Chemical and biomolecular engineer Denis Wirtz named Smoot professor

Denis Wirtz. Photo by Will Kirk/JHU

Denis Wirtz. Photo by Will Kirk/JHU

Denis Wirtz, Johns Hopkins University professor of chemical and biomolecular engineering and director of the Engineering in Oncology Center, has been named the Theophilus Halley Smoot Professor in the Whiting School of Engineering. University president Ronald J. Daniels and the Board of Trustees determined the recipient.

Wirtz is the founding associate director of the Johns Hopkins Institute for NanoBioTechnology. He was recently named a 2009 fellow of the American Academy for the Advancement of Science in the Engineering Section for his contributions to cell micromechanics, cell adhesion, and for the development and application of particle tracking methods that probe the micromechanical properties of living cells.

He is on the Editorial Boards of Biophysical Journal, Cell Adhesion and Migration and J. Nanomedicine. In 2005, he was named a fellow of the American Institute for Medical and Biological Engineering. Wirtz won the National Science Foundation Career Award in 1996 and the Whitaker Foundation Biomedical Engineering Foundation Award in 1997.

Wirtz came to Johns Hopkins faculty in 1994 and completing a postdoctoral fellowship in Physics and Biophysics at ESPCI (ParisTech). Wirtz earned his PhD in Chemical Engineering from Stanford University in 1993.

An announcement from the Whiting School’s dean Nick Jones stated that, “Throughout his time at Johns Hopkins, Denis has distinguished himself as an outstanding scholar and teacher. Additionally, Denis’ role as a catalyst for interdisciplinary research and collaboration at the university has proven extremely effective, both in terms of the research he conducts and the support he has attracted over the years. I am confident that his current research into the physical basis for cell adhesion and de-adhesion will prove critical to our understanding of the metastasis of cancer and enable important breakthroughs in the diagnosis and treatment of cancer in the years to come.”

The Smoot Professorship was established in 1981 through the estate of Theophilus H. Smoot, who joined Johns Hopkins as a research assistant in the Department of Mechanical Engineering in 1942 and later a research associate in the department in 1946. Upon the passing of Mr. Smoot in 1976 and his widow, Helen A. Smoot in 1980, the Theophilus Halley Smoot Fund for Engineering Science was created.  The first Smoot Professorship was awarded in 1981 to Stanley Corrsin, a professor and former chair in the department of mechanical engineering. Robert E. Green, Jr., professor in the department of materials science, held the professorship from 1988 through 2007.

Presentation of the Smoot professorship will occur in the spring.

Wirtz Lab

Named Professorships of The Johns Hopkins University

Johns Hopkins Institute for NanoBioTechnology

Johns Hopkins Engineering in Oncology Center

Story by Mary Spiro and from materials provided by the Whiting School of Engineering.

INBT, EOC directors named AAAS 2009 Fellows

The Johns Hopkins Whiting School of Engineering faculty members who direct the Institute for NanoBioTechnology and Engineering in Oncology Center both have been awarded the distinction of AAAS Fellow. Election as a Fellow is an honor bestowed upon AAAS members by their peers.

Peter Searson, INBT director. Photo by Will Kirk/JHU

Peter Searson, INBT director. Photo by Will Kirk/JHU

Denis Wirtz, EOC director. Photo by Will Kirk/JHU

Denis Wirtz, EOC director. Photo by Will Kirk/JHU

Peter C. Searson, the Joseph R. and Lynn C. Reynolds Professor of Materials Science and Engineering, was named for distinguished contributions to the field of surface chemistry and nanoscience. His research interests include surface and molecular engineering, and semiconductor quantum dots.

Searson directs the interdivisional Institute for NanoBioTechnology launched in May 2006, which brings together researchers from medicine, engineering, the sciences, and public health to create new knowledge and develop new technologies to revolutionize health care and medicine. INBT currently has more than 190 affiliated faculty members. Searson has secondary appointments in the Krieger School of Arts and Sciences Department of Physics and Astronomy and the Johns Hopkins School of Medicine Department of Oncology.

Denis Wirtz, the Theophilus H. Smoot Professor of Chemical and Biomolecular Engineering, was elected for his contributions to cell micromechanics and cell adhesion. He also was distinguished for his development and application for particle tracking methods to probe the micromechanical properties of living cells in normal conditions and disease state. Wirtz studies the biophysical properties of healthy and diseased cells, including interactions between adjacent cells and the role of cellular architecture on nuclear shape and gene expression.

