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Source: Buffalo News
WASHINGTON — Upstate New York is not Silicon Valley, but many people would like it to be. Inventors and researchers from across the state, therefore, crammed into a Capitol Hill meeting room Wednesday to show their wares and hope for a little of the magic that techy types call "synergy."
"This is networking for us," said Dr. Bradley P. Furhman, professor of pediatrics and anesthesiology at the University at Buffalo and chief of critical care at Women & Children's Hospital. "This is a chance to meet people who may have an idea of how to facilitate our project, how to use the power of our university, the power of the government to help bring it to market."
With his colleague Mark S. Dowhy, Furhman has invented a portable ventilator that can be used by more than one patient at once.
It would be useful during pandemics, Furhman noted — although it won't be on the market in time for the the swine flu outbreak.
Sen. Kirsten E. Gillibrand, a Democrat, sponsored Wednesday's event to bring together inventors such as Furhman and congressional aides to spark activity in the state's high-tech sector.
"I'm hoping it creates jobs," Gillibrand said. "When you highlight companies like this, and you bring staffs from all over the Congress, they can see what new innovations are being made, what new products are being created. And then when it's time to apply for appropriations, to apply for grants, they'll be more receptive to these kinds of applications."
Indeed, money was on the minds of many of the innovators at the event.
Furhman noted that his enterprise, Medical Conservation Devices of Buffalo, had received a $900,000 grant from the National Institutes of Health for product development. But once it gets approval from the Food and Drug Administration, he will have to find money to bring it to market.
"We have a venture capital problem," he conceded. "We would really like to develop this as a Western New York company," but finding the funding to get the project off the ground has been difficult, he added.
Others saw the event more as a chance to mix, mingle and see what happens.
"Just interacting with all the other folks from New York State who have displays here has been very useful, to find out the exciting things going on and how maybe we can network or work with them," said Esther Sans Takeuchi, a UB engineering professor who recently won a National Medal of Technology and Innovation for her invention of the batteries used in many medical devices.
Thomas M. Pleban, executive vice president of Calspan, and Donald J. Goralski, senior program officer at UB's Multidisciplinary Center for Earthquake Engineering Research, pushed a Calspan-UB joint venture. The entities are building two test-bridges side-by-side on Calspan property in Ashford, just to see how they stand up over time to extreme conditions.
"The idea is to test and use the Buffalo climate to our advantage," Goralski said.
The UB Center, now dubbed MCEER, is also exploring how its earthquake research can be used in dealing with other types of disasters, he added.
As Goralski spoke, dozens of congressional staffers milled about the Kennedy Caucus Room in the Senate Russell Building, checking out displays from Cornell University, Harris Corp., the Brookhaven National Laboratory and scores of other centers of innovation.
TechNet, a bipartisan network of high-tech and finance executives from across the state, co-sponsored the event. And Rep. Chris Lee, R-Clarence, noted that boosting the state's high-tech companies was a bipartisan effort in Washington.
"[Research and Development] and investment in technology are what's going to make the difference in the United States," Lee said. "That's where government should be focusing. It's a cliche, but it's true."
posted by Brian Bell @ 9:31 AM
June 29, 2009
A research team at the University of Rochester Medical Center has received a Small Business Innovation Research (SBIR) grant to develop a new way to deliver proteins into human tissues, with a first application seeking to lower “bad” cholesterol.
Atherosclerosis develops when too much cholesterol injures blood vessel walls, and the body’s reaction to that injury clogs the vessels. The World Health Organization predicts that 20 million people per year will die from atherosclerosis, the leading causes of heart attack and stroke, by 2015. While many millions of people take drugs called statins to lower cholesterol levels, about one in five cannot, often because of too severe side effects, and need an alternative.
For two decades, researchers at the University of Rochester Medical Center have worked to determine how a family of proteins called “editing enzymes” make changes to genetic material that help cells defend against infection. Work in recent years has suggested that manipulating these enzymes may represent a new way to treat several diseases. The work funded by the new grant concerns the discovery that editing enzymes in liver cells also control the make-up of apolipoprotein B (apoB), a protein that carries cholesterol through the bloodstream, and that might be manipulated to lower cholesterol levels.
“This work is in the early stages, but we are tremendously excited about the potential of a new form of gene therapy to treat high cholesterol,” said Harold Smith, Ph.D., professor of Biochemistry and Biophysics at the University of Rochester Medical Center. Smith is co-PI on the SBIR grant with FirstWave Technologies, a commercialization company located in Buffalo. “Being able to deliver proteins therapeutically, say for enzyme replacement therapy, is a highly sought-after technology, and we are very encouraged in our initial success with a method that overcomes several past roadblocks.”
While genes are encoded in chains of deoxyribonucleic acids (DNA), they are copied into chains of messenger ribonucleic acids (mRNA) that are “read” by cellular enzymes that build proteins. Hereditary information is passed on this way naturally, and the designers of gene therapies have harnessed the process to counter disease.
