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Chemists Rationally Design Inhibitors Against an RNA Molecule that Causes Myotonic Muscular Dystrophy

by Ellen Goldbaum

Chemists at the University at Buffalo have used rational drug design to synthesize small, cell-permeable molecules that are effective in vitro against two common types of myotonic muscular dystrophy, a result that has implications for potentially curing muscular dystrophy, as well as other diseases.

The UB research was reported in two papers published in the May and July issues of ACS Chemical Biology and Journal of the American Chemical Society, respectively.

Together, the papers demonstrate that rational drug design -- where information about a target's molecular structure is used to "custom-design" potential drugs -- can greatly expedite the drug discovery process in the fight against RNA-mediated diseases, including myotonic dystrophy type 1 and type 2. There is currently no cure for these diseases, which attack muscle tissue.

Sickle cell disease, fragile X syndrome, Huntington's disease and certain forms of breast cancer are other RNA-mediated diseases.

The work is a major step forward in a multi-year effort by Matthew Disney, Ph.D., UB assistant professor of chemistry, to develop a chemical code that would enable rational design of binders to any RNA structure.

"These results demonstrate that we can build a database containing RNA structures that bind to small molecules, and use that information to potentially target any 'toxic RNA structure,' that is, any RNA structure involved in disease," says Disney, lead author on the research.

He explained that muscular dystrophy belongs to a class of diseases called triplet repeat disorders in which the genetic code has an abnormal repetition of three letters of DNA.

"The DNA with the abnormal triplet repeats is made into a defective RNA that forms an unnatural structure that binds to a protein important in muscle function," says Disney. "It is this RNA-protein interaction that causes the disease."

The UB group has developed a method of precisely designing ligands with higher affinity and specificity for the RNA structure than natural protein.

"If it has a choice of which to bind, the RNA will bind to our rationally designed small molecule, potentially interrupting the interactions that lead to muscular dystrophy," says Disney.

The UB group's next step is to begin working to develop the small molecule into a viable pharmaceutical product by testing its efficacy in cell culture and a mouse model of the disease.

In addition to the promise the research holds for myotonic dystrophy, the development of the RNA-small molecule database marks the start of a new approach to developing cures for other RNA-mediated diseases.

"RNA structures in general are unexplored as drug targets in part because they are much more complex than DNA," says Disney. "We are using our database of RNA structures that bind small molecules to compare to all toxic RNAs. Once an RNA sequence is found that causes disease, we can input that sequence into our database and search for structures in the disease-causing RNA that bind one of our small molecules. If we find one, we then have identified a lead molecule for exploring as a potential pharmaceutical compound."

Disney also is developing computational tools to mine the human genome against the RNA database in order to identify new RNA targets to which this approach can be applied. In this work, he is collaborating with computational scientists at the Center for Computational Research (CCR) in UB's New York State Center of Excellence in Bioinformatics and Life Sciences.

He notes: "It would be hard to envision doing this work without the support of CCR."

Disney's research has been supported by a James D. Watson Young Investigator Award from the New York State Foundation for Science, Technology and Innovation, the UB 2020 Interdisciplinary Research Development Fund, the Research Corporation, the Camille and Henry Dreyfus Foundation, the National Institutes of Health, the Wellstone Foundation and UB's New York State Center of Excellence in Bioinformatics and Life Sciences.

He is an active member of the University at Buffalo's 2020 strategic strength in Molecular Recognition in Biological Systems and Bioinformatics.

Disney's co-authors on the papers are: Jonathan M. French and Melissa M. Lee, graduate students in the UB Department of Chemistry; Alexei Pushechnikov, Ph.D., formerly a postdoctoral researcher in the UB Department of Chemistry; Jessica L. Childs-Disney, Ph.D., of the Department of Chemistry and Biochemistry, Canisius College; Charles A. Thornton, M.D., of the Department of Neurology at the University of Rochester; and Krzysztof Sobczak, Ph.D., formerly a post-doctoral researcher at the University of Rochester.

The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.

(Posted Aug 07, 2009)

Saudi University Officials Visit UB to Discuss Possible Collaborative Research

Visit Prompted by Groundbreaking Paper on Science of Cancer

By Lois Baker

University at Buffalo officials spent two days last week meeting with representatives of King Saud University in Saudi Arabia to discuss potential research collaborations engendered by groundbreaking Saudi research conducted in collaboration with UB researchers.

The research, published in the August issue of Neoplasia, describes, in a mouse model, a novel vaccine immunotherapy approach that may be able to decrease the tumor burden in cancer patients by blocking cancer metastasis.

Adel Almogren, Ph.D., professor in the College of Medicine's Department of Pathology and Immunology at King Saud University, is one of the principal authors on the paper. Kate Rittenhouse-Olson, Ph.D., professor of biotechnical and clinical laboratory sciences in UB's School of Medicine and Biomedical Sciences, is senior author.

Almogren conducted research at UB as a master's student under Rittenhouse-Olson's direction, and has been in contact as a collaborator since leaving Buffalo.

The publication drew major interest from officials at the highest levels of Saudi government to increase UB collaborations with King Saud University, and raised the possibility of research funding from Saudi Arabian sources.

