope home.

Miller studied the protein myosin in the cell biology laboratory of  associate professor Douglas Robinson. Holloman worked in the cell biology lab of professor Carolyn Machamer on a project that sought to understand why the SARS coronavirus localized in the Golgi apparatus of the cell. Keyaka studied rhodopsin in the eyes of flies the lab of professor Craig Montell.

Shaolin Holloman (left) with professor Carolyn Machamer. Photo by Mary Spiro.

Help celebrate the accomplishments of our summer high school students who participated in the Summer Academic Research Experience. This event is free and open to the entire Hopkins  community. Light refreshments will be served. Students, faculty and mentors will available to discus the projects.

 

 

 

Five Hopkins students conduct nano research in Belgium

Each summer, Johns Hopkins Institute for NanoBioTechnology (INBT) has funding to support several summer research internships abroad. The International Research Experience for Students (IRES) program, funded by the National Science Foundation, provides support for students to work with researchers at The Inter-University MircroElectronics Centre (IMEC) in Leuven, Belgium. Students work at IMEC’s world-class microfabrication facility and learn to design, fabricate and test a wide range of biomedical devices.

Internships can last two to three months, although they can be much shorter depending on the project. They include travel expenses, accommodation and a stipend. The IRES program is open to Johns Hopkins undergraduate and graduate students.

Students are selected through discussions with and recommendation from their advisers. Interns selected must also have a research project that is mutually of interest to investigators at both Johns Hopkins and IMEC. Interested students should contact INBT’s Academic Program Administrator Ashanti Edwards (ashanti@jhu.edu) to being the process of applying for upcoming internships.

During the summer of 2012 five students from Johns Hopkins conducted research at IMEC. They included the following:

Gregg Duncan is a doctoral student in the lab of Michael Bevan, associate professor of chemical and biomolecular engineering. Duncan used dark field microscopy to quantify nanoparticle-cell interactions.

Colin Paul is a doctoral student in the lab of Konstantinos Konstantopoulos, professor and chair of the Department of Chemical and Biomolecular Engineering. Paul brought cell migration devices fabricated in the Konstantopoulos lab to IMEC to perform proof-of-concept experiments with Nicolas Barbera (see below).

Nicolas Barbera is a rising senior working in the Konstantopoulos lab. Barbera gained skills in fluorescence microscopy, dark field microscopy and hyperspectral imaging.

Sarah Friedrich is a doctoral student from the laboratory of Andre Levchenko, professor of biomedical engineering. Friedrich worked on a platform that could expose cells to both chemical and topographical stimulation at the same time.

Peter Nelson is a rising sophomore working in the lab of Jordan Green, assistant professor of biomedical engineering. Nelson worked developing on a polymer-nanoparticle with the ability to apply hyperthermia (heat) and chemotherapy treatments.

Story by Mary Spiro 

Tumor cells change when put into a ‘tight spot’

Konstantinos Konstantopoulos addresses audience at 2012 NanoBio Symposium. Photo by Mary Spiro/JHU

“Cell migration represents a key aspect of cancer metastasis,” said Konstantinos Konstantopoulos, professor and chair of the Department of Chemical and Biomolecular Engineering at Johns Hopkins University. Konstantopoulos was among the invited faculty speakers for the 2012 NanoBio Symposium.

Cancer metastasis, the migration of cancer cells from a primary tumor to other parts of the body, represents an important topic among professors affiliated with Johns Hopkins Institute for NanoBioTechnology. Surprisingly, 90 percent of cancer deaths are caused from this spread, not from the primary tumor alone. Konstantopoulos and his lab group are working to understand the metastatic process better so that effective preventions and treatments can be established. His students have studied metastatic breast cancer cells in the lab by tracking their migration patterns. The group has fabricated a microfluidic-based cell migration chamber that contains channels of varying widths. Cells are seeded at one opening of the channels, and fetal bovine serum is used as a chemoattractant at the other opening of the channels to induce the cells to move across. These channels can be as big as 50 µm wide, where cells can spread out to the fullest extent, or as small as 3 µm wide, where cells have to narrowly squeeze themselves to fit through.