Wirtz directs the newly formed Johns Hopkins Engineering in Oncology Center. The EOC is a Physical Sciences in Oncology program center of the National Cancer Institute launched in October 2009 with a $14.8 million grant from the National Institutes of Health. EOC brings together experts in cancer biology, molecular and cellular biophysics, applied mathematics, materials science, and physics to study and model cellular mobility and the assorted biophysical forces involved in the spread of cancer. Wirtz also serves as co-director of the Institute for NanoBioTechnology and has a joint appointment in the Johns Hopkins School of Medicine Department of Oncology.

A total of seven Johns Hopkins faculty members were elected to AAAS this year. Read about all of them in a Johns Hopkins University press release listed in the links below.

This year 531 members have been awarded this honor by AAAS because of their scientifically or socially distinguished efforts to advance science or its applications. New Fellows will be presented with an official certificate and a gold and blue (representing science and engineering, respectively) rosette pin on Feb. 20 at the AAAS Fellows Forum during the 2010 AAAS Annual Meeting in San Diego.  AAAS Fellows were announced in the AAAS News & Notes section of the journal Science on Dec. 18,  2009.

Story by Mary Spiro with materials provided by AAAS.

Seven Johns Hopkins Researchers Named 2009 AAAS Fellows

Searson Group Lab page

Wirtz Group Lab page

Johns Hopkins Institute for NanoBioTechnology

Whiting School of Engineering

A Perinuclear Actin Cap Regulates Shape

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Cell’s ‘cap’ of bundled fibers could yield clues to disease

Newsletter readers! If you are looking for the 2010 NanoBio Symposium story go to: http://inbt.jhu.edu/outreach/symposium
Doctoral student Shyam Khatau, left, and Denis Wirtz, director of the Johns Hopkins Engineering in Oncology Center, played a key role in finding a bundled “cap” of thread-like fibers that holds a cell’s nucleus in its proper place. Photo by Will Kirk, Homewoodphoto.jhu.edu.

Doctoral student Shyam Khatau, left, and Denis Wirtz, director of the Johns Hopkins Engineering in Oncology Center, played a key role in finding a bundled “cap” of thread-like fibers that holds a cell’s nucleus in its proper place. Photo by Will Kirk, Homewoodphoto.jhu.edu.

It turns out that wearing a cap is good for you, at least if you are a mammal cell.

Researchers from the Johns Hopkins Engineering in Oncology Center have shown that in healthy cells, a bundled “cap” of thread-like fibers holds the cell’s nucleus, its genetic storehouse, in its proper place. Understanding this cap’s influence on cell and nuclear shape, the researchers say, could provide clues to the diagnosis and treatment of diseases such as cancer, muscular dystrophy and the age-accelerating condition known as progeria.

“Under a microscope, the nucleus of a sick cell appears to bulge toward the top, while the nucleus of a healthy cell appears as a flattened disk that clings to the base,” said principal investigator Denis Wirtz, professor of chemical and biomolecular engineering and director of the Engineering in Oncology Center. “If we can figure out how and why this shape-changing occurs, we may learn how to detect, treat or perhaps even prevent some serious medical disorders.”

Scientists have known that misshapen nuclei are an indicator of disease, Wirtz said, but they were not certain how a cell controlled the shape of its nucleus, the structure in mammal cells where genetic material resides. In a study published in the Nov. 10 issue of the Proceedings of the National Academy of Sciences, however, the research team led by Wirtz reported the discovery of a fibrous structure that holds the nucleus in its place. The researchers call this new network structure the perinuclear actin cap.

“In healthy cells, the perinuclear actin cap is a domed structure of bundled filaments that sits above the nucleus, sort of like a net that is tethered all around to the perimeter of the cell membrane,”

Wirtz said. This configuration pushes the nucleus down toward the base of the cell and also creates the distinctive flattened shape of normal cells. Cells with cancer, muscular dystrophy or progeria, however, lack this distinctive cap, allowing the nucleus to float upward toward the top of the cell’s membrane. These diseased cells may appear more rounded and bulbous.

“The cap controls the shape of the nucleus by controlling the shape of the cell itself,” Wirtz said.

The perinuclear actin cap was discovered while the team was trying to find out if cell shape controls nucleus shape. By growing cells on a surface with alternating sticky and non-sticky stripes, the researchers noticed that as cells grew along a sticky stripe, their nuclei elongated as well. Using a confocal microscope — a special kind of microscope that can view an object one “slice” at a time — doctoral student Shyam Khatau was able to reconstruct the cell in three dimensions. By stacking the confocal microscope images together, Khatau, who is affiliated with the Johns Hopkins Institute for NanoBioTechnology, was able to produce short movies showing the 3-D structure of the cells, the nucleus and the perinuclear actin cap. (The movies are online here or below.)