The Neoplasia paper generated a story in the July 21 issue of USA Today, which set in motion a series of events that resulted in the arrival at UB of Almogren and Mezyad Alterkawi, Ph.D., an emissary from King Saud University and CEO at the Riyadh Techno Valley Incubator in Saudi Arabia.

During their two-day visit, Almogren and Alterkawi awarded Rittenhouse-Olson the King Saud University gold medal for research excellence, and presented an invitation letter from the president of King Saud University to UB President John B. Simpson, which UB Provost Satish Tripathi, Ph.D., accepted in Simpson's absence.

The visitors met also with Michael Cain, M.D., dean of the UB medical school, John Wood, associate vice provost for International Education, and other UB leaders, to discuss their vision of collaborating further with Rittenhouse-Olson and UB. King Abdullah bin Abdul Aziz al-Saud is interested in increasing research and research collaborations in order to build a knowledge-based economy in Saudi Arabia, the Saudi representatives reported. A UB-Saudi Arabia research link also may benefit the emergence of Buffalo's knowledge-based economy, UB officials said.

Rittenhouse-Olson, along with Jamie Heimburg-Molinaro and Susan Morey, members of her research team, have been invited to King Saud University in the fall to meet with the university president and discuss further research collaborations.

King Saud University is the premier research institute in Saudi Arabia and is leading the nation's efforts to achieve transition to a knowledge-based economy in the kingdom.

Other collaborators in this work were Olga V. Glinskii and Vladislav V. Glinsky of the University of Missouri and Harry S. Truman Veterans' Hospital, Rene Roy of the University of Montreal, Richard P. Cheng of National Taiwan University, and Gregory Wilding of UB.

The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.

(Posted Aug 03, 2009)

Chromadex moves Koffas technology with SBIR

Abstract from knowledgeexpress.com at

http://www.knowledgeexpress.com/recordview.asp?rid=84948&dbid=2&ListLoc=0&SourceFilter=

This Small Business Innovation Research (SBIR) Phase I project "Microbial Production of Selected Anthocyanins", aims to establish cost-effective methodologies for the efficient production of anthocyanins from genetically engineered bacteria.

Anthocyanins are plant secondary metabolites that are mainly responsible for the colors in plant tissues, primarily reds, purples and blues. They are non-toxic and have been observed to possess antioxidant, anticancer and anti-inflammatory activities, thus making them attractive candidates in the pharmaceutical, dietary supplement,and food colorants industries. As the benefits of anthocyanins continue to gain definition, the demand for these compounds is growing exponentially. Unfortunately, the cost of attaining pure or well defined mixtures of anthocyanins using conventional techniques outweighs the potential market return. By using engineered microbes, large batches of selected anthocyanins can theoretically be produced, making compound isolation efficient and cost effective. The broader impacts of this research are to produce cost-effective natural and non-natural anthocyanins, whose health benefits can be investigated; allow students to participate and train in the ongoing development of a microbial production platform; foster a collaboration between a U.S. academic institution and a U.S. company, and contribute to the expansion of a small specialty chemical company.

This project will utilize students to create a biosynthetic system that will produce a vast array of anthocyanins. As these compounds are attained they will be moved to the market place, where they can be further researched by academia, industry and governmental agencies.

(Posted Jul 01, 2009)

UB to host major biomedical ontology conference

by PATRICIA DONOVAN

Whether and how medical personnel and their digital systems can talk to one another in a meaningful way is a subject pertinent to the health of patients about whom they “converse.”

Internationally recognized ontologist Barry Smith, SUNY Distinguished Professor and Julian Park Professor of Philosophy at UB, points out, however, that these electronic systems frequently do not employ the same ontology—or system of meaning—which results in harmful, and even fatal, consequences for patients.

This problem will be addressed by a vast array of philosophers, biomedical researchers and informatics scientists July 24-26 at what Smith calls “one of the most important meetings on this subject in years”: the International Conference on Biomedical Ontology, hosted by UB.

Smith, director of the National Center for Ontology Research (NCOR), was one of the first researchers who aimed to develop a sound medical ontology that would enable various knowledge-processing applications to communicate with one another. This requires the definition, organization, visualization and utilization of semantic spaces created from biomedical knowledge-processing applications.

Smith is co-chairing the conference with Suzanna Lewis, who heads the Berkeley Bioinformatics Open-source Projects group at Lawrence Berkeley National Laboratory.

http://icbo.buffalo.edu/ to access the conference program. For additional information, call 645-0160 or email ncor@buffalo.edu.

Smith says the conference will draw biologists, clinicians, informatics specialists and ontologists whose research involves innovative technology and methods that create, disseminate and manage biomedical information in a form that can be processed by machine.

“This subject is becoming a huge phenomenon,” he says, “because President Obama wants to invest a great deal in the development and use of electronic medical record systems. A shared ontology is one of the essential ingredients that would permit such programs to work across systems, geographic boundaries and institutions.”

In addition to the formal program, half-day pre-conference tutorials and two-day classes will be offered to participants July 20-23. See .

The conference is sponsored by the UB College of Arts and Sciences; NCOR, headquartered at UB and Stanford University; and the National Center for Biomedical Ontology, one of the National Centers for Biomedical Computing supported by the National Institutes of Health Roadmap for Medical Research, with generous support from the National Human Genome Research Institute.

