Q & A with Peter Devreotes

Back when the Johns Hopkins Institute for NanoBioTechnology first formed, we had an executive committee with faculty members from every University division to help guide our early footsteps. One of those memebers was Peter Devreotes, professor of cell biology at the School of Medicine.

Peter Devreotes with postdoctoral fellow Huaqing Cai. (Photo: Marty Katz)

Peter Devreotes with postdoctoral fellow Huaqing Cai. (Photo: Marty Katz)

Over the years Devreotes has advised and mentored students from the high school to postdoctoral level who are associated with INBT in his laboratory. Here, we have a short question and answer with Devreotes, produced for the Institute for Basic Biomedical Sciences newsletter. We e get to know a little bit about this faculty member, his personal and research interests and what inspires him.

How did you decide to study science?

DEVREOTES: I never thought about anything else. My father taught me a lot of math and took me on nature walks. I developed this fascination with everything in nature and wanted to know how it worked—I still do. I was actually a physics major in college—didn’t take a single biology class-but I decided to do a Ph.D. in biophysics, at Johns Hopkins’ Homewood campus. I was immediately fascinated by the mechanics of cells.

Follow this link to read more from this interview.

 

Cancer spreads through ‘Rock’ and ‘Rho’

n low oxygen conditions, breast cancer cells form structures that facilitate movement, such as filaments that allow the cell to contract (green) and cellular ‘hands’ that grab surfaces to pull the cell along (red). Credit: Daniele Gilkes

In low oxygen conditions, breast cancer cells form structures that facilitate movement, such as filaments that allow the cell to contract (green) and cellular ‘hands’ that grab surfaces to pull the cell along (red).
Credit: Daniele Gilkes

ROCK1 and RhoA genes found partly to blame for cancer metastasis. Gregg Semenza, co-director of the Johns Hopkins Physical Sciences-Oncology Center (PS-OC), led a team that made the discovery. The following comes from a Johns Hopkins press release:

Biologists at The Johns Hopkins University have discovered that low oxygen conditions, which often persist inside tumors, are sufficient to initiate a molecular chain of events that transforms breast cancer cells from being rigid and stationary to mobile and invasive. Their evidence, published online in Proceedings of the National Academy of Sciences on Dec. 9, underlines the importance of hypoxia-inducible factors in promoting breast cancer metastasis.

“High levels of RhoA and ROCK1 were known to worsen outcomes for breast cancer patients by endowing cancer cells with the ability to move, but the trigger for their production was a mystery,” says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine and senior author of the article. “We now know that the production of these proteins increases dramatically when breast cancer cells are exposed to low oxygen conditions.”

To move, cancer cells must make many changes to their internal structures, Semenza says. Thin, parallel filaments form throughout the cells, allowing them to contract and cellular “hands” arise, allowing cells to “grab” external surfaces to pull themselves along. The proteins RhoA and ROCK1 are known to be central to the formation of these structures.

Moreover, the genes that code for RhoA and ROCK1 were known to be turned on at high levels in human cells from metastatic breast cancers. In a few cases, those increased levels could be traced back to a genetic error in a protein that controls them, but not in most. This activity, said Semenza, led him and his team to search for another cause for their high levels.

What the study showed is that low oxygen conditions, which are frequently present in breast cancers, serve as the trigger to increase the production of RhoA and ROCK1 through the action of hypoxia-inducible factors.

“As tumor cells multiply, the interior of the tumor begins to run out of oxygen because it isn’t being fed by blood vessels,” explains Semenza. “The lack of oxygen activates the hypoxia-inducible factors, which are master control proteins that switch on many genes that help cells adapt to the scarcity of oxygen.” He explains that, while these responses are essential for life, hypoxia-inducible factors also turn on genes that help cancer cells escape from the oxygen-starved tumor by invading blood vessels, through which they spread to other parts of the body.

Daniele Gilkes, Ph.D., a postdoctoral fellow at the PS-OC and lead author of the report, analyzed human metastatic breast cancer cells grown in low oxygen conditions in the laboratory. She found that the cells were much more mobile in the presence of low levels of oxygen than at physiologically normal levels. They had three times as many filaments and many more “hands” per cell. When the hypoxia-inducible factor protein levels were knocked down, though, the tumor cells hardly moved at all. The numbers of filaments and “hands” in the cells and their ability to contract were also decreased.

When Gilkes measured the levels of the RhoA and ROCK1 proteins, she saw a big increase in the levels of both proteins in cells grown in low oxygen. When the breast cancer cells were modified to knock down the amount of hypoxia-inducible factors, however, the levels of RhoA and ROCK1 were decreased, indicating a direct relationship between the two sets of proteins. Further experiments confirmed that hypoxia-inducible factors actually bind to the RhoA and ROCK1 genes to turn them on.