In the current project, the team is using gene therapy to deliver the gene for an editing enzyme called APOBEC-1 into liver cells. Once in place, the gene codes for the building of the APOBEC-1 editing enzyme. Once built, APOBEC-1 begins to “edit” apoB mRNAs in liver cells, introducing a “stop signal” that orders the protein-building process to stop reading instructions early. This results in the building of a shortened form of apoB, apoB48, which is 48 percent of the length of standard apoB (apoB100).
The value of creating shortened apoB (apo48) can be explained in terms of the differences between proteins that carry cholesterol through the blood (lipoproteins). Dietary cholesterol is digested and carried to the liver, but cannot travel through the bloodstream to tissues that need it because it will not dissolve in blood. Because of its make-up, apoB can wrap up cholesterol, serving as the “truck” that delivers it to cells. The same process contributes to diseased arteries when cholesterol levels grow too high. ApoB is the protein part of both very low density lipoproteins (VLDL) and of low density lipoproteins (LDL), which are denser than VLDL, better able to penetrate blood vessel walls and more likely to cause atherosclerosis. The difference is crucial because VLDL particles containing apoB48 are quickly cleared from blood, while VLDLs with apoB100 linger. Lingering VLDLs are more likely to be turned into disease-causing LDL.
The challenge has been how to safely deliver APOBEC-1 as a treatment. To deliver a gene into cells, the designers of gene therapies need a delivery vehicle, or vector. Viruses have evolved to invade human cells and insert DNA into their prey, which makes them useful vectors once their harmful aspects are removed. A popular vector in gene therapy research is the adeno-associated virus (AAV), which harmlessly infects human cells. Once AAV has deposited a desired gene into a target cell, that gene directs the cell to build the therapeutic proteins, in this case APOBEC-1.
Past studies in the Smith Lab and elsewhere have shown that gene therapy can effectively deliver APOBEC-1 into liver cells and increase the editing of apoB mRNA to create more of the shortened version, apoB48. While this approach has been proven effective in reducing LDL levels in mice, it could still conceivably edit “off-target” mRNA chains to create abnormal proteins that signal for too much growth (cancer). Obviously, the risk of such over-editing must be eliminated before such therapies can come to fruition.
In an attempt to achieve this, Smith’s team attached two new units to the gene for APOBEC-1 as part of their gene therapy. The first is the gene for a protein called albumin that forces newly built APOBEC-1 to be quickly secreted from the liver cell producing it. Thanks to the albumin, the cell producing APOBEC-1 does not make too much of it and avoids related side effects. The second gene addition encodes TAT, a protein that enables the APOBEC-1, once secreted from the cell that produced it, to slowly soak into neighboring liver cells. While TAT delivery of proteins into neighboring cells is efficient, the enzymes, once soaked up, undergo a slow, refolding process that counters any sudden rise in editing activity, further improving safety.
The U.S. Small Business Administration (SBA) Office of Technology administers the SBIR Program that awards $2 billion to small, high-tech businesses each year. Smith’s lab at the Medical Center will conduct the experiments detailed in the project with the help of a $175,823 grant, which will fund a proof-of-concept study in animals to confirm that the new gene therapy delivery system works. If successful, it will be followed by larger animal studies and studies that experiment with different viral vectors for greatest efficacy and safety. FirstWave Technologies will partner with the Medical Center team to commercialize the technology as a next generation concept (filed as a provisional patent by the University of Rochester). The next step, animal testing of the delivery system, will be conducted in partnership with Scottsville-based STS, a toxicology testing facility.
“We seek to trigger some liver cells to edit their ApoB mRNA, but not others, and to find the right mix to lower LDL cholesterol just enough,” Smith said. “The virtue of our approach is that low viral doses can be used in gene therapy to create a mix of protein expression in the liver, which reduces the overall risk of therapeutic enzyme over-expression.”
posted by Brian Bell @ 3:11 PM
Original article can be found here:
![[ photograph ]](http://www.buffalo.edu/news/hires/BradleyFuhrman.jpg)
A new, cost-effective ventilator invented by Bradley Fuhrman (shown) and Mark Dowhy promises to shorten patient stays in the intensive care unit (ICU) because it greatly reduces complications and habituation.
Release Date: February 25, 2009
BUFFALO, N.Y. -- A new, recently licensed medical device developed by University at Buffalo 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 length of 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, Ph.D., 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 are founding partners in MCD, and will receive the UB Entrepreneurial Spirit Award at the UB Inventors and Entrepreneurs Reception on March 5.
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 then treated with methadone, usually requiring the patient to remain in the ICU for several more days.
By contrast, Fuhrman explained, 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 (CAT).