In addition to Smith and Lewis, scientists involved in its planning are from Cambridge University, The Jackson Laboratory (Maine), the University of Chicago, Stanford, Science Commons, the European Bioinformatics Institute, the University of Pennsylvania, the NIH Library of Medicine, Duke University, the University of California-San Diego, Berkeley Labs, UB, the University of Washington, the University of Manchester (UK), Charité Hospital (Berlin), the University of Texas Southwest Medical Center, Georgetown University, the University of Delaware, the University of Michigan and the Royal Society of Chemistry.

(Posted Jul 01, 2009)

Grant gives lift to Kinex cancer research

Read Complete Story

(Posted May 27, 2009)

State grant aims to help UB build clean-energy businesses

Read Complete Story

(Posted May 15, 2009)

NYSERDA Awards $1.5 Million to UB to Establish Clean Energy Business Incubator Program

Ellen Goldbaum

The New York State Energy Research and Development Authority (NYSERDA) today announced an award of $1.5 million to the University at Buffalo Office of Science, Technology Transfer and Economic Outreach to establish a clean energy business incubator program that will provide business support to accelerate the successful development of early-stage, clean energy technology companies in Western New York.

Through this award and other ongoing efforts, NYSERDA is building the capacity to foster innovative clean energy companies, grow the clean energy industry in New York and expand the State's "green collar" workforce.

"One way New York is leading the nation in the clean energy revolution is through fostering successful partnerships between early-stage clean energy businesses and regional incubators that help them grow and compete in the global marketplace," said Francis J. Murray Jr., president and CEO of NYSERDA. "The funding we announce today represents Gov. David A. Paterson's commitment to invest in the infrastructure that will help innovators develop their products, take their ideas to the market and expand our state's clean energy industry."

UB's program, Directed Energy, is designed to utilize the technical expertise of scientists and engineers at the university with the business development skills of the university's Technology Incubator in order to foster clean energy companies and job growth in Western New York. NYSERDA funds are intended to assist companies throughout the incubation process, and to develop a financially self-sustaining program that makes Western New York a regional center for developing clean energy technologies.

"We are creating a regional foundation for a healthy green economy in Western New York," said Martin Casstevens, business formation and commercialization manager for the UB Office of Science, Technology and Economic Outreach (STOR) and director of Directed Energy. "This is just the beginning of a long-term program to concentrate resources and technical skills to grow alternative energy businesses in Western New York. We have programs to assist local energy companies, energy entrepreneurs and scientists to develop sustainable clean energy technologies."

The Directed Energy program also will work with the Buffalo-Niagara Enterprise to attract energy companies to Western New York by marketing the region's natural and institutional assets. In addition, Directed Energy will develop curricula to better prepare university students for the green economy and to help companies provide quality continuing education to employees. Alfred University, Buffalo's Insyte Consulting and Buffalo-Niagara Enterprise, UB's Center for Industrial Effectiveness (TCIE), Lockport's Harrison plant incubator, Niagara County's Vantage Center and Batavia's Harvester Center are partners in UB's Directed Energy program.

"Throughout the state, from garages and workshops to university laboratories, innovative New Yorkers are working to meet our energy requirements in ways that improve our environment and make our economy more robust," Murray added. "Under the leadership of Gov. Paterson, the prospect to start and grow renewable and clean energy technology companies right here in New York remains bright."

Paterson's Renewable Energy Task Force Report, issued in February 2008, made several recommendations calling for increased support to clean energy businesses. NYSERDA has led efforts to establish clean energy business incubators that provide guidance, technical assistance, and consultation to young growing companies, so they contribute to New York State's economy and are well positioned to compete on national and global levels.

Through the use of innovation and technology, NYSERDA is working to solve New York's difficult energy and environmental problems in ways that improve the state's economy. Effective business assistance programs will not only allow clean energy companies achieve growth and succeed globally, but also meet increased demand for clean energy and energy-efficient products. By diversifying our industrial and manufacturing resources with growing early-stage clean energy technology companies, New York can assure its continuing position as a leader in the innovation economy.

NYSERDA, the New York State Energy Research and Development Authority, offers programs, technical support and funding to help businesses, municipalities, research institutions and consumers become more energy-efficient, protect the environment and save money. By supporting the development and commercialization of new technologies, NYSERDA programs move New York toward a clean energy economy, deliver economic benefits and prepare New York workers for green-collar jobs. NYSERDA program staff brings significant expertise and evaluates energy-related projects to ensure the best outcome. NYSERDA invests in programs that support the state's energy goals -- reducing energy consumption while promoting the use of renewable resources and protecting the environment. NYSERDA, a public benefit corporation, has been helping New York save energy since 1975.

The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate, and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.

(Posted May 14, 2009)

UB Business Partners Day - June 4, 2009

To Register and see details of the event, go to:

http://www.buffalo.edu/business_partners_day/

Learn how profitable a partnership with UB can be. Discover the many ways the university advances economic growth and business development in its partnerships with industry throughout Buffalo Niagara. View exhibits and attend workshops where you’ll discover the groundbreaking research as well as the successful university collaborations with business, government, and community entities.