A current dogma in the field of cell migration is that actin polymerization and actomyosin contractility give cells the flexibility they need to protrude and contract across a matrix in order to migrate. When Konstantopoulos’s students observed cells in the wide, 50 µm-wide channels, they saw actin distributed over the entirety of the cells, as expected. They also observed that when the cells were treated with drugs that inhibited actin polymerization and actomyosin contractility, they did not migrate across the channels, also as expected.

However, when the students observed cells in the narrow, 3 µm-wide channels, they were surprised to see actin only at the leading and trailing edges of the cells. Additionally, the inhibition of actin polymerization and actomyosin contractility did not affect the cells’ ability to migrate.

“Actin polymerization and actomyosin contractility are critical for 2D cell migration but dispensable for migration through narrow channels,” concluded Konstantopoulos. The data challenged what many had previously believed about cell migration by showing that cells in confined spaces did not need these actin components to migrate.

These findings are indeed important in the context of cancer metastasis, where cells must migrate through a heterogeneous environment of both wide and narrow areas. Konstantopoulos’s data gives a better mechanistic understanding of the different methods cancer cells use to migrate in diverse surroundings.

Future studies in the Konstantopoulos lab will focus on how tumor cells decide which migratory paths to take. INBT-sponsored graduate student Colin Paul has developed an additional microfluidic device that contains channels with bifurcations. He hopes to determine what factors guide a cell in one direction versus another. The Konstantopoulos lab hopes to continue to understand exactly how tumor cells migrate so that new therapies can eventually be developed to stop metastasis.

Story by Allison Chambliss, a Ph.D. student in the Department of Chemical and Biomolecular Engineering with interests in cellular biophysics and epigenetics.

Watch a video related to this research here.

Konstantopoulos reported these findings in October 2012 The Journal of the Federation of American Societies for Experimental Biology.  Read the article online here.

 

Nanoscale scaffolds spur stem cells to cartilage repair

Scanning electron micrographs showing chondroitin sulfate (CS) and poly(vinyl alcohol)-methacrylate (PVA) nanofibers after electrospinning and processing to render the nanofiber scaffolds water-insoluble. Image by Jeannine Coburn/JHU first appeared in PNAS.

A spun 3-D scaffold of nanofibers did a better job of producing larger quantities of and a more durable type of the cartilage protein than flat, 2-D sheets of fibers did. 

Johns Hopkins tissue engineers have used tiny, artificial fiber scaffolds thousands of times smaller than a human hair to help coax stem cells into developing into cartilage, the shock-absorbing lining of elbows and knees that often wears thin from injury or age.

Reporting online June 4 in the Proceedings of the National Academy of Sciences, investigators say they have produced an important component of cartilage in both laboratory and animal models. While the findings are still years away from use in people, the researchers say the results hold promise for devising new techniques to help the millions who endure joint pain.

“Joint pain affects the quality of life of millions of people. Rather than just patching the problem with short-term fixes, like surgical procedures such as microfracture, we’re building a temporary template that mimics the cartilage cell’s natural environment, and taking advantage of nature’s signals to biologically repair cartilage damage,” says Jennifer Elisseeff, Ph.D., Jules Stein Professor of Ophthalmology and director of the Translational Tissue Engineering Center at the Johns Hopkins University School of Medicine. Elisseeff is also an affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology.

Unlike skin, cartilage can’t repair itself when damaged. For the last decade, Elisseeff’s team has been trying to better understand the development and growth of cartilage cells called chondrocytes, while also trying to build scaffolding that mimics the cartilage cell environment and generates new cartilage tissue. This environment is a three-dimensional mix of protein fibers and gel that provides support to connective tissue throughout the body, as well as physical and biological cues for cells to grow and differentiate.

In the laboratory, the researchers created a nanofiber-based network using a process called electrospinning, which entails shooting a polymer stream onto a charged platform, and added chondroitin sulfate — a compound commonly found in many joint supplements — to serve as a growth trigger. After characterizing the fibers, they made a number of different scaffolds from either spun polymer or spun polymer plus chondroitin. They then used goat bone marrow-derived stem cells (a widely used model) and seeded them in various scaffolds to see how stem cells responded to the material.

Elisseeff and her team watched the cells grow and found that compared to cells growing without scaffold, these cells developed into more voluminous, cartilage-like tissue.

