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UConn Innovation Fund Provides First Round Funding to Three Biotech Startups

Storrs, Conn. – April 20, 2017The University of Connecticut, in partnership with Connecticut Innovations (CI) and Webster Bank, today announced first round funding to three startups through the UConn Innovation Fund. The $1.5 million UConn Innovation Fund was established to provide early-stage financial support to new business startups affiliated with UConn.

The UConn Innovation Fund provides investments of up to $100,000 to companies founded by students, faculty members, and alumni of the university with an in-state business startup tied to research, advanced technologies, or innovations developed at UConn.

The companies receiving first-round funding are:

  • Torigen Pharmaceuticals, Inc. is a startup housed in UConn’s Technology Incubation Program (TIP) that is focused on providing veterinary cancer care solutions for companion animals using the animals’ existing tumor cells to fight the disease.
  • Bioarray Genetics, Inc. is a molecular diagnostics company focused on changing the way that cancer patients are evaluated and treated with tests that predict patient response to cancer treatments. Bioarray is housed at UConn’s Technology Incubation Program facility at UConn Health in Farmington.
  • Shoreline Biome, LLC. is another UConn TIP company that is focused on understanding how the human microbiome functions across the entire landscape of human health and disease.

“In the first round of funding, we identified three exceptional companies that all have ties to the university,” said Jeff Seemann, vice president for research at UConn. “UConn continues to be a center of innovation, and we look forward to supporting and catalyzing more promising startups in the future to continue to create new companies, new jobs, and economic growth in the state.”

The UConn Innovation Fund serves as a critical early-stage revenue stream for in-state business startups that will allow them to stay in Connecticut and grow. The fund’s investors review a company’s strength and existing resources, innovative technology, potential for commercialization, and likelihood of obtaining additional external funding among other factors. All investment decisions are made by a unanimous vote from UConn, CI, and Webster Bank.

“We look forward to supporting these startups with the resources to help them bring their products closer to commercialization,” said Matt McCooe, CEO of Connecticut Innovations. “We know how difficult it can be to grow a company at the earliest stages of development and this funding can help companies overcome some of those first hurdles.”

The fund is managed by the UConn Evaluation Board, fund managers, and an investment committee comprised of representatives from UConn, CI, and Webster Bank. The fund permits Connecticut Innovations—the leading source of financing and ongoing support for Connecticut’s innovative, growing companies—to continue its support of new business startups established through UConn. Webster Bank provides the key financial and banking expertise needed to help new companies grow.

“We are pleased to support Connecticut-based entrepreneurs in their efforts to bring exciting biotech innovations to market,” said Peter Hicks, senior vice president of the emerging growth banking group at Webster Bank.

The next deadline for applications is July 14, 2017.  Businesses interested in learning more about the fund should go to:


About the University of Connecticut
The University of Connecticut is one of the top 25 public research universities in the nation and is a research leader in the fields of advanced materials, additive manufacturing, biomedical devices, cybersecurity, energy, life sciences, sensors, and nanotechnology.  As Connecticut’s flagship institution of higher education, UConn serves as an important resource for Connecticut economic development and is dedicated to building collaborations with industry and entrepreneurs. To learn more, visit

About Connecticut Innovations
Connecticut Innovations (CI) is the leading source of financing and ongoing support for Connecticut’s innovative, growing companies. CI provides venture capital and strategic support for early-stage technology companies; grants that support innovation and collaboration; and connections to its well-established network of partners and professionals. For more information, please visit

About Webster Bank
Webster Financial Corporation is the holding company for Webster Bank, National Association. With $26.1 billion in assets, Webster provides business and consumer banking, mortgage, financial planning, trust, and investment services through 168 banking centers and 349 ATMs. Webster also provides mobile and Internet banking. Webster Bank owns the asset-based lending firm Webster Business Credit Corporation; the equipment finance firm Webster Capital Finance Corporation; and HSA Bank, a division of Webster Bank, which provides health savings account trustee and administrative services. Webster Bank is a member of the FDIC and an equal housing lender. For more information about Webster, including past press releases and the latest annual report, visit the Webster website at

UConn Incubator Companies Raise $39.9 Million in 2016

Farmington, Conn. – April 17, 2017 – The University of Connecticut, today announced record growth in 2016 for the University’s Technology Incubation Program (TIP). TIP was established in 2004 to accelerate the growth of technology-based startups with a strong connection to the University of Connecticut.

TIP companies raised record investments in 2016. Last year TIP startups attracted a record $39.9 million in debt and equity to accelerate the growth of their operations. This is $15.5 million more than the previous record set in 2014.

