NCI grant establishes center to advance cancer curing goals

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


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

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

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

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


Denis Wirtz

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

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

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

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

Ken Pienta

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

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

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



Oxygen’s role in cancer spread

Cancer cells need oxygen to survive, as do most other life forms, but scientists had never tracked their search for oxygen in their early growth stages until now — a step toward a deeper understanding of one way cancer spreads that could help treat the disease.

In a paper published online by the Proceedings of the National Academy of Sciences, bioengineers from Johns Hopkins University and the University of Pennsylvania report results of their work showing how sarcoma cells in mice pursue a path toward greater concentrations of oxygen, almost as if they were following a widening trail of breadcrumbs. That path is suggested to lead the cells to blood vessels, through which the cells can spread to other parts of the body.

Oxygen-front.svg“If you think about therapeutic targets, you could target this process specifically,” said Sharon Gerecht, professor in Johns Hopkins University’s Whiting School of Engineering’s Department of Chemical and Biomolecular Engineering and a lead author of the study. She acknowledged that clinical application is a long way off, but said these results reached after three years of study in her laboratory provide clues about a key part of the life cycle of soft-tissue sarcomas and also a proven way to test cancer treatments in the lab. (Gerecht is an associate director of Johns Hopkins Institute for NanoBioTechnology.)

Sarcoma is a cancer that affects connective tissue, including bones, muscles, tendons, cartilage, nerves, fat and some blood vessels.  The study focused specifically on soft tissue sarcoma that does not affect bones, a type diagnosed in some 13,000 patients a year in the United States. Roughly a quarter to half of those patients develop recurring and spreading, or metastasizing, cancer.

Cancers of all sorts are known to thrive with little oxygen, and researchers have looked at the role of low oxygen conditions in tumor development. Less well understood is how cancer cells respond to varying oxygen concentrations in their early stages. That was the focus of this research.

Gerecht and her seven co-authors – four affiliated with Johns Hopkins, three with Penn – tracked thousands of early stage cancer cells taken from mice as they moved through a mockup of bodily tissue made of clear gel in a petri dish.  The hydrogel – a water-based material with the consistency of gelatin – replicates the environment surrounding cancer cells in human tissue.

Kyung Min Park, then a postdoctoral researcher in the Johns Hopkins lab, developed the hydrogel-cancer cell system, and Daniel Lewis, a Johns Hopkins graduate student, analyzed cellular migration and responses to rising oxygen concentrations, or “gradients.”

For this experiment, the hydrogels contained increasing concentrations of oxygen from the bottom of the hydrogel to the upper layer.  That allowed researchers to track how cancer cells respond to different levels of oxygen, both within a tumor and within body tissues.

Analysis of sarcoma tumors in mice, for instance, shows that the largest tumors have a large area of very low oxygen at the center. Smaller tumors have varying oxygen concentrations throughout.

The researchers’ first step was to show that cancer cells migrate more in low-oxygen or “hypoxic” hydrogels as compared with hydrogels containing as much oxygen as the surrounding atmosphere. They then looked at the direction of the cell movement.

In the hydrogel, which mimics the oxygen concentrations in smaller tumors, cells were found to move from areas of lower oxygen to higher. Researchers also found that the medication minoxidil – widely used to treat hair loss and known by its trade name Rogaine – stopped the movement of cancer cells through the hydrogel.

Cancer cells are known to modify their environment to make it easier for them to move through it, but this study takes that understanding a step further, Gerecht said.

“We did not know it was the oxygen” that effectively directs the movement, she said. “It’s suggesting oxygen gradient affects early stages of the metastasis process.”

The study also demonstrates the three-dimensional hydrogel model as an effective tool for testing cancer treatments in a laboratory, the authors wrote. Gerecht said a human patient’s cancer cells could be placed into the hydrogel just as the mouse cells were, allowing clinicians to see how they respond before treatments are given to patients.

The research was supported by the National Cancer Institute (grants CA153952 and CA158301), the American Heart Association (61675), the National Science Foundation (1054415) and Johns Hopkins University’s President’s Frontier Award.

Story by Arthur Hirsch:

Professional development seminar on theranostics April 5

What are theranostics?

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.

Martin Pomper

Martin Pomper

According to Martin G. Pomper, the William R. Brody Professor of Radiology at the Johns Hopkins School of Medicine, the technique 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.

Pomper, an affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology (INBT), is director of the Small Animal Imaging Resource Program (SAIRP) at Johns Hopkins and Deputy Director of the In Vivo Cellular and Molecular Imaging Center (ICMIC). He will will present the INBT professional development seminar, “Forays into Theranostics,” at 2 p.m. on Tuesday, April 5 in Croft G40 on the Homewood campus. Light refreshments will be served.