“The nanofibers provided a platform where a larger volume of tissue could be produced,” says Elisseeff, adding that three-dimensional nanofiber scaffolds were more useful than the more common nanofiber sheets for studying cartilage defects in humans.

The investigators then tested their system in an animal model. They implanted the nanofiber scaffolds into damaged cartilage in the knees of rats, and compared the results to damaged cartilage in knees left alone.

They found that the use of the nanofiber scaffolds improved tissue development and repair as measured by the production of collagen, a component of cartilage. The nanofiber scaffolds resulted in greater production of a more durable type of collagen, which is usually lacking in surgically repaired cartilage tissue. In rats, for example, they found that the limbs with damaged cartilage treated with nanofiber scaffolds generated a higher percentage of the more durable collagen (type 2) than those damaged areas that were left untreated.

“Whereas scaffolds are generally pretty good at regenerating cartilage protein components in cartilage repair, there is often a lot of scar tissue-related type 1 collagen produced, which isn’t as strong,” says Elisseeff. “We found that our system generated more type 2 collagen, which ensures that cartilage lasts longer.”

“Creating a nanofiber network that enables us to more equally distribute cells and more closely mirror the actual cartilage extracellular environment are important advances in our work and in the field. These results are very promising,” she says.

Other authors included Jeannine M. Coburn, Matthew Gibson, Sean Monagle and Zachary Patterson, all from The Johns Hopkins University.

From a press release by Audrey Huang.

 

Nanoparticles slip through mucus barrier to protect against herpes virus

“Thick, sticky mucus layers limit effectiveness of drug delivery to mucosal tissues. Mucus-penetrating particles or MPPs (in red) are able to penetrate mucus, covering the entire surface of the mouse vagina (in blue). Improved distribution and retention of MPPs led to significantly increased protection in a mouse model for herpes simplex virus infection. Image by Laura Ensign.

Johns Hopkins researchers say they have demonstrated for the first time, in animals, that nanoparticles can slip through mucus to deliver drugs directly to tissue surfaces in need of protection.

The researchers used these mucus-penetrating particles, or MPPs, to protect against vaginal herpes infections in mice. The goal is to create similar MPPs to deliver drugs that protect humans against sexually transmitted diseases or even treat cancer.

“This is the first in vivo proof that MPPs can improve distribution, retention, and protection by a drug applied to a mucosal surface, said Justin Hanes, Ph.D., a professor of ophthalmology at the Johns Hopkins Wilmer Eye Institute and director of the Center for Nanomedicine at the Johns Hopkins University School of Medicine.

Hanes also is a principal investigator with the Johns Hopkins Center of Cancer Nanotechnology Excellence. Results of his team’s experiments are described in the June 13 issue of the journal Science Translational Medicine.

The moist mucosal surfaces of the body, like the eyes, lungs, intestines and genital tract, are protected from pathogens and toxins by layers of moist sticky mucus that is constantly secreted and shed, forming our outermost protective barrier.

“Although many people associate mucus with disgusting cold and cough symptoms, mucus is in fact a sticky barrier that helps keep you healthy,” says Laura Ensign, a doctoral student affiliated with the Center for Nanomedicine at the School of Medicine and with the Department of Chemical and Biomolecular Engineering at Johns Hopkins’ Whiting School of Engineering. She is the lead author of the journal report.

Unfortunately, Ensign noted, mucus barriers also stop helpful drug delivery, especially conventional nanoparticles intended for sustained drug delivery. In a Johns Hopkins laboratory, researchers developed nanoparticles that do not stick to mucus so they can slip through to reach the cells on the mucosal surface, in this case the surface of the mouse vagina, she added.

Ensign explained that conventional nanoparticles actually stick to mucus before releasing their drug payload and are then removed when the mucus is replenished, often within minutes to hours. Working with researchers in the laboratory of Richard Cone, Ph.D., in the Department of Biophysics in the university’s Krieger School of Arts and Sciences, the Hanes team fabricated particles with surface chemistry that mimics a key feature of viruses that readily infect mucosal surfaces.