“That’s when we saw the cap,” Khatau said, “and Dr. Wirtz realized we were on to something.”

The cap’s role in disease became evident when Khatau tested cells without the gene to produce lamin A/C, a protein found in the membrane of the nucleus of normal cells but absent in the nuclear membrane of cells from people with muscular dystrophy. Cells without lamin A/C failed to produce the perinuclear actin cap.

“We next plan to study how the cap’s effect on the shape of the nucleus affects what genes the cells express,” said Wirtz.

Khatau, who is pursuing his doctorate in the Department of Chemical and Biomolecular Engineering, is lead author of the journal article.

Additional Johns Hopkins authors on this paper are Wirtz; doctoral student Christopher M. Hale and senior Meet Patel from the Whiting School of Engineering’s  Department of Chemical and Biomolecular Engineering; and Peter C. Searson, a professor in the school’s Department of Materials Science and Engineering. Other co-authors were P. J. Stewart-Hutchinson and Didier Hodzic from the School of Medicine at the Washington University in St. Louis and Colin L. Stewart from the Institute of Medical Biology, Singapore.

This work was funded by the National Institutes of Health and the Muscular Dystrophy Association.

Story by Mary Spiro

PNAS journal article.

Johns Hopkins Engineering in Oncology Center

Johns Hopkins Institute for NanoBioTechnology

Department of Chemical and Biomolecular Engineering

Engineering in Oncology Center will probe forces that cause cancer to spread

Center director Denis Wirtz and associate director Greg Semenza

The Johns Hopkins Engineering in Oncology Center at INBT will be headed by Denis Wirtz, left. Gregg Semenza will serve as associate director. (Photo by Will Kirk/JHU)

Researchers from the Johns Hopkins Institute for NanoBioTechnology have been awarded a $14.8 million grant from the National Cancer Institute to launch a research center aimed at unraveling the physical underpinnings that drive the growth and spread of cancer. The new Johns Hopkins Engineering in Oncology Center at INBT includes 11 Johns Hopkins faculty members affiliated with the INBT and four investigators from partner universities. The project’s participants say that they hope this new line of research will lead to never-before-considered approaches to cancer therapy and diagnostics.

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

“By bringing a fresh set of eyes to the study of cancer, these new centers have great potential to advance, and sometimes challenge, accepted theories about cancer and its supportive microenvironment,” said NCI Director John E. Niederhuber. “Physical scientists think in terms of time, space, pressure, heat and evolution in ways that we hope will lead to new understandings of the multitude of forces that govern cancer, and with that understanding, we hope to develop new and innovative methods of arresting tumor growth and metastasis.”

The NCI, which is an agency of the National Institutes of Health, will allocate the Johns Hopkins-based Engineering in Oncology Center’s funding over five years. As the name of the center suggests, the researchers will look at how physical sciences play a role in the way cancer spreads, commonly called metastasis.

Wirtz, Semenza to direct EOC

Denis Wirtz, a professor of chemical and biomolecular engineering in the Whiting School of Engineering, will direct the center, and Gregg L. Semenza, a leading researcher at the School of Medicine, will serve as associate director.

“Metastasis is a highly coordinated, multistep process,” Wirtz said. “Cancer cells break free from a primary tumor, penetrate into the bloodstream, evade host defenses, stick to the interior walls of blood vessels and travel to other organs, where they set up new cancer cell colonies. During this cascade of events, tumor cells push on and are pushed by mechanical forces within their microenvironment. Cells translate those mechanical forces into biochemical signals that affect cell growth and function. If we can gain a better understanding of this process, we may find new and better ways to treat cancer.”

Wirtz, who is principal investigator, also serves as associate director of the university’s Institute for NanoBioTechnology, a cross-divisional institute launched in May 2006 with 185 Johns Hopkins faculty members who are using nanoscience to answer questions in medicine, the basic sciences and public health.

The new cancer center will similarly draw on Johns Hopkins researchers with diverse expertise to study the role of physical forces involved in the development and spread of cancer.

“Mechanical forces inside the body, such as shear exerted by blood flowing through blood vessels, typically destroy the millions of cancer cells that are constantly shed from tumors,” Wirtz said. “But the ‘fittest’ of cancer cells survive these Darwinian-like selective pressures and may become the culprits that spread cancer. Little is known about the effect of mechanical forces on the regulation of cancer cell growth. That is what the Engineering in Oncology Center and the National Cancer Institute want to find out. The results should point us to therapies and diagnostic tools that complement existing genetic or molecular treatments.”

