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The pathway, explains Rubin, is like a series of links in a chain, with enzymes facilitating reactions along the way. “We discovered that if you inhibit the very first enzyme in the chain, you inhibit everything else downstream and eventually the bacteria die,” he explains. The research group tested phenothiazine, |
a drug used in the past to treat schizophrenia, in cultures of Mycobacterium tuberculosis, the bacterium that causes TB. They found that phenothiazines killed the bacterium in culture and suppressed its growth in mice with acute TB infection. While the effect on the growth of TB in mice was small, |
it suggested that a valid target was identified. The research group went on to show that the enzyme disabled by the phenothiazines is called type II NADH dehydrogenase and is a unique and important antimicrobial target. “What we have now is a new target in TB,” says Rubin. “We’ve been |
able to find at least the beginnings of a class of compounds that we can start working with and that we know is biochemically active against the TB bacteria in culture and in small animals.” Is it a new drug for tuberculosis? Not yet, cautions Rubin. It’s premature to say |
that this class of drugs will cure TB, but it does represent the start of basic research towards that, he concludes. Next steps include more investigations on inhibitors of the NADH biochemical pathway in TB, and the development of high-throughput screens to find better and safer inhibitors of type II |
NADH dehydrogenase. This work was supported by grants from the National Institutes of Health. Rubin and Weinstein’s coauthors are Takahiro Yano, Lin-Sheng Li, David Avarbock, Andrew Avarbock and Douglas Helm from Penn, and Andrew McColm, Ken Duncan, and John T. Lonsdale from GlaxoSmithKline (Collegeville, PA and Steven... |
were conducted at GlaxoSmithKline. Penn researchers report no conflicts of interest. PENN Medicine is a $2.7 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded... |
of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic Penn Health System is comprised of: its flagship hospital, the Hospi... |
Pennsylvania, consistently rated one of the nation’s “Honor Roll” hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation's first hospital; Presbyterian Medical Center; a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home health care and hospice. |
Anthony Atala is a surgeon, the Chair of the Department of Urology at the Wake Forest University for Medicine, and the Director of the Wake Forest Institute for Regenerative Medicine, where he specializes in the growth and regeneration of organs and tissues. He is also the former Director of the |
Laboratory for Tissue Engineering and Cellular Therapeutics at Children's Hospital Boston. When Atala joined the Wake Forest Institute for Regenerative Medicine in 2004, he led the research team that created the first lab-grown organ - a human bladder - to be successfully implanted in a human being. Currently, he is |
working on growing and printing other organs to eventually reduce the time that transplant patients spend waiting for an organ. He and his team have successfully printed prototype kidneys for this purpose. Atala has also been successful in harvesting stem cells from the amniotic fluid of pregnant women. Amniotic stem |
cells can be manipulated to transform into various types of mature cells that make up nerves, muscles, bones and other tissues. These stem cells are able to thrive for years and can be used to grow new tissues and organs when damaged ones are in need of replacement. They are |
easier to grow than embryonic stem cells and avoid the ethical concerns that are associated with embryonic stem cell research. Atala believes that, "A bank of 100,000 specimens of the amniotic stem cells theoretically could supply 99% of the US population with perfect genetic matches for transplants." Atala's lecture w... |
address the implications of organ and tissue regeneration, as well as consider what the future of synthetic organs will bring. ABOUT THIS LECTURE Today there are many more people awaiting organs than there are organs available from donors. People are dying as a result. And the problem is only going |
to get worse in the future as the number of organs required grows at a much faster rate than the number of donors. Dr. Anthony Atala, a leading researcher in the field of regenerative medicine, is exploring a variety of approaches to making human organs in the lab for transplant |
into those with failing organs. In this presentation, he will discuss where the field of regenerative medicine is going in the context of the approaches that he is exploring. Possibly the most intriguing of these is the use of a device that his lab has built based on the principle |