“Richard Cone’s lab found that viruses, such as the human papilloma virus, could diffuse through human cervical mucus as fast as they diffuse through water. These ‘slippery viruses’ have surfaces that are ‘water-loving,’ ” Hanes said. “In contrast, many nanoparticles intended to deliver drugs to mucosal surfaces are ‘mucoadhesive’ and ‘oil-loving,’ but these nanoparticles stick to the superficial layers of the mucus barrier, the layers that are most rapidly removed.”

To make their mucus-penetrating particles, the team transformed conventional ‘oil-loving’ nanoparticles by coating them with a substance used in many commercial pharmaceutical products: polyethylene glycol. PEG makes the particles “water-loving,” like the viruses that slip right through mucus.

“The key is that the nanoparticles, like viruses, have to be small enough to go through the openings in the mucus mesh, and also have surfaces that mucus can’t stick to. If you think about it,” said Ensign, “mucus sticks to almost everything.”

“Viruses have evolved over millions of years to become slippery pathogens that readily penetrate our protective mucus barriers,” said Cone, “and engineering nanoparticles that penetrate the mucus barrier just like viruses is proving to be a clever way to deliver drugs.”

Hanes emphasized that the MPPs provided greatly improved protective efficacy while at the same time reducing the effective dose of drug needed 10-fold. Furthermore, Hanes added, the MPPs “continue to supply drug for at least a day and provide nearly 100 percent coverage of the mucosal surface of the vagina and ectocervix” in their laboratory mice.

“We’ve shown that mucus-penetrating particles are safe for vaginal administration in mice. Our next move will be to show that they are safe for vaginal administration in humans,” Ensign said. “Now our laboratory currently is working on an MPP formulation of a drug that protects against HIV infection that we hope will be tested in humans.”

Their technology could lead to a once-daily treatment for preventing sexually transmitted diseases, for contraception and for treatment of cervico-vaginal disorders, Ensign said.

Ensign added that MPP technology has the potential to prevent a wide range of mucosal diseases and infections, including chronic obstructive pulmonary disease, lung cancer, and cystic fibrosis,” Ensign said.

Additional authors on the paper include postdoctoral fellow Ying-Ying Wang and research specialist Timothy Hoen from the Department of Biophysics; former master’s student Terence Tse from the Department of Chemical and Biomolecular Engineering; and Benjamin Tang, formerly of Johns Hopkins School of Medicine and currently at the Massachusetts Institute of Technology.

Under a licensing agreement between Kala Pharmaceuticals and the Johns Hopkins University, Hanes is entitled to a share of royalties received by the university on sales of products used in the study.

Hanes and the university own Kala Pharmaceuticals stock, which is subject to certain restrictions under university policy. Hanes is also a founder, a director and a paid consultant to Kala Pharmaceuticals. The terms of this arrangement are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.”

Story by Mary Spiro

Additional news coverage of this research may be found at the following links:

Phys.org

WYPR: The Mucus Ruse

Scientific American

 

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

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

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

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

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

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

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

At the Whiting School of Engineering…

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

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

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

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

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

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

At the School of Medicine…

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

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

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

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

At the Krieger School of Arts and Sciences…

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

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

 

 

Hruban discusses challenges in pathology at INBT symposium

Dr. Ralph Hruban of the Johns Hopkins School of Medicine at the INBT annual NanoBio Symposium. Photo by Mary Spiro

Pancreatic cancer is well known as one of the most malicious types of cancers. Seventy-five percent of people lose their battle with pancreatic cancer within a year of diagnosis and only 5 percent survive beyond five years.

“There is opportunity for nanotechnology to have an impact,” said Dr. Hruban as he highlighted the many challenges in improving detection and treatment of pancreatic cancers during his talk at the annual Nano-Bio Symposium hosted by Johns Hopkins Institute for NanoBioTechnology on May 4.

Pathologists have been able to determine many histological changes in cancerous pancreatic ducts and also many of the related genetic changes. The challenge is to translate these discoveries in pathology into novel diagnostic tools.

“Early detection is the best hope in fighting cancer,” said Hruban. Nanotechnology could allow for visualization of genetic changes and changes in protein expression in pancreatic lesions which would help in earlier detection.