Celebrate the many and diverse university/industry partnerships that are revitalizing Upstate New York. Learn how your business can profit from a partnership with UB through the range of entrepreneurial efforts expanding our economy.

Business Partners Day allows attendees to plan the day according to interests—feel free to take in as much as you want. Experience the informative exhibits and workshops throughout the morning and the motivating luncheon program at noon.

Thursday, June 4, Adam’s Mark Hotel

STOR will participate in several Sessions:

Session 1 9:00-9:50 Looking for Early Stage R&D Federal Funding? Learn How It Works

Session 2 10:00-10:50 Hickey Cardiac Monitoring System – a Collaborative Path to Market

Session 3 11:00-11:50 Looking for Directed Energy to Grow Your Technical Company?

(Posted May 10, 2009)

UB announces Panasci winners

Copy and paste the link below in your browser to see this article

http://www.bizjournals.com/buffalo/stories/2009/04/27/daily30.html

(Posted Apr 29, 2009)

UB and RPCI Researchers named Inventors of the Year

The Niagara Frontier Intellectual Property Law Association held its 34th Annual Western New York Inventor of the Year Awards Banquet on Thursday, April 16, 2009, at the Buffalo Museum of Science, a fitting location to honor Niagara Frontier inventors. Awards recognized inventors of patents issued in 2008 in the categories of Life Sciences, Physical Sciences, Small Entity/Independent Inventor, as well as an overall Inventor of the Year Award.

University at Buffalo and Roswell Park Cancer Institute researcher collaborators were named Inventor of the Year and 1st Place winners in the Life Science category for their patent covering the use of ceramic-based nanoparticles to deliver photodynamic therapy compounds.

Congressman Chris Lee presented the Keynote Address. He emphasized the importance of intellectual property and manufacturing to the health of the U.S. economy, pointing to his own experiences at Enidine Inc. growing a business based on intellectual property and manufacturing. He congratulated all of the nominees for their innovative work. Lee also reported on a bill he is co-sponsoring to make the R&D tax credits permanent and to provide tax incentives for manufacturing in the U.S.

University at Buffalo inventors were recognized with the following awards:

Inventor of the Year 1st Place, Life Sciences

U.S. Patent 7,364,754 Ceramic Based Nanoparticles for Entrapping Therapeutic Agents for Photodynamic Therapy and Method of Using Same

Inventors: UB inventors Paras Prasad, Indrajit Roy, Earl J. Bergey, Tymish Y. Ohulchanskyy, Haridas Pudavar, and co-inventors from RPCI, Allan R. Oseroff, Ravindra K. Pandey and Janet Morgan

Ceramic-based nanoparticles are used to encapsulate drugs used for photodynamic therapy (PDT) and selectively deliver them to target sites (e.g. cancer sites). PDT involves the excitation of chemical photosensitizers with light. Excess energy from the photoexcited drugs transfers to surrounding molecular oxygen, resulting in the formation of reactive oxygen species which act to kill, for example, targeted cancer cells. PDT drugs are poorly water soluble, therefore, encapsulating them in nanoparticles results in stable water dispersion necessary for biomedical applications. The patent is licensed to Nanobiotix Inc. and Malasian Biotechnology Corporation.

Other UB Inventors recognized:

3rd Place, Life Sciences

U.S. Patent 7,374,755 Therapeutic Use of Anti-TF-Antigen Antibody

Inventor: Kate Rittenhouse-Olson

The patent covers an antibody with the potential to inhibit breast cancer metastasis. "The monoclonal antibody we developed has been shown to extend significantly the survival of mice with human breast-cancer tumors and to inhibit the cancer's spread to the lungs in the animals by more than 50 percent," said inventor Kate Rittenhouse-Olson, Ph.D., associate professor of clinical and laboratory sciences in the UB School of Medicine and Biomedical Sciences.

1st Place, Physical Sciences

U.S. Patent 7,425,826 Selectively Conductive Structure Wherein a Magnetic Conductor Is Sized to Have a Cross-Section Diameter Similar to a Fermi Wavelength Of Electrons

Inventors: Harsh Deep Chopra, Zonglu (Susan) Hua, Jason N. Armstrong, Matthew R. Sullivan

The patent describes the working principles of how data can be stored in atomic sized devices. It would enable multiple bits to be stored in devices the size of a single atom. In the age of IT, there is an increasing need and trend to increase data storage capacity in devices that are being made progressively smaller. The ultimate size limit is the atom. This work on Ballistic Magnetoresistance (BMR) would enable storage of unprecedented amounts of data in atomic sized memory devices. Giant Magnetoresistance (GMR) was the last major advance in data storage and in turn enabled increasingly dense hard drives. Now, hard drive bit density advances are pushing the limits of GMR capabilities. As the size of stored bits gets smaller, resulting in weaker magnetic fields, more sensitive technology, such as this BMR device described in this invention, will be required to read the bits.

2nd Place, Physical Sciences

U.S. Patent 7,335,333 Method of Altering a Fluid-Borne Contaminant

Inventors: James F. Garvey, John A. Lordi, Joseph C. Mollendorf, James D. Felske

The patented device rapidly elevates the pressure and temperature of the air circulated by the pump and destroys contaminents. The BioBlower can rapidly and continuously eradicate airborne biological pathogens, such as anthrax, and it has the potential to eradicate other airborne pathogens, such as avian flu, SARS and influenza viruses. It is licensed to Buffalo BioBlower Inc. Drs. Garvey and Lordi are company founders.

