Making Old Bones New Again PDF Print E-mail
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Friday, 01 August 2014 08:03

New Study Offers Insight Into Strengthening Bones Made Fragile by Age, Diabetes, and Osteoporosis

As we age, our bones grow more brittle and more susceptible to fracture. Individuals with diabetes or with certain types of osteoporosis often are similarly afflicted with brittle bones. A new study from biomedical engineers at Rensselaer Polytechnic Institute demonstrates how the compound N-phenacylthiazolium bromide, or PTB, dissolves the sugary impurities within bone tissue that cause our femurs, fibulas, and other bones to become more fragile. Using PTB to reduce bone fragility and boost bone flexibility could lead to new strategies for preventing bone fractures in elderly individuals, as well as accelerated bone healing in patients with diabetes or osteoporosis. “This study opens the door to new ways of thinking about the well-established, highly serious problem of brittle bones,” said Deepak Vashishth, professor in the Department of Biomedical Engineering and director of the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer, who led the study. “These research findings are an important milestone on the path to our long-term goal of realizing a drug-based intervention for reducing age-related changes in bone tissue.” Results of the study, titled “N-Phenacylthiazolium Bromide Reduces Bone Fragility Induced by Nonenzymatic Glycation,” were published online this week by the journal PLOS ONE. See the full paper here. Rensselaer biomedical engineering graduate Brian S. Bradke, who received his undergraduate degree in 2003 and his doctoral degree earlier this year, was co-author of the paper with Vashishth. Bones are constantly being remodeled within the human body. Cells produce acids and proteases to break down minerals and proteins in the bone, which are then resorbed into the body. At the same time, to compensate for the resorbed tissue, bones are fortified through chemical deposition and mineralization. This ongoing remodeling process slows down as cells are unable to fully remove bone containing sugary impurities called advanced glycation end-products, or AGEs, which form naturally in proteins. AGEs can modify surrounding tissue, rendering bone proteins unable to be resorbed back into the body. Over time, this leads to the bone becoming increasingly more fragile. Bone remodeling slows with age, meaning AGEs accumulate at a great rate as we grow older. Individuals with diabetes, certain types of osteoporosis, or metabolic bone diseases are also known to have above-average AGE content. Higher concentrations of AGEs make these groups more susceptible to bone fracture and longer healing time for bone injuries. “Once proteins in bone are modified, or cross-linked, they can no longer be digested by protease or resorbed by the body,” Vashishth said. “When this happens, the affected bones essentially freeze in time, unable to regenerate. This is a huge problem.” The chemical PTB has previously been shown to be effective for dissolving AGEs and reducing stiffness in blood vessels for cardiovascular applications. Vashishth said his new study is the first to investigate the affect of PTB on bones. He and Bradke applied PTB using different methods to multiple samples of human bones, taken from nine male donors between the ages of 19 and 80. The researchers tested the strength of the bones and used fluorescence to measure the amount of AGEs in the bones. Compared to the control groups, bones treated with PTB showed a significant decrease in AGE content, as well as significant increase in flexibility, without losing calcium. The data suggests that treatment with PTB could be an effective means to reduce AGE content and decrease bone fragility caused by the modification, or cross-linking, of bone protein, Vashishth said. “We found that PTB treatment was effective across different age groups. This is important because recent research suggests reducing the AGE content of mature bone may initiate bone turnover and promote new bone formation,” he said. “Overall, we are excited to continue investigating how PTB and its derivatives may be suitable treatments for improving bone quality.” This research was funding in part by a special grant from the Whitaker Foundation and by the National Institutes of Health/National Institute of General Medical Sciences pre-doctoral training grant in biomolecular science and engineering at the Rensselaer CBIS. “Vashishth is a leader in work uncovering the molecular basis of protein glycation, which has far-reaching implications in human health, including osteoporosis and other bone degenerative diseases,” said Jonathan Dordick, vice president for research and the Howard P. Isermann Professor of Chemical and Biological Engineering at Rensselaer. “Using a biomolecular strategy to combat sugar build-up in bones, Vashishth and Bradke identified a direct and tantalizingly simple therapeutic opportunity that could impact millions of patients.”