Treatment of these pancreatic lesions could be better handled with more robust imaging and staining techniques. Thousands of CAT scans are taken at Johns Hopkins hospital every year and doctors began screening all of these CAT scans performed at the hospital to identify pancreatic cysts.

Even with the cysts identified, there is no way to tell if the cyst is benign or malignant without surgery. Hruban gave as an example a female patient that was pregnant who was identified with a pancreatic cyst that turned out to be benign. For months after, the patient had a variety of health problems due to the surgery.

Hruban gave an old folk rhyme about coral snakes as an analogy, “Red on yellow, kill a fellow. Red on black, friend of Jack.” Nanotechnology could provide a means of visualizing which cysts are harmful and prevent patients from having unnecessary surgeries.

Story by Gregg Duncan, a Ph.D. student in the Department of Chemical and Biomolecular Engineering with interests in biomaterials and drug delivery.

In vivo visualization of angiogenesis during wound healing featured on journal cover

Laser speckle contrast images showing (l-r) sequential images of the in vivo blood flow changes that occur on days 0, 3, 5, 7, 10 and 12 after wound creation.

Innovative ways of imaging wound healing can reveal much about blood vessel remodeling and blood flow following an injury. Researchers in the Russell H. Morgan Department of Radiology and Radiological Science and Department of Biomedical Engineering at the Johns Hopkins University School of Medicine have developed a method for using laser speckle contrast imaging (LSCI) to elucidate the changes that occur in the microvasculature over time as a wound heals. Researchers in the laboratory of Arvind P. Pathak have visualized the wound healing process in a mouse ear model by capturing images of angiogenesis—or the development of new blood vessels—over a 12-day period.

“LSCI is a powerful tool for observing the architecture and remodeling of microvasculature as well as the hemodynamic changes (blood flow) during angiogenesis,” said Pathak, an assistant professor of radiology and oncology and principal investigator on the study. “Being able to watch this process occur in a living animal helps us better understand the role of the vasculature during various phases of the wound healing process.”

Stunning images obtained from their experiments were featured on the cover of the March issue of the journal Angiogenesis. The LSCI images shown on the cover from left to right are sequential images of the in vivo blood flow changes that occur on days 0, 3, 5, 7, 10 and 12 after wound creation. The “hotter” colors indicate higher blood flow. The background image is a grayscale LSCI image from an uninjured mouse ear.

Wound healing typically proceeds in three phases, Pathak explained: inflammation (which initiates the immune response and recruits immune cells and molecules to the injury), proliferation (the formation of new blood vessels and epithelium) and remodeling (which removes the vascular scar created during blood vessel formation). LSCI is ideal for imaging the progression of each phase because it can monitor in vivo changes in microvascular architecture and hemodynamics at the same time, he said.

LSCI images are created when tissue illuminated by a laser is photographed through a small aperture, explained Pathak. “The resulting images exhibit a random interference pattern, also called a ‘speckle’ pattern. In blood vessels, this speckle pattern shifts due to the orderly motion of red blood cells, causing a blur over the exposure time of the camera. The degree of blurring in the LSCI image is proportional to the velocity of blood in the vessels and constitutes the biophysical basis of LSCI. Therefore, LSCI can distinguish blood vessels in tissue without any fluorescent dye or contrast agent.”

In this way, Pathak added, LSCI is capable of “wide area mapping” of the tissue, allowing us to measure not only the length and perfusion of blood vessels but their tortuosity (twistiness) and the overall flow of blood to the wound site as healing progresses.

In addition to angiogenesis research, the imaging method has practical applications in drug testing, Pathak said. “Using LSCI alongside a drug study would provide better insight into the efficacy of drug delivery and therapeutic outcome,” he said.

The lead author of the paper was Abhishek Rege, a graduate student in biomedical engineering co-mentored by Pathak and Nitish V. Thakor, professor of biomedical engineering in whose neuroengineering laboratory LSCI was developed. Kevin Rhie, a research technician in Pathak’s laboratory was the other author on this study.

This work was supported jointly by a Johns Hopkins Institute for NanoBiotechnology (INBT) Junior Faculty Pilot Award to Pathak, and grants from the National Institute of Aging and the Department of Health and Human Services to Thakor.

Story by Mary Spiro