of an ink-jet printer. Instead of ink in the printer that he has built, Atala uses human cells and he quite literally prints human organs. To do so, he extracts cells from the patient and, using the extracted cells as seeds, grows many more in the lab. He then mixes |
the cells with a chemical that turns into a gel when it comes into contact with water. He places this mixture in the 'ink' cartridge of the printer that he has built. The ink-jet mechanism of the printer prints a layer of cells onto a petri dish containing water, which |
with the chemical additive, turns the water into a gel. The dish is then moved down a fraction of an inch and a second layer is printed. This continues until the organ is complete. The printing process is designed in such a way that the cells are able to create |
various shapes in each layer. In this way, Atala is able to create blood vessels and other essential organ components as he prints it such that once complete he has a functioning organ. Furthermore, because the organ has been made with the patient's cells this approach avoids problems of rejection |
associated with donor supplied organs. At this time, printed organs have not been used in humans; Atala is still developing the technique and significant work remains before the approach is ready for to be tested in patients. Previous to the printing of organs, Atala has artificially grown organs using human |
tissue. For example, he was the first to successfully create a bladder in the laboratory and place it into a human. Anthony Atala's Profile Anthony Atala's profile on the Wake Forest Institute for Regenerative Medicine website Anthony Atala's TED Talk on lab-grown organs Anthony Atala's TED Talk on printing a |
Hormone Promises to Keep Joint Injuries from Causing Long-term Osteoarthritis Goal to Extend Useful Life of Arthritic Knees and Hips September 12, 2009 An existing osteoporosis drug is the first |
ever found to prevent cartilage loss from osteoarthritis following injury to a joint, and may also regenerate some cartilage that has been lost to osteoarthritis, according to an early study |
presented today at the annual meeting of the American Society for Bone and Mineral Research in Denver. While the study was in mice, the model closely mimics human osteoarthritis that |
develops following knee injuries, according to the study authors. Cartilage can become damaged by many kinds of injury and by mechanical stresses that come with age. Over time, damaged cartilage |
deteriorates to cause osteoarthritis (OA), with its attendant joint inflammation and pain. Currently available drugs like steroids or non-steroidal anti-inflammatory agents (e.g. Advil, Aleve) reduce pain but do not address |
the loss of cartilage behind the osteoarthritis, which is projected to afflict more than 50 million Americans by 2020. Cartilage forms the sponge-like, shock-absorbing layers that keep the impact of |
running and jumping and lifting from grinding bones against each other in joints. The cell type at the heart of osteoarthritis is the chondrocyte, the cartilage-producing cell responsible for maintaining |
the integrity of joint cartilage. Outside of joints, chondrocytes undergo a normal maturation process that helps to form bone as part of fracture healing and bone growth in children. Disease |
processes and injury, however, cause chondrocytes in joint surface cartilage to become like those that help to heal bone elsewhere, but where bone is not supposed to form. This mistaken |
maturation contributes to the gradual destruction of the joint seen in osteoarthritis. Parathyroid hormone (PTH), known as teriparatide in drug form, has emerged as a major player in the maintenance |
and healing of bone, and the race is on to design new applications for it. Past studies have established that PTH prevents chondrocytes from undergoing maturation, and stimulates their proliferation, |
preserving larger pools of cartilage cells in the joint. Signaling molecules like PTH have their effect in the body by interacting with specifically shaped proteins on the cell surfaces called |
receptors. PTH docks into its receptors, like a ship coming into port, which changes the shape of the dock such that biochemical signals are sent. The authors of the current |
study observed that chondrocytes within injured and degenerating cartilage have more PTH type 1 receptors on their surfaces. This makes them especially sensitive to the PTH signal that prevents harmful |
chondrocyte maturation into bone in the joint cartilage. Thus, PTH therapy should increase the cartilage supply exactly where cartilage loss is causing disease. “Right now physicians have no way to |
bring back cartilage in patients who have lost it to osteoarthritis,” said Randy Rosier, M.D., Ph.D., professor within the Department of Orthopaedics and Rehabilitation at the University of Rochester Medical |
Center. “Our current results, at least in mice, show that we can inhibit cartilage degeneration and improve the volume of cartilage in diseased joints. It’s remarkable enough that this compound |