Seating is limited. RSVP to

Media inquires should be directed to INBT science writer Mary Spiro at


Pushing past challenges in undergraduate research

When I first applied to Johns Hopkins University, I was convinced I did not want to study engineering. I was hesitant to participate in any kind of research and wasn’t all that confident in my technical skills. I thought research would be boring and perhaps unnecessarily difficult. Still, I enjoyed biology and chemistry in high school, so I figured I would major in either one of those two subjects. After taking an engineering sampler seminar course, I found myself attracted to chemical and biomolecular engineering (ChemBE). I still had my reservations about majoring in it, but I’m not one to shy away from a challenge. So, I told myself: if I absolutely hate it, I’ll switch to something different, and if I like it, great, I’ll stick with it. And it turned out that I loved it.

Fatima Umanzor works in the laboratory of Denis Wirtz (photo by Mary Spiro)

Fatima Umanzor works in the laboratory of Denis Wirtz (photo by Mary Spiro)

After a semester of taking introductory chemistry and physics classes, I sat down with my faculty advisor, Dr. Denis Wirtz, and he asked me if I had thought about research. I told him that I had and that I really wanted to work in his lab, even if it meant waiting for a spot to open up. Smiling, he told me it would be no problem. I got an email in the late summer from my soon-to-be mentor, Hasini Jayatilaka, asking whether I would be interested in interviewing to work for her. Excited, I replied that I would be and we met soon after. Since then, my perception of research has changed for the better.

These days, I can be found in the lab most of the time, with the exception of weeks filled with midterms. When I’m not in class, I may be in the cell culture room making 3D type I collagen I matrices or conducting immunofluorescence staining, or in the bacterial room performing an RNA extraction for PCR, or in the office space, analyzing data. With each experiment that we run, I learn something new. Most of what I know about the way cancer works comes from the research that I’ve conducted related to cancer cell metastasis in Dr. Wirtz’s lab, which is a part of the Institute for NanoBioTechnology (INBT). I continue to learn more from these investigations than I do in the classroom. I’ve gained so many new skills that I know will be invaluable one day should I decide to pursue my own PhD or work in an industrial setting.

But I’ve gained so much more than just research experience: I’ve become more confident in my ability to learn and grow as a student and researcher, my mentor and peers in the lab have become sources of advice and wisdom, as well as some of my closest friends, and I’ve been exposed to so many cool opportunities I didn’t know I had before. For example, this summer I was able to participate in a Research Experience for Undergraduates (REU) program at the University of Pittsburgh, and I’m certain that I have my lab experience (and Dr. Wirtz) to thank for making that experience possible.

While there are days that I feel like I’m not cut out for ChemBE, I can always come back to my research team and feel assured that I’m exactly where I’m supposed to be. Between team outings and hearing stories of past experiences, I know that I am not alone when times get hard. And while at times I struggle to deal with discouraging exam grades or frustratingly difficult problem sets, I know that my experiences more than make up for flaws in other aspects and that the time spent on my work in the lab is not in vain. I am lucky enough to work for someone who sees a lot of potential in me, even when I don’t see it in myself, and pushes me to pursue various opportunities and believes in me. That belief and support is a priceless part of what I get from working in the INBT.

Overall, I would say research is one of the most rewarding aspects of my undergraduate career. I’ve made friends, gained an assortment of skills and a lot of new knowledge, and have learned more about myself and potential post-grad opportunities. I’m grateful I can come into a space every day with a purpose and set goals for myself, surrounded by people who are passionate about their work, and be motivated to work hard and discover something new each day.

Fatima Umanzor is a junior studying chemical and biomolecular engineering with a concentration in molecular and cellular bioengineering and an interest in cancer metastasis and tumorigenesis.

All press inquiries about INBT should be directed to Mary Spiro, INBT’s science writer and media relations director at



Symposium speakers 2015: Martin Pomper

Neuro X is the title and theme for the May 1 symposium hosted by Johns Hopkins Institute for NanoBioTechnology. The event kicks off with a continental breakfast at 8 a.m. in the Owens Auditorium, between CRB I and CRB II on the Johns Hopkins University medical campus. Talks begin at 9 a.m. Posters featuring multidisciplinary research from across many Hopkins divisions and departments will be on display from 1 p.m. to 4 p.m.

One of this year’s speakers is Martin G. Pomper, MD, PhD.