The team then took advantage of a database that allowed them to ask whether having RhoA and ROCK1 genes turned on in breast cancer cells affected patient survival. They found that women with high levels of RhoA or ROCK1, and especially those women with high levels of both, were much more likely to die of breast cancer than those with low levels.

“We have successfully decreased the mobility of breast cancer cells in the lab by using genetic tricks to knock the hypoxia-inducible factors down,” says Gilkes. “Now that we understand the mechanism at play, we hope that clinical trials will be performed to test whether drugs that inhibit hypoxia-inducible factors will have the double effect of blocking production of RhoA and ROCK1 and preventing metastases in women with breast cancer.”

Other authors of the report include Lisha Xiang, Sun Joo Lee, Pallavi Chaturvedi, Maimon Hubbi and Denis Wirtz of the Johns Hopkins University School of Medicine.

This work was supported by grants from the National Cancer Institute (U54-CA143868), the Johns Hopkins Institute for Cell Engineering, the American Cancer Society and the Susan G. Komen Breast Cancer Foundation.

TO BE RESCHEDULED: Shashi Murthy of Northeastern University

THIS SEMINAR HAS BEEN CANCELLED DUE TO THE THREAT OF A WINTER STORM AND WILL BE RESCHEDULED.

“Ever heard about seaweed, Mucinex®, stem cells, and the International Space Station in the same conversation?” is the name of the talk to be given by Johns Hopkins University alumni Shashi Murthy, PhD, at 10:30 am on Thursday, February 13 in the Shriver Hall Clipper Room.  The talk is free and open to the Hopkins community and sponsored by Johns Hopkins Institute for NanoBioTechnology.

Shashi Murthy

Shashi Murthy

Shashi Murthy is an associate professor in the Department of Chemical Engineering and Founding Director of the  Michael J. and Ann Sherman Center for Engineering Entrepreneurship Education at Northeastern University. This presentation will combine a scientific description of a methodology for stem cell purification designed in by the Murthy laboratory with the story of its ongoing commercialization.  Murthy will also talk about how the vision behind the Michael J. and Ann Sherman Center for Entrepreneurship Education came into being and how this Center is impacting the undergraduate experience in the College of Engineering at Northeastern University.

DEADLINE EXTENDED: Applications accepted for INBT IRES until Feb 14

If you have been curious to discover what laboratory work is like in another country, now is your chance to apply for one of INBT’s coveted positions as an international undergraduate researcher. Applications are now being accepted for our National Science Foundation funded International Research Experience for Undergraduates in Leuven, Belgium with IMEC.  The deadline for applications is February 14, 2014. The opportunities are for Johns Hopkins University students.

IMEC clean roomIMEC boasts world-class micro- and nano-fabrication facilities and a campus with more than 1,000 researchers from around the globe who are collaborating on leading-edge projects. Belgium boasts waffles, beer and chocolate. Really, you can’t go wrong here.

INBT international research internships focus on a project of mutual interest to Johns Hopkins faculty and to IMEC investigators. INBT has a long-standing research collaboration agreement with IMEC, one of the world’s leading research organizations focusing on silicon nanotechnology headquartered in Leuven, Belgium. Since 2009, students, both undergraduates and postgraduates, from INBT labs have had the opportunity to participate in internships at IMEC’s state-of-the-art research facility. These internships have the dual purpose of providing international research experience for students as well as furthering the research interests of both Hopkins and IMEC.

To read about some of the previous experiences of our IRES participates, visit INBT’s Summer at IMEC blog here.

To apply, send the following items to Tom Fekete, INBT’s director of corporate partnerships, before Feb. 1: tfekete1@jhu.edu.

  • CV/Resume
  • Research Statement
  • Letter of Recommendation

If you are not sure what you would like to work on, Tom has a list of possible research areas that you can inquire about as well. If you have any questions, please feel free to contact Tom.  If he is unavailable, please contact Ashanti Edwards, INBT’s Academic Program Administrator at ashanti@jhu.edu.

Student engineers solve village problems through Global Engineering Innovation Program

Johns Hopkins Institute for NanoBioTechnology hosts teams of students to travel to foreign countries to apply their engineering skills to solve local problems through a program called Global Engineering Innovation. This story, featured in the Johns Hopkins Gazette, describes one of those projects in Nazaçu, along the Amazon River in Brazil: the design and production of a safer cassava mill that reduces the risk of injury. INBT has also hosted teams in Tanzania and India.