TIP facility in Farmington, CT at UConn Health

TIP facility in Farmington, CT at UConn Health (UConn Photo/J. Gelineau)

Under the umbrella of UConn’s Office of the Vice President for Research, TIP supports UConn startups as well as innovative external technology ventures. Outside startups conduct R&D activities in Connecticut and benefit from UConn’s research infrastructure, specialized equipment, customized business support services and talent pool.

“The unprecedented state support from Gov. Dannel P. Malloy for the Bioscience CT initiative is bearing fruit in the University of Connecticut Technology Incubation Program,” said Jeff Seemann, Ph.D., UConn/UConn Health vice president for research. “Instead of going to Boston or New York, these companies choose to stay in Connecticut to grow their companies, create jobs, and benefit society with their cutting-edge advances.”

Several TIP companies raised significant investments from debt and equity in 2016, contributing to the program’s record setting total.

Agrivida, an agritech company focused on animal nutrition, had the most substantial raise with $21 million in Series E funding. The funds will be used to advance the commercialization of Agrivida’s patented GRAINZYME® feed additive enzymes for use with poultry and swine, and to support product development for dairy and beef cattle.

“Being a part of UConn’s incubator has helped us meet significant milestones for our company,” said Dan Meagher, CEO of Agrivida. “We are looking forward to delivering on our promise to improve the production efficiency of meat, milk, and eggs to help address the growing global demand for food.”

Frequency Therapeutics successfully raised $9.1 million in 2016, and recently announced a $32 million Series A financing, to continue developing a drug-based therapy to restore hearing in individuals with hearing loss caused by continuous exposure to loud noises. Frequency is applying its proprietary platform, called Progenitor Cell Activation (PCA™), to regenerate inner ear sensory hair cells, which detect sound and transmit signals to the brain. Per the World Health Organization (WHO), 360 million people worldwide have moderate or worse hearing loss, with an additional 1.1 billion people at risk for hearing loss from recreational noise alone.

“Frequency’s scientific team, based at TIP at UConn Health, played an important role in supporting the development of the company’s PCA platform to restore healthy tissue in the body,” said Bob Langer, Ph.D., the David H. Koch Institute Professor at the Massachusetts Institute of Technology and co-founder of Frequency Therapeutics. “We greatly appreciate the ongoing support from TIP as Frequency advances its program for chronic noise-induced hearing loss and looks to expand into additional therapeutic indications.”

Diameter Health, a healthcare software company that helps providers analyze data from their electronic health records more effectively, raised $2.3 million; and CaroGen Corporation, an emerging vaccine immunotherapy company, raised $2 million.

UConn researchers working in the lab

Kepeng Wang, assistant professor of immunology, right, with Kasandra Rodriguez, a research associate at CaroGen Corporation’s technology incubation lab in Farmington on Dec. 12, 2016. (Peter Morenus/UConn Photo)

According to Bijan Almassian, CEO of CaroGen Corporation, the TIP location provides a beneficial vantage point to meet and acquire the talent and expertise needed to conduct R&D operations to grow his company. “The powerful combination of faculty expertise, student and graduate hires, and seasoned industry scientists from across the state give us access to the full array of capabilities that are enabling our progress,” Almassian said.

UConn’s Technology Incubation Program continues to outperform other technology incubators, both in Connecticut and nationally. According to the latest National Business Incubation Association survey data, in 2016 UConn’s incubator was 12,000 square feet larger and housed 62% more startups than that national average. TIP companies raised $39.5 million dollars more in capital investments than the Connecticut average, as reported in the latest Connecticut Business Incubator Network survey.

“TIP is an established program in Connecticut that is known to improve the likelihood of startup success,” said Mostafa Analoui, Ph.D., executive director of venture development and TIP at UConn. “We are pleased with the growth we experienced in 2016, and hope to keep up this momentum.”

Analoui was hired in last year to lead UConn’s efforts to identify disruptive technologies that are ripe for venture development, recruit entrepreneurs and talent to lead these startups, and raise early-stage and follow-on funding to grow these companies.

In January 2016, a $19 million expansion at the TIP facility in Farmington at UConn Health was completed. Paid for through the state of Connecticut’s landmark Bioscience CT initiative, the addition increased total square footage by 20,000 square feet. The program now boasts over 32,000 square feet of high-tech wet labs and office space at its two major locations in Storrs and Farmington.

The extra space has allowed TIP to accept more technology startups into the program. In 2016, TIP was home to 33 companies – the most in the program’s history.

TIP companies contributed to economic development in the state through increased job creation. At the end of 2016, TIP companies employed 71 full-time and 30 part-time employees. This compares with the state average of 27 full- and part-time employees at other incubators in Connecticut.