Last Updated on Friday, 01 August 2014 09:29
 
Peter Tessier Named Richard Baruch Professor at Rensselaer Polytechnic Institute PDF Print E-mail
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Monday, 28 July 2014 12:10

Troy, N.Y. – Protein engineering expert Peter Tessier has been named the Richard Baruch M.D. Career Development Professor at Rensselaer Polytechnic Institute. An endowed professorship is among the highest honors bestowed on a Rensselaer faculty member.

“We congratulate Dr. Tessier on his appointment as the Richard Baruch M.D. Career Development Professor,” said Shekhar Garde, dean of the School of Engineering at Rensselaer. “Pete is an outstanding researcher and a gifted mentor. In the laboratory, his work is pushing the frontiers of protein engineering toward fighting devastating diseases and addressing human health and quality of life. In the classroom, he challenges and inspires students, hastening them along their path to becoming the technological leaders of tomorrow.”

The Richard Baruch M.D. Career Development Professor is supported by an endowment established in 2002 by Johanna and Thomas R. Baruch ’60 to recognize “those promising young faculty members who aspire to achieve their personal best.” Thomas Baruch, who named the chair in honor of his father, serves as a member of the Institute Board of Trustees. The Baruchs have also been generous supporters of Rensselaer and are members of the Stephen Van Rensselaer Society of Patroons.

Tessier is an associate professor in the Department of Chemical and Biological Engineering and a member of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer. He joined the Rensselaer faculty as an assistant professor in 2007 following a postdoctoral fellowship at the Massachusetts Institute of Technology’s Whitehead Institute for Biomedical Research. He was named an associate professor in 2013.

Tessier’s research focuses on designing, developing, and optimizing a class of large therapeutic proteins, or antibodies, that hold great potential for detecting and treating human disorders ranging from cancer to Alzheimer’s disease. His research interests include designing antibodies for detecting and treating Parkinson’s and others diseases, redesigning therapeutic antibodies to increase their stability and efficacy, and identifying and optimizing small molecule compounds to inhibit toxic protein aggregation associated with Alzheimer’s disease.

This work has been recognized with a number of awards. In 2010, Tessier received the Pew Scholar Award in Biomedical Sciences, as well as a Faculty Early Career Development Award (CAREER) from the National Science Foundation. In 2012, he received a Rensselaer Early Career Award and the Rensselaer School of Engineering Research Excellence Award. In 2014, he received an Alexander von Humboldt Fellowship to support his research at the Max Planck Institute of Biochemistry in Martinsried, Germany.

Tessier received his bachelor’s degree in chemical engineering from the University of Maine, and his doctoral degree in chemical engineering from the University of Delaware.

- See more at: http://news.rpi.edu/content/2014/07/23/peter-tessier-named-richard-baruch-professor#sthash.i8TO52uI.dpuf

Last Updated on Monday, 28 July 2014 14:42
 
Rensselaer Polytechnic Institute Researchers Develop New Method of Fatty Acid Production Via Dynamic Regulation PDF Print E-mail
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Monday, 28 July 2014 12:03

Technique Has Applications for Medicine, Biofuel, and Commodity Chemical Production

Troy, N.Y. – A team of Rensselaer Polytechnic Institute researchers led by metabolic engineer Mattheos Koffas has developed a technique to more efficiently produce large quantities of the fatty acids that form the basis of compounds used in biofuels, medicine, and commodity chemical production.

Results of the study conducted by Koffas and his research group in the Center for Biotechnology and Interdisciplinary Studies over the past two years are detailed in a paper called “Improving fatty acids production by engineering dynamic pathway regulation and metabolic control,” which was published online this week by the Proceedings of the National Academy of Sciences. Click here to read the full paper. The research was supported by the National Science Foundation.