Martin Pomper, MD, PhD

Martin Pomper, MD, PhD

Martin Pomper is the William R. Brody Professor of Radiology at the Johns Hopkins School of Medicine, with a joint appointment in Chemical and Biomolecular Engineering at the Whiting School of Engineering. He received his undergraduate, graduate (organic chemistry) and medical degrees from the University of Illinois at Urbana-Champaign. His postgraduate medical training was at Johns Hopkins and included an internship (Osler Medical Service), residencies (diagnostic radiology and nuclear medicine) and fellowship (neuroradiology). He is board-certified in diagnostic radiology and nuclear medicine. He has been on the Radiology faculty at Johns Hopkins since 1996. He is currently the director of the Johns Hopkins Small Animal Imaging Resource and associate director of the In Vivo Cellular and Molecular Imaging Center, both funded by the National Cancer Institute to support molecular imaging research.

Dr. Pomper is director of the Johns Hopkins Center for Translational Molecular Imaging. He is co-director of the Johns Hopkins Center of Cancer Nanotechnology Excellence and the Positron Emission Tomography Center. His interests are in the development of new radiopharmaceuticals, optical probes and techniques for molecular imaging of cancer and central nervous system disease. His research group consists of chemists, physicists, molecular biologists and clinicians working together toward clinical molecular imaging. He is Editor-in-Chief of Molecular Imaging and a past President of the Society of Nuclear Medicine’s Molecular Imaging Center of Excellence. He has numerous patents related to medical imaging, many of which have been licensed, as well as several imaging agents in clinical trials.

Additional speakers will be profiled in the next few weeks. To register your poster and for more details visit

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, or 410-516-4802.

New eyes for diagnostics

Initial medical diagnoses are done based on physical examination by a health care professional. However, as the technology of optics, computing, and biology continues to advance, engineers have essentially developed “enhanced eyes” for health care professionals to see beyond the limits of our natural vision to diagnose patients. For example, with the advent of ultrasound, doctors are able to see into a pregnant mother’s womb to monitor the health of a developing baby.

Figure 1: How imaging modalities are being combined to more precisely diagnose patients. In this image high levels of cell activity are being identified to pinpoint cancer existence. Source:

Figure 1: How imaging modalities are being combined to more precisely diagnose patients. In this image high levels of cell activity are being identified to pinpoint cancer existence. Source:

New imaging techniques and machines are combining existing modalities. This improves diagnoses and combines the strengths of each imaging modality. For example, cancer diagnosis can now be achieved by scanning a patient with a dual PET/CT machine (Fig. 1). In this method, imaging specialists combine the strength of CT scans, which shows high resolution of organ location and tissue distribution, and PET scans, which determines molecular/cellular activity by introducing a radioactive molecule into the body.

These technologies have also increased our understanding of diseases and are used frequently in research to develop new theories for disease mechanisms. Nevertheless, because of the amount of technology and engineering that has gone into developing these machines, they are still very costly both to patients and researchers.

About the author: John Hickey is a second year Biomedical Engineering PhD candidate in the Jon Schneck lab researching the use of different biomaterials for immunotherapies and microfluidics in identifying rare immune cells.

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, or 410-516-4802.

How firefly research helped gene therapy

Sometimes on a calm summer or fall night, one is able to observe the beautiful dance of blinking fireflies. Scientists began to explore mechanisms to describe this unique natural phenomenon as early as the late 1800’s. After a series of experiments with solutions at different temperature with ground up abdomens of fireflies, Raphael Dubois named the enzyme luciferase and the substrate luciferin that were the cause of the light-producing reaction (1).  But it wasn’t until recently in 1985 that scientists were able to clone the gene for luciferase and express it in bacteria to produce the luciferase.


Figure 1: Picture of firefly. Source:

Once the gene was cloned, genetic researchers realized the importance of the findings and started to use it as a reporter gene for experimental gene therapy. Gene therapies involve transfection of new genetic material into the host’s DNA and can be applied not only for therapies for diseases of genetic origin, but can be used for cancer therapy and diagnostic purposes.

By incorporating the gene for luciferase along with the gene of interest, the Hai-Quan Mao lab in the Department of Materials Science and Engineering at Johns Hopkins University can detect whether or not their nanoparticles used for gene delivery have been successful simply by adding luciferin to the cells. If the gene transfer was successful, then the luciferase will act on the substrate luciferin to emit light.


1)     Fraga, Hugo. “Firefly luminescence: A historical perspective and recent developments.” Photochemical & Photobiological Sciences 7.2 (2008): 146-158.