delays the loss of cartilage, but these results show it also may be able to restore, at least to some extent, cartilage in already degraded joint surfaces.” Researchers examined the |
impact of a daily dose of Forteo®/teriparatide, manufactured by Eli Lilly, and a generic version of teriparatide made by Sigma on the progress of OA following injury in study mice. |
Experiments established a five-fold increase in PTH type 1 receptor expression in the articular cartilage of mice with injury-related osteoarthritis when compared to healthy cartilage. Injury triggers genetic mechanisms in |
an attempt to begin repairs, a response that may be responsible for the increase in PTH receptor in the joint. This in turn makes damaged cartilage particularly responsive to PTH. |
In the current study, one group of mice with cartilage and ligament injuries was randomized to receive either saline as a control, Forteo® or generic PTH daily for 12 weeks. |
A second group of mice with joint injuries did not receive treatment until 8 weeks after injury. The delay was an attempt to determine the effect of treatment once the |
osteoarthritic process was already underway and some cartilage lost, a scenario that more closely mimics clinical reality. Injurd patients do not ask their doctor to prevent the onset of osteoarthritis |
10 years in the future, Rosier said. They come in when an old injury and time have combined to degrade cartilage to the point where function is lost and pain |
felt. Studies revealed that after 12 weeks of Forteo®- or generic PTH treatment, there was approximately 27 percent more joint cartilage compared to saline-treated mice. Strikingly, delayed teriparatide treatment was |
even more effective in improving the amount of cartilage, with up to 35 percent more cartilage in Forteo®- and PTH-treated groups than in the saline group, suggesting an ability to |
regenerate at least some of the lost cartilage. With a new use patent application in place, the team will next seek to confirm the durability of the effect in further |
animal studies, and prepare to seek funding from the National Institutes of Health to begin pilot clinical studies of PTH treatment of osteoarthritis in humans, possibly in the later half |
of 2010. Along with Rosier, the study was led by Erik Sampson, Todd O’Brien, Di Chen, Susan Bukata, J. Edward Puzas, Regis O’Keefe and Michael Zuscik within the Department of |
Orthopaedics and by Hani Awad in the Department of Biomedical Engineering at the University of Rochester Medical Center. The study was funded by the National Institutes of Health. “These pre-clinical |
findings provide strong proof-of-concept support for the potential use of teriparatide to slow joint cartilage degeneration in OA patients, and perhaps even reverse it,” Rosier said. “In the near future, |
we hope this serves as the foundation of new treatments that restore function to long-injured joints, perhaps staving off joint replacement surgeries for some years.” Note: Drs. Puzas and Bukata |
|Dr. Elizabeth Cochran, a geophysicist with USGS, conducts seismic research along the San Andreas Fault in California.| Dr. Elizabeth Cochran, a geophysicist with the U.S. Geological Survey, was named one of President Obama’s recipients of the Presidential Early Career Awards |
for Scientists and Engineers, the highest honor bestowed by the United States government on science and engineering professionals in the early stages of their independent research careers. Cochran, who came to work for the USGS in June after a career |
as an assistant professor at the University of California, Riverside, is an accomplished seismologist. She has made important contributions to the understanding of earthquake physics and earthquake triggering, the physical properties and geometry of earthquake fault zones and their evolution |
after earthquakes, and to the development of a new method of earthquake monitoring using low-cost earthquake sensors, called the Quake-Catcher Network (QCN). This network allows scientists to monitor earthquakes and quantify ground shaking with unprecedented spatial resolution through data gathered |
from citizen volunteers. “It is inspiring to see the innovative work being done by these scientists and engineers as they ramp up their careers — careers that I know will be not only personally rewarding but also invaluable to the |
Nation,” President Obama said. “That so many of them are also devoting time to mentoring and other forms of community service speaks volumes about their potential for leadership, not only as scientists but as model citizens.” The Presidential early career |
awards embody the high priority the Obama Administration places on producing outstanding scientists and engineers to advance the Nation’s goals, tackle grand challenges, and contribute to the American economy. “It is an incredible honor to receive this award, and it |