The Niagara Frontier Intellectual Property Law Association (NFIPLA) is an organization of intellectual property (IP) professionals dedicated to the creation, protection, and development of IP in Western New York.

(Posted Apr 17, 2009)

Safely sedating ICU patients for less

By ELLEN GOLDBAUM

A new, recently licensed medical device developed by UB researchers would introduce into intensive-care settings the powerful and effective method of anesthetizing patients that works so well in the operating room.

The new UB ventilator has the potential to shorten the time a patient stays in the intensive care unit (ICU) because it will greatly reduce complications and habituation to sedatives used in the ICU. It also is expected to be more cost-effective than current methods of ventilating ICU patients. The device also may have promising applications in treating large numbers of patients during pandemics or other events with mass casualties because it can safely enable multiple patients to share a single ventilator without the risk of cross-contamination.

The device is designed to cost-effectively deliver to patients small amounts of powerful inhalation anesthetic agents as they breathe or are mechanically ventilated. The portable patient ventilator was invented by Bradley Fuhrman, professor of pediatrics and anesthesiology, and chief of critical care at Women & Children’s Hospital of Buffalo, and Mark Dowhy, director of the Pediatric Critical Care Laboratory in the UB Department of Pediatrics; both are on staff in the UB School of Medicine and Biomedical Sciences.

The invention, which has been presented at numerous technology exhibitions, including the 2008 World’s Best Technologies Showcase, was licensed from UB to Medical Conservation Devices (MCD) of Buffalo, located in UB’s New York State Center of Excellence in Bioinformatics and Life Sciences.

Fuhrman and Dowhy, who are founding partners in MCD, received the UB Entrepreneurial Spirit Award at the recent UB Inventors and Entrepreneurs Reception.

MCD is raising funds to further develop the prototype for FDA medical-device evaluation. Initial prototype devices have been validated in laboratory experiments. First Wave Technologies Inc. is a partial owner and manager of MCD. It is a technology-development company that partners with UB’s Office of Science, Technology and Economic Outreach to expand the commercialization of early-stage university technologies utilizing private-sector resources.

A key advantage of inhaled anesthetics over intravenous sedation, which is the current approach in the ICU, is that inhaled anesthesia delivers and clears sedatives by way of the lungs, bypassing the metabolic and excretory systems. That’s a critical factor, Fuhrman said, for patients who have sustained damage to their kidneys or livers as a result of their illness.

When anesthesia is delivered through the lung, there is a much more rapid onset of effect and much quicker reversal once it is removed, an important consideration especially in patients who need to be frequently or abruptly awakened, such as children who have suffered trauma to the skull.

The invention addresses a problem common in ICU settings in which sedation must be deep enough that the patient is not aware of pain, but not so deep that it will cause withdrawal issues once the patient is no longer sedated.

“We administer significant amounts of narcotics and other agents to keep patients comfortable,” explained Fuhrman. “But if we sedate them too well, we often face problems with withdrawal.”

In those cases, patients can exhibit shakiness, combativeness and anxiety, symptoms that are treated with methadone, usually requiring the patient to remain in the ICU for several more days.

By contrast, he noted, patients in operating rooms are sedated using intravenous sedatives combined with precisely controlled concentrations of inhalation agents delivered by an expensive, specially designed anesthesia ventilator. An anesthesiologist or nurse anesthetist then monitors and controls a patient’s vital signs and depth of anesthesia on a moment-by-moment basis.

“It’s that kind of control that we are seeking to duplicate at each ICU bedside,” said Fuhrman.

“With our ventilator, the patient is continually rebreathing the same anesthetic and oxygen mixture, so the amount of anesthetic that is used can be reduced by about 80 percent,” he said.

The ventilator was developed with initial assistance from the UB Product Development Fund and the UB Center for Biomedical and Bioengineering Technology.

(Posted Apr 08, 2009)

Patented inventions double

By ELLEN GOLDBAUM

An antibody with the potential to stop breast cancer in its path. A nanoparticle that can address a side effect of the treatment that hemophiliacs cannot live without. A “quantum dot” with the potential to treat cancer or harvest the power of the sun. An air purifier that kills the world’s nastiest toxins.

No, they’re not the stuff of science fiction.

These are some of the new inventions that were patented in 2008 by UB researchers, a year that has seen the number of UB patents more than double from nine in 2007 to 21 last year.

More than 40 of these UB researchers were honored last week at the UB Inventors and Entrepreneurs Reception for their efforts to bring their research out of the lab and into the marketplace.

The reception also honored 11 UB technologies that were licensed to industry and the three most recent “graduates” of UB’s Technology Incubator.

“The jump we saw this year in our patent activity is a testament to the intense and growing commitment we are seeing among our scientist-entrepreneurs, who increasingly seek ways to get their scientific advances out into society,” said Robert J. Genco, vice provost and director of the Office of Science, Technology Transfer and Economic Outreach (STOR), which co-sponsored the event with the Office of the Vice President for Research.