GEU design team with the finalized pedal power grain mill in Tanzania (from left to right) Kristen Kosielski, Jeannine Coburn, Iwen Wu and local resident Jackson. (Photo courtesy Jeannine Coburn)

GEU design team with the finalized pedal power grain mill in Tanzania (from left to right) Kristen Kosielski, Jeannine Coburn, Iwen Wu and local resident Jackson. (Photo courtesy Jeannine Coburn)

Said program director Jennifer Elisseeff, the Jules Stein Professor of Ophthalmology at the Wilmer Eye Institute: “This program has enormous potential to have students visit various communities around the world to design and solve real problems that can help people in their daily lives.”

Read more from the Gazette article here.

Read more about the INBT GEI program here.

 

Science writers’ bootcamp focuses on neuroscience

The sixth annual Johns Hopkins Science Writers’ Boot Camp will feature Johns Hopkins experts in neuroscience and medicine discussing the latest in mapping the brain, learning and memory, recovery after brain injury and more.

WHEN: Monday, April 28, 2014, 9 a.m. to 4:30 p.m. with reception following

WHERE: The National Press Club, 529 14th St. NW, Washington, DC 20045

For more information please visit this link. 

swbc14Confirmed speakers:

  • Marilyn Albert, Ph.D., Director of the Division of Cognitive Neuroscience in the Department of Neurology
  • Amy Bastian, Ph.D., Professor of Neuroscience and member of Kennedy Krieger Institute
  • Henry Brem, M.D., Harvey Cushing Professor and Chairman of the Department of Neurosurgery
  • Aravinda Chakravarti, Ph.D., Professor of Medicine
  • David Foster, Ph.D., Assistant Professor of Neuroscience
  • Argye Hillis, M.D., M.A., Executive Vice Chair of the Department of Neurology and Co-Director of the Cerebrovascular Division
  • Richard Huganir, Ph.D., Director of the Solomon H. Snyder Department of Neuroscience and Co-director of the Brain Science Institute
  • John Krakauer, M.D., Director of the Center for the Study of Motor Learning and Brain Repair
  • David Linden, Ph.D., Professor of Neuroscience
  • Mollie Meffert, M.D., Ph.D., Associate professor of Biological Chemistry
  • Jeffrey Rothstein, M.D., Ph.D., Director of the Robert Packard Center for ALS Research and Director of the Brain Science Institute
  • Hongjun Song, Ph.D., Director of the Stem Cell Program at the Institute for Cell Engineering

 

Interning in INBT’s animation studio

Students from the Maryland Institute College of Art, aka MICA, have been interning at the Johns Hopkins Institute for NanobioTechnology’s Animation Studios pretty much since the studio came into existence in 2007. Studio director and INBT web guru Martin Rietveld organizes the student internships each semester and every summer.

Anny Lai.

Anny Lai.

Most evenings, MICA graphic design major Anny Lai can be found in the INBT animation computer lab working on animating the process of stem cell based tissue regeneration. She has blogged about her experience here.

For more information about internships with INBT, which are open to JHU students, MICA students and others training in the arts, go to this link. Programs used in the animation studio include Cinema 4D, AfterEffects and Adobe Flash.

Even students without training or a background in the arts are welcome to take Martin’s independent study course in animation. Students in engineering and the basic sciences have created smaller animation projects that they use in academic presentations or have submitted to peer-reviewed journals for publication.

Contact Martin at rietveld@jhu.edu for more information.

What is INBT?

At Johns Hopkins University, the Institute for NanoBioTechnology is sort of a strange hybrid animal— a unique entity in academia. Founded in 2006, we are a virtual center that draws faculty membership from four divisions – the medical school, engineering school, school of arts and sciences and from public health.

Four different divisions comprise INBT.

Four different divisions comprise INBT.

Two faculty members, Peter Searson, the Joseph R. and Lynn C. Reynolds Professor in the Department of Materials Science and Engineering, and Denis Wirtz, the Theophilus H. Smoot Professor in the Department of Chemical and Biomolecular Engineering, started INBT. They thought it made sense to combine the efforts of people in engineering with people working in the medical and basic sciences as well as in public health to better solve problems in health care. We have more than 220 affiliated faculty members. There are no other centers or institutes at Hopkins with as many participants from as many different disciplines.

Any faculty member can become a member of INBT; they just have to have an interest in incorporating nanobiotechnology—or science at the scale of just a few atoms—into their research. Researchers at INBT are working on everything from drug delivery systems to solving problems in basic science and engineering using nanobiotechnology.

Physically, INBT is located on the Johns Hopkins Homewood campus in Suite 100 of Croft Hall. That’s where our administrative offices are and some of our faculty members have laboratories in this building. But our research occurs wherever our faculty members are working, and much of that is at the School of Medicine. In fact, nearly half of our members come from the medical school. Faculty members in other divisions are mostly likely collaborating with people at the School of Medicine.