is nice that it recognizes the combination of research and education,” said Cochran, who was nominated for the award by the National Science Foundation. “I am very proud and a little stunned.” “Dr. Cochran’s work on next generation sensor networks |
is exactly what the United States needs to help enable earthquake early warning,” said USGS Director Dr. Marcia McNutt. “As was clearly demonstrated by the recent Japanese experience, even a few seconds of warning before an earthquake can reduce the |
loss of life and property. Dr. Cochran’s innovative research will help make the nation safer from this natural hazard.” The QCN, a collaborative research project between Cochran and Jesse Lawrence of Stanford University, uses computers that are installed with software |
and special sensors to record moderate-to-large earthquakes and aftershocks. Citizen volunteers have the sensors installed externally to their desktop computers or internally to their laptop computers. These computers become seismic stations by providing the physical infrastructure, computer, internet connection, power... |
and the location and measurement of seismic activity. The computers are then networked using distributed computing techniques that allow scientists to monitor the sensors and retrieve earthquake data automatically. “The Quake-Catcher Network is a way to involve the public in |
scientific data collection in high-risk earthquake and aftershock zones in the United States and around the world and to collect seismic data in non-traditional ways,” said Cochran. |Dr. Elizabeth Cochran.| By using this sensor-driven process, a great number of seismic |
data can be processed in a short period of time and produce nearly instantaneous detection and characterization of earthquakes. The first release of the software was in Reno, Nev., in April 2008. A few people from the area signed up |
to get the software, just in time to record a swarm of earthquakes that hit in June of that year. “When the swarm of earthquakes struck Reno, the information from these citizen volunteers enabled us to test our system, and |
from that, we learned that the sensors and data communication were working correctly,” said Cochran. “For this set of earthquakes, we had some of the closest seismic stations to the swarm. We had records of those earthquakes that looked like |
typical seismograms. I was really excited that it worked. It was really fun.” Since then, volunteers have popped up in just about every state in the United States and across the world. After the magnitude 8.8 earthquake struck Chile in |
early 2010, Cochran and her team enlisted 100 volunteers in Chile to hook up the sensors to their computers. When the aftershocks kept occurring, the instrumentation provided invaluable information to scientists and proved the value of the QCN. “In the |
case of Chile, we could get estimates of magnitude and locations in about 20 to 30 seconds after earthquake started,” said Cochran. “We found we can actually do well recording earthquakes this way, and eventually we hope this is a |
way to augment existing seismic networks to provide more precise early earthquake warning.” The data Cochran and her team gathered from Chile was especially valuable in analyzing small scale ground shaking — how it is different in one location versus |
a half a mile away. “There is a lot of variation in ground shaking, even in small scales,” said Cochran. “We were able to generate our own Quake-Catcher Network ShakeMaps, or what seismologists call microzonation, where you can examine specific |
areas for earthquake hazards. This information can provide critical data to feed back into building codes and to help determine where critical infrastructure such as power plants, hospitals, water lines and transportation facilities should be built.” When the magnitude 7.0 |
earthquake struck New Zealand in September 2010, Cochran and her team deployed 180 sensors in the area. A paper on the results of the data is expected out this fall. “We are in the middle of demonstrating that the data |
from these sensor stations in New Zealand show the same amplitude and waveform characteristics as do other strong motion sensors in the area and is sufficient enough quality to produce reliable results,” said Cochran. In early September 2011, Cochran and |
her team set out on an ambitious goal: to install 500 sensor stations in the San Francisco Bay area, a high-risk earthquake location. Volunteers need to have a high speed Internet connection; a computer, about 5 years old or less |
that runs on a Windows or Macintosh operating system with a spare USB port to which the sensor can be connected; and, a small space about the size of a post-it note for mounting the sensor. Information for those interested |