Koffas and his team developed a sensor that manipulates in real time two cellular pathways that regulate production of malonyl-CoA, which is the limiting precursor in fatty acid production. By utilizing the sensor-based dynamic regulation technique at the cellular level, the researchers were able to maximize production of malonyl-CoA while minimizing damage to the cell.

The fatty acids produced by this technique are essentially identical to those produced naturally by plants and microorganisms and are used as the basis of biofuels and chemical compounds used in medicine and industry. “In order for these fatty acids to be used in biofuel, for example, we need techniques to produce them inexpensively and in huge quantities,” Koffas said.

Previous efforts to produce fatty acids relied on static regulation – turning genes on or off entirely – rather than dynamic regulation.

“We have basically developed a sensor that can sense the state of the cell and, based on the state of the cell, can decide which genes need to be ‘upregulated,’ so we increase their transcription, and which genes need to be ‘downregulated,’ so we turn down their transcription levels,” Koffas said.

Koffas’ team created the sensor by harnessing two promoters that behave in opposite manners within the cell and combining their behaviors to create a “switch.” One of the promoters turns off malonyl-CoA biosynthesis when it senses a build-up in the cell, the other turns on malonyl-CoA production when it senses a scarcity in the cell.

“The switch controls both the sink pathway and the source pathway simultaneously to control how much malonyl-CoA is produced,” Koffas said. “This dynamic regulation opens up new venues to optimize production of malonyl-CoA-derived compounds.”

The concept of a sensor that controls cellular chemical production has implications beyond fatty acids. “Potentially this sensor can be used for improving yields for other chemicals of commercial interest,” Koffas said.

Koffas is the Career Development Associate Professor in the Department of Chemical and Biological Engineering. He was joined in this research by Rensselaer research associate professor Fuming Zhang, research assistant professor Linguyn Li, graduate student Peng Xu, and Gregory Stephanopoulos, a chemical engineering professor at the Massachusetts Institute of Technology.

- See more at: http://news.rpi.edu/content/2014/07/22/researchers-develop-new-method-fatty-acid-production#sthash.jmWeMypS.dpuf

Last Updated on Monday, 28 July 2014 15:30
 
RPI In The News: Q&A with Shekhar Garde PDF Print E-mail
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Monday, 28 July 2014 12:00

Shekhar Garde is an Indian-born chemical engineer at Rensselaer Polytechnic Institute. He studies the role of water in the creation of life and is a pioneer in animating molecular dynamics, producing a 3-D Imax film called “Molecules to the Max.”

READING Currently, I am rereading “Perfectly Reasonable Deviations From the Beaten Track,” a chronological collection of the letters by one of my favorite scientists, Richard Feynman. The letters are from when he was young to when he was a Nobel Prize winner and so on. He responds to famous scientists of the time but then also to cranks writing to him about why they don’t regain the energy expended going upstairs when they go back downstairs. They open a unique window into the amazingly curious, refreshing, articulate, funny and intelligent character that Feynman was.

I recently finished reading “Sceptical Essays,” by Bertrand Russell. Russell’s logic is crystal clear and many of the topics he discusses, from education of children to the role of authority, seem to me to be highly relevant in the modern times.

Photo

Credit Rensselaer Polytechnic Institute

 

LISTENING “This American Life” podcasts. My favorite episodes are “Invention of Money,” “Fiasco” and the little piece by Spalding Gray on taking ski lessons in his 60s.

Also, Indian classical music is frequently on in our home. I play an Indian classical bamboo flute. And my wife and one of my daughters take vocal lessons over Skype from my high school classmate back in India, so I get to hear the ragas they are learning. This prompts me to play the same ragas by my favorite singers, Bhimsen Joshi or Kaushiki Chakrabarty. Ragas use only certain notes and develop into beautiful compositions starting slow and then taking speed.

WATCHING I am perfectly happy to lose myself watching whatever my two daughters are watching on the computer. I loved “A Cat in Paris.” It’s a French cartoon with no dialogue. It’s beautiful and very different animation than Disney, like the colors and lights coming through the windows. It’s like a piece of art.