The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. 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 by Brian Bell @ 12:22 PM
Release Date
09/18/07
BUFFALO, N.Y. -- Microorganisms may soon be efficiently and inexpensively producing novel pharmaceutical compounds, such as flavonoids, that fight aging, cancer or obesity, as well as high-value chemicals, as the result of research being conducted by University at Buffalo researchers.In work that could transform radically the ways in which many of these compounds are produced commercially, the UB researchers are genetically engineering microorganisms, such as E. coli, into tiny, cellular factories.
Several patents related to this work have been filed by UB. The team also is in discussions with companies in the U.S. and abroad.
First Wave Technologies, Inc., a technology development company based in UB's New York State Center of Excellence in Bioinformatics and Life Sciences, which is collaborating with the UB group, recently received a highly competitive Phase I Small Business Innovation Research (SBIR) grant from the National Science Foundation to focus on the biosynthesis of a popular group of flavonoids called isoflavonoids.
"Ultimately, we want to be able to take a designed E. coli off of the shelf and drop into it the enzymes that constitute a particular biosynthetic pathway in order to make exactly the product we want," said Mattheos A. G. Koffas, Ph.D., assistant professor of chemical and biological engineering in the School of Engineering and Applied Sciences and leader of the UB team.
The UB approach to synthetic chemistry addresses some of the major challenges in conventional industrial production of specialty chemicals.
Through the use of specially adapted bacteria, specialized enzymes and natural feedstocks, microbial biosynthesis reduces or eliminates the need for petrochemical sources, elevated temperatures, toxic heavy metal catalysts, extremes of acidity and dangerous solvents, Koffas said.
In addition, the natural enzymes the UB researchers are using can facilitate chemical reactions that are difficult to accomplish through conventional chemistry, such as chiral synthesis, glycosylations and targeted hydroxylations, common but challenging steps in many syntheses.
"We are finding out how we can actually 'train' microbial systems to produce high yields of chemicals to be used as pharmaceuticals and to make production processes more efficient, less expensive and more environmentally friendly," Koffas said.
As with any commercial endeavor, process efficiency is a critical concern, he noted.
In work published in Applied and Environmental Microbiology in June, Koffas and his colleagues produced about 400 milligrams of flavonoids per liter of cell culture, far above the next highest yield of about 20 milligrams per liter produced by other microbial synthesis efforts.
"We have done this by increasing the amount of precursor available and re-engineering the native microbial metabolism," he explained, adding that they have taken different approaches to identifying the pathways that lead to the biosynthesis of precursors for desired compounds.
"Further improvement of production yields are possible and various approaches are being pursued by our team at this time," he said.
Another major challenge for microbial biosynthesis is that the enzymes required for certain chemical steps have special requirements that the host cell cannot meet efficiently, Koffas said. In some cases, the enzyme needs to be re-engineered, while in others the host cell needs modification.
Koffas' lab recently achieved the functional expression in E. coli of P450 monooxygenases, enzymes that are used widely in nature, but are not readily expressed in most industrially important microorganisms.
"P450 is very important in the synthesis of natural products," said Koffas. "For example, both Taxol, the breast cancer drug that is currently produced from plant cultures, and artemisinin, the anti-malaria drug, have P450 enzymes in their biosynthetic pathways."
The Koffas lab has introduced ways to modify both the P450 monooxygenase enzymes and the host cell, thereby improving their yield of flavonoids.
Microbial biosynthesis methods also are making it easier to create analogs of existing drugs, as well as new molecules for a broad range of therapeutics.
The UB researchers are particularly interested in developing novel molecules that can be used to treat chronic diseases, such as type II diabetes and obesity.
They also are using the methods to produce specialty compounds, such as natural pigments, that could replace chemical dyes in food.
Koffas' goal is to employ these microbial synthesis methods for a wide variety of applications.
Flavonoids, which are of interest to pharmaceutical companies because of their antioxidant and anti-carcinogenic properties, are difficult to produce using currently available methods.
Microbial synthesis strategies also are being adapted by the UB researchers for the biosynthesis of other commercially significant classes of compounds, including vitamins, anti-cancer drugs, anti-parasitic drugs, dyes and food supplements.
The UB group is working on boosting yields further and hopes to achieve pilot scale production of flavonoids by the end of this year.
For further information on commercialization of this technology, please contact Mike Fowler, commercialization manager for bioinformatics and health sciences, in UB's Office of Science, Technology Transfer and Economic Outreach (STOR) at mlfowler@buffalo.edu.
For information on commercialization of SBIR-funded research on the biosynthesis of isoflavonoids, please contact Jack Daiss, technical director, First Wave Technologies at jack@firstwavetechnologies.com.
Koffas's research has received funding from the National Science Foundation, UB's New York State Center of Excellence in Bioinformatics and Life Sciences and the Independent Research and Development Fund of the UB Office of the Vice President of Research.
The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. UB's more than 27,000 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 by Brian Bell @ 7:17 AM