in volunteering or learning more about the QCN is available online. “I came up with the idea for the Quake-Catcher Network by playing around on a Mac laptop, and my husband pointed out that you could download a widget that |
would allow you to see the real-time output from the sensor,” said Cochran. “I downloaded the widget and was seeing output from tapping I was doing on the computer, and it dawned on me that if it picked up this |
movement, it would probably pick up earthquake movements. I also knew about distributed computing that allows people to donate their unused CPU processing time to scientific projects and thought that combining the low cost sensors with distributed computing would be |
a perfect way to gather data from moderate to large earthquakes at very little cost. I discussed it with my colleague Jesse Lawrence who said, ‘That’s the coolest idea I ever heard,’ and then we pursued and received a grant |
from the National Science Foundation to start it up.” Cochran’s research is fundamental to the mission of the USGS to continue to innovate the recording of weak and strong ground motions necessary to accurately locate earthquakes, to study their rupture |
process, and to map the variations in the strong ground motions caused by the local soil conditions and the details of the earthquake rupture process. “I am really excited that the Quake-Catcher Network is moving forward and has continued to |
be successful,” said Cochran. Since its inception in 2008, the QCN has gained academic partners from the University of California-Berkeley, California Institute of Technology, University of California-San Diego and the University of Delaware. After receiving her PhD in geophysics and |
space physics from UCLA in 2005, Cochran served as a postdoctoral fellow at the Scripps Institution of Oceanography until the end of 2006, when she joined UC Riverside in 2007 as an assistant professor in earth sciences, supervising both graduate |
students and postdoctoral scholars. She joined the USGS in June 2011. Her accomplishments have been recognized by her receiving the NSF Faculty Early Career Development (CAREER) Award in 2010 and the Geological Society of America Subaru Outstanding Woman in Science |
in 2006 for the scientific impact of her work on the geosciences. She is the author or co-author of 21 peer-reviewed journal publications, 9 as a first author, and has a Scopus H-index of 7. Her first-author papers have been |
published in prestigious journals Science, Journal of Geophysical Research, Geophysical Research Letters, Bulletin of the Seismological Society of America, Seismological Research Letters, and Geology. She has also played prominent roles in professional organizations, including as the co-chair of the seismology |
discipline for the Southern California Earthquake Center since 2009 and as a member of the IRIS Data Management System Standing Committee from 2008 to 2010. The Presidential Early Career Awards for Scientists and Engineers was established by President Clinton in |
1996 and are coordinated by the Office of Science and Technology Policy within the Executive Office of the President. Awardees are selected for their pursuit of innovative research at the frontiers of science and technology and their commitment to community |
elcome to historic Germantown! George Washington and the capital were here in 1793. During the Revolution, the Battle of Germantown was fought up and down the main street, with muskets firing from house windows. The first American Bible was published here, and the first kidnapping in the United States also took place i... |
painter Gilbert Stuart worked in a small barn in Germantown. merica's history lies in the cobblestones of Germantown Avenue, echoes through the halls of Stenton and Cliveden, and is forever captured in Germantown's historic buildings, homes, and cemeteries. An incredible amount of history took place in the distance of ... |
industrial town in the end of the 19th and beginning of the 20th centuries. Then in the 1940's and 50's the area's affluent citizens began to leave for the suburbs. Today, Germantown is undoubtedly a very urbanized region; however, the historical sites have been very well preserved by the active Historical Society and ... |
Born to a Jewish father and a Catholic mother, Otto grew up in a city well known for its musical tradition. The younger of two children, Otto began studying the piano at age 10. After entering the Vienna Conservatory of Music, he gave his first concert at age 14. Encouraged by Maestro Bruno Walter, he hoped to become a... |
After Germany annexed Austria in March 1938, Otto was kicked out of the Vienna Conservatory. One night, two men ordered him to go with them to a cellar, where they forced other people to mop and scrub. They told Otto to wait his turn, but in the confusion he escaped. To get out of Austria, he entered a piano contest in... |
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