“They know that the most important scientific discovery in the world may provide little value to society if it goes no further than a journal publication,” he continued. “Today, UB is honoring its professors who have taken the critical steps toward using their scientific and technological expertise to address some of the world’s most profound problems.”

Genco and Kenneth M. Tramposch, associate vice president for research, addressed the inventors. President John B.Simpson and Provost Satish K. Tripathi also congratulated the inventors.

Some of the newly patented inventions are:

• An antibody with the potential to stop breast cancer metastasis. “The monoclonal antibody we developed has been shown to extend significantly the survival of mice with human breast-cancer tumors and to inhibit the cancer's spread to the lungs in the animals by more than 50 percent,” said lead investigator Kate Rittenhouse-Olson, associate professor of clinical and laboratory sciences, School of Medicine and Biomedical Sciences.

• A nanoparticle that treats hemophiliac patients who develop resistance to Factor VIII. “Our multifunctional, lipid nanoparticle improves the safety and efficacy of the protein by multiple mechanisms, improving stability of the protein, altering the immune response and making the particle stay in the blood longer,” said lead investigator Sathy Balu-Iyer, associate professor of pharmaceutical sciences, School of Pharmacy and Pharmaceutical Sciences.

• A quantum dot with the potential to treat cancer or harness solar energy. “Our process for synthesizing these silicon nanoparticles makes them potentially useful for various applications, including biological imaging and diagnostics, solar cells and light-emitting diodes,” said Mark T. Swihart, associate professor of chemical and biological engineering, School of Engineering and Applied Sciences and lead investigator.

• An air sterilizer that kills every biological agent it meets. “The BioBlower can rapidly and continuously kill airborne biological pathogens, such as anthrax, and it has demonstrated the ability to eradicate other airborne pathogens, such as avian flu, SARS and influenza viruses,” said James F. Garvey, professor of chemistry, College of Arts and Sciences, and lead investigator.

Also presented at the reception was the 2008 UB Entrepreneurial Spirit Award recognizing researchers who founded a company to license a UB technology. This year, it was presented to Bradley P. Fuhrman, professor of pediatrics and anesthesiology, School of Medicine and Biomedical Sciences, and chief of critical care, Women & Children's Hospital of Buffalo, and Mark Dowhy, director of the Pediatric Critical Care Laboratory, UB Department of Pediatrics.

The invention was licensed from UB to Medical Conservation Devices (MCD) of Buffalo, located in UB's New York State Center of Excellence in Bioinformatics and Life Sciences. Fuhrman and Dowhy are founding partners in MCD, which is raising funds to further develop the prototype for FDA medical-device evaluation.

The event also will honor the three “graduates” of the UB Technology Incubator, which now have expanded into their own space. They are:

• Absolute Energy, moving to Grand Island, a complete Energy Management Services and IT sourcing partner.

• Lynx Technologies, moving to Grand Island, provides companies managing large networking computing environments with high-availability, high-reliability systems.

• Integral Information Systems, moving to Buffalo, a developer of advanced analytical software and decision support systems for health care providers.

(Posted Mar 06, 2009)

UB inventors named on patents

The following UB inventors were named on patents in 2008:

• John Lordi, James Felske and Joseph Mollendorf, Mechanical and Aerospace Engineering, and James Garvey, Chemistry, patent 7,335,333 Method of Altering a Fluid-Borne Contaminant.

• Mattheos Koffas, Chemical and Biological Engineering, and collaborators Effendi Leonard, Yajun Yan and Joseph Chemler, formerly of Chemical and Biological Engineering, patent 7,338,791 Production of Flavonoids by Recombinant Microorganisms.

• Sathy Balu-Iyer and Robert Straubinger, Pharmaceutical Sciences, and collaborators Karthik Ramani and Vivek Purohit, formerly of Pharmaceutical Sciences, patent 7,351,688 Compositions and Methods for Less Immunogenic Protein Formulations.

• Bradley P. Fuhrman and Mark S. Dowhy, Pediatrics, patent 7,367,335 Therapeutic Agent Delivery Device and Method.

• Mark Swihart, Chemical and Biological Engineering, and collaborators Yuanqing He and Xuegeng Li, formerly of Chemical and Biological Engineering, patent 7,371,666 Process for Preparing Luminescent Silicon Particles.

• Kate Rittenhouse-Olson, Biotechnical and Clinical Laboratory Sciences, patent 7,374,755 Therapeutic Use of Anti-TF-Antigen Antibody.

• Chunming Qiao, Computer Science and Engineering, and collaborators Yizhi Xiong and Dahai Xu, formerly of Computer Science and Engineering, patent 7,398,321 Segment Protection Scheme for a Network.

• Kenneth Hoffmann, Neurosurgery, and collaborator Satoru Ohishi, a non-UB inventor, patent 7,412,023 X-Ray Diagnostic Apparatus.

• Wesley L. Hicks Jr., Otolaryngology; Frank V. Bright and Joseph Gardella, Chemistry; Alexander N. Cartwright, Electrical Engineering; Robert Hard, Pathology and Anatomical Sciences; Bahattin Koc, Industrial and Systems Engineering; and Jamson S. Lwebuga-Mukasa, Medicine, and collaborator Rena Bizios, a non-UB inventor, patent 7,417,174 Resorbable Laminated Repair Film and Method of Using Same.