At INBT, we search for funding opportunities for our members and offer small seed grants that help collaborators launch projects. Sometimes these projects are later funded and sustained by larger federal grants. We feel good about helping new ideas find “legs”.

In addition, we train up-and-coming scientists and engineers from high school through the postdoctoral level in our affiliated labs. These include short-term summer programs as well as highly competitive government funded research experiences and fellowships that last several years. INBT is educating the next generation of researchers who will solve problems at the interface of science, engineering and medicine. Our graduate students who fulfill specific requirements are awarded a Certificate of Advanced Study in NanoBioTechnology.

We have global outreach programs as well. INBT has funded research teams to India and Tanzania to solve engineering problems in local communities. Sometimes the challenges are medical, and sometimes they are purely engineering, but the teams much use local materials and resources to accomplish their goals.

Finally, we have industry affiliations. By working with companies in the U.S. and worldwide, we are developing training opportunities for our students that result in the development of new knowledge and hopefully new patented and marketable products. We don’t want to keep our innovations in the lab; we want to bring them to people for the benefit of humankind.

So in a nutshell, that’s what INBT is all about. To learn more about some of our specific programs and about some of the other centers we have launched under the INBT “brand”, read the other articles in this series. You can also watch this video about INBT. 

This article is part of a series of brief reports on INBT and its different components and programs. Together, we hope these articles will help readers inside and outside of the Johns Hopkins University community to understand what INBT is and what we do.

 

My life as an undergraduate researcher

I joined the Denis Wirtz Lab in the Institute for NanoBioTechnology the summer after my freshman year. I was nervous to start in a lab with such brilliant scientists, but everyone was really welcoming and friendly. After observing graduate students and postdoctoral fellows in the lab, I was given my own project. I had free rein to design the protocol and figure out how to analyze the data.

Katherine Tschudi. (Photo by Mary Spiro)

Katherine Tschudi. (Photo by Mary Spiro)

At first, it was difficult, but working through this and the inevitable obstacles that came made me a better researcher and scientist. I am incredibly grateful for this experience as a senior as I look back and see how the Wirtz Lab has helped me grow professionally and academically.

As a Chemical and Biomolecular Engineering major at Hopkins, we study how different physical, chemical, and biological processes work. In Wirtz Lab, I have had the opportunity to see this in action. Through my two years, I’ve looked at the differences in cell proliferation and motility for metastatic and primary cancer cells. I learned how to ask the right questions, how to think critically about data, and how to solve problems. Using the skills from Wirtz Lab, I also had the amazing opportunity to research abroad in Switzerland at the École Polytechnique Fédérale de Lausanne.

In February 2014, I will be starting a job at Genentech, and I give a lot of credit to the great undergraduate research experience I’ve had in INBT. If you want to read more about my research experiences, I wrote a blog for Hopkins Admissions during my years at Hopkins and have around six posts detailing my experience.

Click here to read Kate’s six blog entires about working in the Wirtz Lab at Hopkins-Interactive.

Kate Tschudi earned her degree in Chemical and Biomolecular Engineering in December 2013. She is just one of the many undergraduate students who have benefitted by participating in undergraduate research in an INBT affiliated laboratory. Johns Hopkins University, founded as a research institute, emphasizes undergraduate research experiences, and more than half of the undergraduates participate in research projects at some point during their academic careers here.  Johns Hopkins Institute for NanoBioTechnology actively supports undergraduate research opportunities and in an informal way helps match students to projects in laboratories of affiliated faculty members. 

Related Links:

Wirtz Lab

 

Studying cells in 3D, the way it should be

When scientists experiment on cells in a flat Petri dish, it’s more been a matter of convenience than anything that recapitulates what that cell experiences in real life. Johns Hopkins professor Denis Wirtz for some time has been growing and studying cells three dimensions, rather than the traditional two dimensions. And pretty much, he’s discovered that a lot of what we think we know about cells is dead wrong.

cancer-in-3d-impact_0

Cell in 3D. Image by Anjil Giri/Wirtz Lab

In this recent article by Johns Hopkins writer Dale Keiger, you will discover what Wirtz has discovered through his investigations. Furthermore, you will find out about the man behind these revolutionary ideas that are turning basic cell biology upside-down, as well as challenge a lot of what we thought we understood about diseases like cancer.

Wirtz directs the Johns Hopkins Physical-Sciences Oncology Center and is associate director and co-founder of Johns Hopkins Institute for NanoBioTechnology. He recently launched the Center for Digital Pathology. He is a the Theophilus Halley Smoot professor of chemical and biomolecular engineering.

You can read the entire magazine article “Moving cancer research out of the Petri dish and into the third dimension” online here at the JHU Hub.