And I recently watched Season 1 of Anthony Bourdain’s “Parts Unknown.” He’s not afraid of anything. When I go to India, I drink boiled water. But he tries everything, everywhere he goes, and tries to understand the culture and the people and the politics. It gives me the vicarious pleasure of having gone there.

FOLLOWING Having grown up in India, I can’t escape the urge to follow cricket. The website I visit every day is espncricinfo.com. The articles by the likes of Ed Smith or Ramachandra Guha on this site have given me immense pleasure.

A scientific blog that I follow with interest is called “Water in Biology” by Philip Ball, a London-based writer. Phil’s blog entries invariably point me to some interesting recent papers I may have missed.

PAINTING I recently bought a Buddha Board. It’s a gray-colored board, on which you paint with just water using a brush. The painting evaporates gradually, creating different shades, and leaving you with a fresh board after a few minutes. Whatever the deeper significance about fickleness of life, it is fun to play with it.

Last Updated on Monday, 28 July 2014 12:03
 
Professor Linda Schadler Appointed Vice Provost and Dean for Undergraduate Education PDF Print E-mail
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Tuesday, 01 July 2014 10:26

To: The Rensselaer Community
From: Shirley Ann Jackson, Ph.D.
President
Professor of Physics
Professor of Engineering Sciences
Date: July 1, 2014
Re: Professor Linda Schadler Appointed Vice Provost and Dean forUndergraduate Education

It is my pleasure to announce the appointment of Dr. Linda Schadler as Vice Provost and Dean for Undergraduate Education, following a national search. Dr. Schadler, the Russell Sage Professor and Associate Dean for Academic Affairs for the School of Engineering, will assume this new role on Oct. 13, 2014.

In this position, Dr. Schadler will be responsible for overseeing the Institute's undergraduate degree programs. Along with enhancing the core curriculum and growing opportunities for undergraduate research and international experiences, she will strengthen programs focused on student advising, retention, graduation, and other student support services.

Dr. Schadler also will play an important role in the implementation of Clustered Learning, Advocacy, and Support for Students (CLASS), and advancing Institute-wide initiatives in teaching and learning, such as the Mandarin Project and Art Across the Curriculum.

Our undergraduate programs, renowned for their intellectual rigor and innovative pedagogies, are at the core of the Rensselaer undergraduate experience. Dr. Schadler is a world-class researcher and a gifted academic administrator. Her passion for education is proven and palpable. As Vice Provost and Dean for Undergraduate Education, her contributions will be critical as we continue toward our bicentennial in 2024.

Following a postdoctoral researcher position at IBM Yorktown Heights, Dr. Schadler started her academic career as a faculty member at Drexel University in Philadelphia before joining Rensselaer in 1996. She was named associate professor in 1999 and full professor in 2003. In 2009 she was appointed associate dean for academic affairs for the School of Engineering, and in 2012 was named the Russell Sage Professor.

Active in materials research for over 23 years, Dr. Schadler is an experimentalist and her investigations have focused on the mechanical, electrical, and optical properties of two-phase systems, primarily polymer composites. She is the author or co-author of more than 140 journal publications, several book chapters, and one book. Additionally, Dr. Schadler is one of three leaders of the Molecularium Project, which has led to the creation of two award-winning animated movies and an award-winning educational website, all engineered to teach young children about the world of atoms and molecules.

As associate dean in the School of Engineering, Dr. Schadler led the implementation of two important new programs. In 2013, the School introduced a new "Code of Honor" to reflect and showcase its expectations for students to demonstrate the highest standards of honesty and integrity. Also last year, the School established a new Student Service Hub, a place for students to get answers to their academic services questions.

Dr. Schadler is a fellow of ASM International and a former member of the National Materials Advisory Board of the National Research Council. She received her B.S. from Cornell University and her Ph.D. from the University of Pennsylvania, both in materials science and engineering.

Please join me in congratulating Dr. Schadler as she begins the next chapter of her career at Rensselaer.

 

Last Updated on Tuesday, 01 July 2014 10:31
 
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