• Harsh Deep Chopra and Zonglu Hua, Mechanical and Aerospace Engineering, and collaborators Matthew R. Sullivan and Jason N. Armstrong, Mechanical and Aerospace Engineering, patent 7,425,826 Selectively Conductive Structure Wherein a Magnetic Conductor is Sized to Have a Cross-section Diameter Similar to a Fermi Wavelength of Electrons.

• Timothy F. Murphy and Sanjay Sethi, Medicine, and collaborator Thomas Hiltke, formerly of Medicine, patent 7,429,388 Vaccine for Non-Typeable Haemophilus Influenzae Infection.

• Terry D. Connell and Michael W. Russell, Microbiology and Immunology, and collaborators Sergio Arce and Hesham Nawar, Microbiology and Immunology, patent 7,455,843 Adjuvant Activities of Mutants of LT-IIa and LT-IIb Enterotoxin Lacking Binding to Ganglioside.

• Anthony Campagnari and Nicole Luke, Microbiology and Immunology, and collaborators Amy Howlett and Katie Edwards, Microbiology and Immunology, and Kristin Furano formerly of Microbiology and Immunology, patent 7,468,256 Tools for Detecting Moraxella Catarrhalis.

• Paras N. Prasad, Chemistry, and collaborators Guang S. He, Chemistry, and Qingdong Zheng formerly of Chemistry, patent 7,449,578 Two-Photon Absorbing Materials with Quenched Emission.

• Paras N. Prasad and Aliaksandr Kachynski, Chemistry, and collaborators Andrey Kuzmin, Chemistry; and Haridas Pudavar, formerly of Chemistry, patent 7,413,341 Imaging Methods.

• Paras Prasad, Indrajit Roy, Earl J. Bergey, Tymish Y. Ohulchanskyy, Chemistry, and collaborators Haridas Pudavar, formerly of Chemistry, and Janet Morgan and Allan Oseroff, of Roswell Park Cancer Institute, patent 7,364,754 Ceramic Based Nanoparticles for Entrapping Therapeutic Agents for Photodynamic Therapy and Method of Using Same.

• Thomas A. Szyperski, Chemistry, and collaborators Hanudatta S. Atreya and Seho Kim, formerly of Chemistry, patent 7,365,539 Method of Using G-Matrix Fourier Transformation Nuclear Magnetic Resonance (GFT NMR) Spectroscopy for Rapid Chemical Shift Assignment and Secondary Structure Determination of Proteins.

• Thomas A. Szyperski, Chemistry, and collaborator: Seho Kim formerly of Chemistry, patent 7,396,685 Phase-Sensitively Detected Reduced Dimensionality Nuclear Magnetic Resonance Spectroscopy for Rapid Chemical Shift Assignment and Secondary Structure Determination of Proteins.

• Thomas A. Szyperski, Chemistry, and collaborator David Parish, Chemistry, patent 7,408,346 Simultaneous Phase Cycling for Nuclear Magnetic Resonance Spectroscopy.

• Huw M. L. Davies and Ravisekhara P. Reddy, formerly of Chemistry, patent 7,385,064 Catalysts for Use in Enantioselective Synthesis.

• Huw M. L. Davies and Timothy Gregg, formerly of Chemistry, patent 7,443,376 Tropane Prodrugs with Central Nervous System Activity.

The following “Visionary Innovators” invented technologies that were licensed to an industrial partner in 2008:

• Anthony A. Campagnari, Microbiology and Immunology, Steven Gill, Oral Biology, and Thomas Russo, Medicine, developed Microorganisms as Controls for Assay Specificity and Detection, which was licensed to ZeptoMetrix Corp.

• Ali El-Solh, Medicine, developed CPAP Titration Using Artificial Neural Network, which was licensed to Universal Diagnostics Testing LLC.

• Timothy F. Murphy, Medicine, developed Haemophilus influenzae Strain 11P6H, which was licensed to a large pharmaceutical firm.

• David Pendergast, Physiology and Biophysics, and collaborators Albert C. Termin II formerly of Athletics, and John C. Zaharkin and Michael Zaharkin formerly of Physiology and Biophysics, developed System and Method for Training a Swimmer, which was licensed to Astrum SSL Solutions Inc.

• Ingvald M. Tyssebotn and Clas E. Lundgren, Physiology and Biophysics, and collaborators Hugh VanLiew and Mark Burkard, formerly of Physiology and Biophysics, developed Method of Enhancing Transport of Gases, which was licensed to NuvOx Pharma LLC.

• Venugopal Govindaraju, Computer Science and Engineering, and collaborators Ramanaprasad Vemulapati, Srirangaraj Setlur and Zhixin Shi, CEDAR, developed FieldXtract—A Software Toolkit for Extraction and Automated Reading of Machine Printed and Handwritten Form Fields, which was licensed to KYOS Systems Inc.

• Bradley P. Fuhrman and Mark S. Dowhy, Pediatrics, developed Universal Isolator, which was licensed to Medical Conservation Devices LLC.