In a congratulatory letter to Wirtz concerning the new center, Johns Hopkins President Ronald J. Daniels wrote, “This is a terrific achievement that highlights the value of interdisciplinary research and collaboration across the university, and the increasing importance this approach will have in the coming years. I am especially proud to see Johns Hopkins lead the way in this manner. … Not only will you be embarking into a new realm of scientific collaboration, you will be, at the same time, establishing Johns Hopkins as a leading center of excellence in this field. The ongoing fight against cancer demands new ideas, perspectives and approaches, and that is precisely what you are creating in [this] center.”

Semenza, the associate director, is affiliated with the School of Medicine’s departments of Pediatrics, Medicine, Oncology and Radiation Oncology, and the McKusick-Nathans Institute of Genetic Medicine. He is the C. Michael Armstrong Professor in Medicine and founding director of the Vascular Program at the school’s Institute for Cell Engineering. He also has ties to the School of Medicine’s Department of Biological Chemistry and to the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

Center will focus on three primary research aims

Semenza and Sharon Gerecht, an assistant professor of chemical and biomolecular engineering, will lead one of the center’s three key research projects related to how cancer spreads. They will focus on analyzing the makeup and physical properties of the extracellular matrix, the three-dimensional scaffold in which cells live.

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

The center’s second key research project teams Wirtz with Greg D. Longmore, a cancer cell biologist at Washington University in St. Louis. The two will study the physical basis for cancer cell adhesion and de-adhesion and how it increases the likelihood that cancer cells will break free, move into the bloodstream and migrate to other tissues. “Cancer cells are able to modulate proteins on the surface almost like a protein ‘brake’ that allows them to adhere or de-adhere in response to mechanical forces,” Wirtz said.

The center’s third primary research project will be led by Konstantinos Konstantopoulos, professor and chair of the Whiting School’s Department of Chemical and Biomolecular Engineering, and Martin L. Pomper, who holds appointments in the School of Medicine’s Department of Radiology and the Kimmel Cancer Center. These two researchers will investigate the effects of fluid mechanical forces at different oxygen tension microenvironments on tumor cell signaling, adhesion and migration.

“Fluid flow in and around tumor tissue modulates the mechanical microenvironment, including the forces acting on the cell surface and the tethering force on cell-substrate connections,” Konstantopoulos said. “Cells in the interior of a tumor mass experience a lower oxygen tension microenvironment and lower fluid velocities than those at the edges in proximity with a functional blood vessel, and are prompted to produce different biochemical signals. These differential responses affect tumor cell fate—that is, whether a cell will live or die, and whether it will be able to detach and migrate to secondary sites in the body.”

All three projects will combine experimental and computational/theoretical results to develop a better picture of how these mechanical forces influence cancer metastasis.

An educational component for graduates and postdoctoral fellows

In addition to the research component, the Engineering in Oncology Center will have a multidisciplinary training program for predoctoral students and postdoctoral fellows. The training program will be co-directed by Peter Searson, INBT’s director and the Joseph R. and Lynn C. Reynolds Professor in the Department of Materials Science and Engineering, and the School of Medicine’s Kenneth W. Kinzler, who is among the world’s most-cited cancer biologists and who serves as co-director of the Johns Hopkins Ludwig Center.

Other Johns Hopkins researchers affiliated with the Engineering in Oncology Center are Sean X. Sun, associate professor in the Department of Mechanical Engineering, and two faculty members from the Department of Biomedical Engineering: Kevin Yarema, associate professor, and Aleksander S. Popel, professor.

In addition to Longmore, the researchers from other institutions who will participate in the Johns Hopkins-based center are Timothy C. Elston, a theoretical and computational biophysicist at the University of North Carolina, Chapel Hill; Yiider Tseng, an experimental biophysicist and biochemist at the University of Florida; and Charles W. Wolgemuth, a theoretical and computational biophysicist at the University of Connecticut.

The center will incorporate two dedicated research facilities, also known as cores. The EOC Imaging Core will be established under the existing Integrated Imaging Center on the Homewood campus. J. Michael McCaffery, associate research professor of biology in the Krieger School of Arts and Sciences, will oversee the Imaging Core and facilitate imaging resources for EOC faculty. Searson will oversee the EOC Microfabrication Core, which will assist researchers in making the needed materials and devices for their experiments.

The Engineering in Oncology Center will be administered by the Institute for NanoBioTechnology, located on the Homewood campus, where research will occur in renovated laboratory facilities. Training and collaboration with investigators located at the four other research universities on the grant will occur through periodic onsite visits and via Web-based platforms.

Related Links:

National Cancer Institute’s Physical Sciences-Oncology Centers program

Johns Hopkins Engineering in Oncology Center at INBT

Johns Hopkins Institute for NanoBioTechnology