Symposium speakers 2015: Piotr Walczak

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 Piotr Walczak, MD, PhD.

Piotr Walczak, MD, PhD

Piotr Walczak, MD, PhD

Piotr Walczak is an assistant professor in the Johns Hopkins School of Medicine Russell H. Morgan Department of Radiology and Radiological Science, Division of Magnetic Resonance (MR) Imaging. He specializes in magnetic resonance research and neuroradiology with an emphasis on stem and progenitor cell transplantation. Dr. Walczak received his MD in 2002 from the Medical University of Warsaw in Poland. He then completed a research fellowship in cell-based therapy for neurodegenerative disorders at the University of South Florida. After a fellowship in cellular imaging at Johns Hopkins University School of Medicine, Dr. Walczak joined the faculty of Johns Hopkins in 2008. He is an affiliated faculty member at the Kennedy Krieger Institute’s F.M. Kirby Research Center and the Institute for Cell Engineering.

Dr. Walczak’s research focuses primarily on noninvasively monitoring the status of stem and progenitor cells transplanted into the disease-damaged central nervous system. Stem cells are labeled with MR contrast agents, such as iron oxide nanoparticles, to precisely determine the position of the cells after transplantation. By modifying the cells using bioluminescence and MR reporter genes, as well as the use of specific promoter sequences, Dr. Walczak is working to extract information about cell survival and differentiation.

Additional speakers will be profiled in the next few weeks. To register your poster and for more details visit http://inbt.jhu.edu/news/symposium/

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

 

INBT engineers coax stem cells to diversify

Growing new blood vessels in the lab is a tough challenge, but a Johns Hopkins engineering team has solved a major stumbling block: how to prod stem cells to become two different types of tissue that are needed to build tiny networks of veins and arteries.

The team’s solution is detailed in an article appearing in the January 2013 print edition of the journal Cardiovascular Research. The article also was published recently in the journal’s online edition. The work is important because networks of new blood vessels, assembled in the lab for transplanting into patients, could be a boon to people whose circulatory systems have been damaged by heart disease, diabetes and other illnesses.

blood-vessel-3-72

Illustration by Maureen Wanjare

“That’s our long-term goal—to give doctors a new tool to treat patients who have problems in the pipelines that carry blood through their bodies,” said Sharon Gerecht, an assistant professor of chemical and biomolecular engineering who led the research team. “Finding out how to steer these stem cells into becoming critical building blocks to make these blood vessel networks is an important step.”

In the new research paper, the Gerecht team focused on vascular smooth muscle cells, which are found within the walls of blood vessels. Two types have been identified: synthetic smooth muscle cells, which migrate through the surrounding tissue, continue to divide and help support the newly formed blood vessels; and contractile smooth muscles cells, which remain in place, stabilize the growth of new blood vessels and help them maintain proper blood pressure.

To produce these smooth muscle cells, Gerecht’s lab has been experimenting with both National Institutes of Health-approved human embryonic stem cells and induced pluripotent stem cells. The induced pluripotent stem cells are adult cells that have been genetically reprogrammed to act like embryonic stem cells. Stem cells are used in this research because they possess the potential to transform into specific types of cells needed by particular organs within the body.

In an earlier study supervised by Gerecht, her team was able to coax stem cells to become a type of tissue that resembled smooth muscle cells but didn’t quite behave properly. In the new experiments, the researchers tried adding various concentrations of growth factor and serum to the previous cells. Growth factor is the “food’ that the cells consume; serum is a liquid component that contains blood cells.

“When we added more of the growth factor and serum, the stem cells turned into synthetic smooth muscle cells,” Gerecht said. “When we provided a much smaller amount of these materials, they became contractile smooth muscles cells.”

This ability to control the type of smooth muscle cells formed in the lab could be critical in developing new blood vessel networks, she said. “When we’re building a pipeline to carry blood, you need the contractile cells to provide structure and stability,” she added. “But in working with very small blood vessels, the migrating synthetic cells can be more useful.”

In cancer, small blood vessels are formed to nourish the growing tumor. The current work could also help researchers understand how blood vessels are stabilized in tumors, which could be useful in the treatment of cancer.

“We still have a lot more research to do before we can build complete new blood vessel networks in the lab,” Gerecht said, “but our progress in controlling the fate of these stem cells appears to be a big step in the right direction.”

In addition to her faculty appointment with Johns Hopkins’ Whiting School of Engineering, Gerecht is affiliated with the university’s Institute for NanoBioTechnology (INBT) and the Johns Hopkins Engineering in Oncology Center.

The lead author of the new Cardiovascular Research paper is Maureen Wanjare, a doctoral student in Gerecht’s lab who is supported both by the INBT, through a National Science Foundation Integrative Graduate Education and Research Traineeship, and by the NIH. Coauthors of the study are Gerecht and Frederick Kuo, who participated in the research as an undergraduate majoring in chemical and biomolecular engineering. The human induced pluripotent stem cells used in the study were provided by Linzhao Cheng, a hematology professor in the Johns Hopkins School of Medicine.

This research was supported by an American Heart Association Scientist Development Grant and NIH grant R01HL107938.

Original press release can be found here.

 

Gerecht wins NSF CAREER Award for work in blood vessel formation

Sharon Gerecht (Photo:Will Kirk/JHU)

Sharon Gerecht, assistant professor in Chemical and Biomolecular Engineering at Johns Hopkins University, has been awarded the Faculty Early Career Development (CAREER) Award from the National Science Foundation. The $450,000 prize over five years will help Gerecht in her investigation into how hypoxia, or decreased oxygen, affects the development of blood vessels.

Gerecht’s interdisciplinary research brings together her expertise in stem cell and vascular biology with her background in engineering.  Gerecht said she hopes to discover the mechanisms and pathways involved in the formation of vascular networks, as they relate to embryonic development and diseases such as cancer.

Many medical conditions, such as cancer and heart disease, create areas of decreased oxygen or hypoxia in the spaces between cells. But oxygen is required to maintain normal tissue function by blood vessel networks, which bring nutrients to cells. Likewise, the differentiation of stem cells into more complex organs and structures needs a plentiful supply of oxygen from the vasculature to function.

Gerecht’s study will examine how low oxygen levels impact the growth factors responsible for promoting vascular networks. She also will study the growth of vascular networks in engineered hydrogels that mimic the physical attributes of the extracellular matrix, which is the framework upon which cells divide and grow. Finally, her laboratory will focus on discovering how stem cells differentiate to blood vessel cells and assemble into networks under hypoxic conditions.

She will conduct her research through her role as a project director at the Johns Hopkins Engineering in Oncology Center (EOC), a Physical Science-Oncology Center of the National Cancer Institute. Gerecht is also an associated faculty member of the Johns Hopkins Institute for NanoBioTechnology, which administers the EOC.

Gerecht earned her doctoral degree from Technion – Israel Institute of Technology followed by postdoctoral training at Massachusetts Institute of Technology. She joined the faculty of the Whiting School of Engineering at Johns Hopkins in 2007.

The prestigious CAREER award, given to faculty members at the beginning of their academic careers, is one of NSF’s most competitive awards and emphasizes high-quality research and novel education initiatives. It provides funding so that young investigators have the opportunity to focus more intently on furthering their research careers.

Story by Mary Spiro