• Mattheos Koffas, Chemical and Biological Engineering, and collaborators Joseph Chemler, Chemical and Biological Engineering; Effendi Leonard and Yajun Yan, formerly of Chemical and Biological Engineering; and Ralph Bernacki, Roswell Park Cancer Institute, developed Production of Flavonoids by Recombinant Microorganisms, which was licensed to ChromaDex Inc.

• Aiming Yu, Pharmaceutical Sciences, developed CYP2D6 and CYP3A4 Double Transgenic Mice, which was licensed to a large pharmaceutical firm.

• Thomas A. Szyperski, Chemistry, and collaborators Alexandre Eletski, Chemistry; Seho Kim and Hanudatta S. Atreya, formerly of Chemistry, developed Reduced Dimensionality and G-Matrix Fourier Transformation Techniques for NMR, which was licensed to a large pharmaceutical firm.

• Laurie K. Read, Microbiology and Immunology, and collaborator John C. Fisk, Microbiology and Immunology, developed Type III Trypanosoma brucei Arginine Methyltransferase, which was licensed to CH3 BioSystems LLC.

(Posted Mar 06, 2009)

Researchers Apply Systems Biology and Glycomics to Study Human Inflammatory Diseases

Ellen Goldbaum

goldbaum@buffalo.edu

BUFFALO, N.Y. -- An innovative systems biology approach to understanding the carbohydrate structures in cells is leading to new ways to understand how inflammatory illnesses and cardiovascular disease develop in humans. The work was described in two recent publications by University at Buffalo chemical engineers.

Supported by research grants from the National Institutes of Health, the ultimate goal of the project is to define novel strategies to perturb the glycome -- the complete set of an organism's carbohydrate structures in cells -- in ways that lead to the identification of new targets and molecular therapies to combat a broad range of inflammatory diseases.

The binding of white blood cells to blood vessels is a key step in the progression of inflammatory diseases, explained Sriram Neelamegham, Ph.D., UB professor of chemical and biological engineering in the School of Engineering and Applied Sciences, and co-author of both papers. He also is an investigator with UB's New York State Center of Excellence in Bioinformatics and Life Sciences.

"Our goal is to find ways to alter carbohydrate structures or glycans on the surfaces of white blood cells," he said.

But in order to do that, researchers need a far more detailed picture of these structures and the highly complex interactions between glycans, enzymes, genes and proteins, all of which can influence the development of inflammatory disease.

To do this research, Neelamegham's lab uses systems biology, a mathematical and experimental approach that focuses on whole systems of complex biological functions and interactions instead of studying individual units, such as a single gene or protein, in isolation.

"Systems biology is well-suited to this research because it helps us develop the mathematical concepts to enable us to influence and enhance our understanding of how the glycome functions," said Neelamegham. "This then produces clues on how we might manipulate the adhesivity of white blood cells to the blood vessel wall."

Glycans are carbohydrate molecules that mediate the microscopic interactions between white blood cells and blood vessel walls. These interactions play a major role in painful and debilitating inflammatory medical conditions such as asthma, psoriasis, Crohn's disease, reperfusion injury and other cardiovascular ailments.

In a recent paper in The FASEB Journal, the UB researchers describe one of the first studies to take a systems approach to the study of cellular glycosylation, the modification process that is responsible for the attachment of sugar structures to protein and lipid scaffolds. Such biochemical modifications are critical to diverse biological processes, including cell/organ development, immunity and cell adhesion. Abnormal glycosylation also is implicated in diverse diseases, including certain cardiovascular diseases and a cluster of congenital diseases termed Congenital Disorders of Glycosylation.

The paper demonstrates experimental techniques that measure enzyme reaction rates involved in glycosylation, and then draw critical correlations with gene expression, enzyme kinetics and the structures of glycans.

"These techniques enable us to move from genes to proteins and finally to the structures of glycans on cells and individual proteins," said Neelamegham.

The UB paper in Bioinformatics describes a computer model that uses the data produced by those experiments to establish a basis for predicting the structures of glycans on cell surfaces.

"The data produced experimentally allows us to determine key steps in the glycome reaction network that controls the final glycan structure that appears on cells," Neelamegham explained. "This approach then provides an in silico tool that can be applied to perturb the system of interest, such as the glycosylation network."

Those studies, in turn, he continued, can then generate new hypotheses that can be tested experimentally.

"Such an interative approach, using computational and experimental tools, can provide clues as to what reactions must be perturbed in order to alter the carbohydrate structure on cell surfaces in a defined manner," he explained.

The UB researchers noted that their computational and experimental approaches to the problem provide them with a unique insight.

"It's an extremely valuable way to apply engineering principles to biology, it's critical to merge both approaches," said Neelamegham.

In addition to providing new insights for the ultimate development of new drugs and therapeutic strategies, the UB research also is relevant to sectors of the biotech industry, which aim to apply glycan engineering principles during product development.

Coauthors on The FASEB Journal paper, are Dhananjay D. Marathe, research assistant in the UB Department of Chemical Engineering, as well as E.V. Chandrasekaran, scientist, Joseph T.Y. Lau, Ph.D., faculty member, and Khushi L. Matta, Ph.D., faculty member, at Roswell Park Cancer Institute.

Gang Liu, a UB graduate student in the UB Department of Chemical and Biological Engineering, and Marathe and Matta are co-authors on the Bioinformatics paper.

(Posted Oct 28, 2008)