About the author: John Hickey is a second year Biomedical Engineering PhD candidate in the Jon Schneck lab researching the use of different biomaterials for immunotherapies and microfluidics in identifying rare immune cells.

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, or 410-516-4802.


Drug-chemo combo destroys challenging breast cancer stem cells

Gregg Semenza

Gregg Semenza

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

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

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

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

Read the PNAS article here.

Visit the PS-OC website here.

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


Podcast: Artificial blood vessel visualizes cancer cell journey

Researchers from Johns Hopkins Institute for NanoBioTechnology are visualizing many of the steps involved in how cancer cells break free from tumors and travel through the blood stream, potentially on their way to distant organs.  Using an artificial blood vessel developed in the laboratory of Peter Searson, INBT director and professor of materials science and engineering, scientists are looking more closely into the complex journey of the cancer cell.

Figure 1. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a functional vessel immunofluorescently stained for PECAM-1 (green) and nuclei (blue).

Figure 1. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a functional vessel immunofluorescently stained for PECAM-1 (green) and nuclei (blue). (Wong/Searson Lab)

INBT’s science writer, Mary Spiro, interviewed device developer Andrew Wong, a doctoral student Searson’s  lab, for the NanoByte Podcast. Wong is an INBT training grant student. Listen to NANOBYTE #101 at this link.

Wong describes the transparent device, which is made up of a cylindrical channel lined with human endothelial cells and housed within a gel made of collagen, the body’s structural protein that supports living tissues. A small clump of metastatic breast cancer cells is seeded in the gel near the vessel while a nutrient rich fluid was pumped through the channel to simulate blood flow. By adding fluorescent tags the breast cancer cells, the researchers were able to track the cells’ paths over multiple days under a microscope.

VIDEO: Watch how a cancer cell approaches the artificial blood vessel, balls up and then forces its way through the endothelial cells and into the streaming fluids within the channel of the device. (Video by Searson Lab)

The lab-made device allows researchers to visualize how “a single cancer cell degrades the matrix and creates a tunnel that allows it to travel to the vessel wall,” says Wong. “The cell then balls up, and after a few days, exerts a force that disrupts the endothelial cells. It is then swept away by the flow. “

Wong said his next goal will be to use the artificial blood vessel to investigate different cancer treatment strategies, such as chemotherapeutic drugs, to find ways to improve the targeting of drug-resistant tumors.

Results of their experiments with this device were published in the journal Cancer Research in September.

Andrew Wong (left) and Peter Searson. (Photo by Will Kirk/Homewood Photography)

Andrew Wong (left) and Peter Searson. (Photo by Will Kirk/Homewood Photography)

Check out this gallery of images from the Searson Lab. The captions are as follows:
Figure 1. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a functional vessel immunofluorescently stained for PECAM-1 (green) and nuclei (blue).
Figure 2. 3D projection of a confocal z-stack shows human umbilical vein endothelial cells (HUVECs) forming a vessel with dual-labeled MDA-MB-231 breast cancer cells on the periphery.
Figure 3. Phase-contrast and fluorescence overlays depicting a functional vessel comprised of human umbilical vein endothelial cells (HUVECs) with dual-labeled MDA-MB-231 breast cancer cells on the periphery (green in the nucleus, red in the cytoplasm).

For all press inquiries regarding INBT, its faculty and programs, contact Mary Spiro, or 410-516-4802.


Jordan Green named to PopSci’s Brilliant Ten

Jordan Green, Johns Hopkins University associate professor of biomedical engineering and executive committee member for the Johns Hopkins Institute for NanoBioTechnology, was named one of Popular Science magazine’s Brilliant Ten. The magazine recognized “inspired young scientists and engineers … whose ideas will transform the future.”

Jordan Green (Photo by Marty Katz)

Jordan Green (Photo by Marty Katz)

Green’s work focuses on using nanoscale particles made in the shape of footballs that can train the body’s own immune system to tackle cancer cells. Turns out, particles with the elongated ovoid shape have a slightly larger surface area, which gives them an edge over spherical particles. The football-shaped particles did a better job of triggering the immune system to attack the cancer cells.

Green collaborated with Jonathan Schneck, M.D., Ph.D., professor of pathology, medicine and oncology at Johns Hopkins School of Medicine. Both are affiliated faculty members of Johns Hopkins Institute for  NanoBioTechnology. Their work was published in the journal Biomaterials on Oct 5, 2013.

Read more about their research here.

Congratulations to Dr. Green for the recognition of your interesting and promising work!

Watch a video where Green explains his work in simple terms using toys.