More than 85 startup companies have been supported through TIP since it was established in 2004. These companies have raised more than $50 million in grant funding, $80 million in debt and equity, and more than $45 million in revenue during that time.

For more information about the UConn Technology Incubation Program, call 860-679-3992 or visit


Jessica McBride
Office of the Vice President for Research

Is Sitting the New Smoking?

People who sit throughout the day are likely at increased risk for disease and death. Recent studies estimate that physical inactivity contributes to more than 300,000 deaths annually in the United States.

Further, the World Health Organization lists physical inactivity as the fourth leading cause of non-communicable disease. These findings have left many who work in sedentary jobs wondering whether they need to cut down on sitting at work to protect and improve their health. Although the research is ongoing, it appears that sedentary workers can benefit from alternating between sitting and standing throughout the day.

One way to accomplish that is by using a sit-stand workstation. Evidence suggests that workers who use sit-stand workstations may experience improved health. For instance, participants in some studies experienced reduced back pain and cholesterol levels and better glucose regulation. In addition, sit-stand workstations don’t seem to hinder productivity, and people generally like using them.

Balance Is Best
When it comes to sitting versus standing at work, striking a balance is the key. In other words, too much standing can be just as harmful as too much sitting. Standing has been associated with lower back pain, leg pain and discomfort, fatigue, varicose veins, chronic venous insufficiency, and a worse prognosis after a diagnosis of coronary artery disease.

Here are some suggestions that aim to balance the risks and benefits of sitting and standing:

Alternate between sitting, standing, and moving every hour.
Use an approximately 3:1 ratio of sitting to standing (sit three times longer than stand).
Incorporate three to five minutes of movement into every hour (standing alone is not enough).
Use adjustable furniture to maintain neutral postures during computer work in all positions. (A neutral posture occurs when muscles are at resting length, joints are naturally aligned, and the spine is not twisted.)

Move It
Sit-stand workstations are not the only option for those looking to counteract the effects of a sedentary workday. Workers can gain many of the same benefits by taking three-to-five-minute “movement” breaks from sitting every hour.

Suggestions for incorporating movement into the workday include:

Walking to a printer or bathroom farther away than the ones you normally use;
Talking with a colleague in person, rather than sending an email or text;
Taking the stairs instead of the elevator;
Holding walking meetings;
Starting a group stretching or exercise class.

Size Matters for Drug Particles

April 13, 2017 – Bret Eckhardt – UConn Communications, and Colin Poitras – UConn Communications
A UConn engineering professor has uncovered new information about how particles behave in our bloodstream, an important advancement that could help pharmaceutical scientists develop more effective cancer drugs.

Making sure cancer medications reach the leaky blood vessels surrounding most tumor sites is one of the critical aspects of treatment and drug delivery. While surface chemistry, molecular interactions, and other factors come into play once drug-carrying particles arrive at a tumor, therapeutic medication doesn’t do very much good if it never reaches its intended target.

Anson Ma, assistant professor of chemical and biomolecular engineering, used a microfluidic channel device to observe, track, and measure how individual particles behaved in a simulated blood vessel.

Ma says he wanted to learn more about the physics influencing a particle’s behavior as it travels in our blood and to determine which particle size might be the most effective for delivering drugs to their targets. His experimental findings mark the first time such quantitative data has been gathered. The study appears in the Biophysical Journal.

“Even before particles reach a target site, you have to worry about what is going to happen with them after they get injected into the bloodstream,” Ma says. “Are they going to clump together? How are they going to move around? Are they going to get swept away and flushed out of our bodies?”

Using a high-powered fluorescence microscope in UConn’s Complex Fluids Lab, Ma was able to see particles moving in the simulated blood vessel in what could be described as a vascular Running of the Bulls. Red blood cells race through the middle of the channel as the particles – highlighted under the fluorescent light – get carried along in the rush, bumping and bouncing off the blood cells until they are pushed to open spaces – called the cell-free layer – along the vessel’s walls.

What Ma found was that larger particles – the optimum size appeared to be about 2 microns – were most likely to get pushed to the cell-free layer, where their chances of carrying medication into a tumor site are greatest. The research team also determined that 2 microns was the largest size that should be used if particles are going to have any chance of going through the leaky blood vessel walls into the tumor site.

“When it comes to using particles for the delivery of cancer drugs, size matters,” Ma says. “When you have a bigger particle, the chance of it bumping into blood cells is much higher, there are a lot more collisions, and they tend to get pushed to the blood vessel walls.”

The results were somewhat surprising. In preparing their hypothesis, the research team estimated that smaller particles were probably the most effective since they would move the most in collisions with blood cells, much like what happens when a small ball bounces off a larger one. But just the opposite proved true. The smaller particles appeared to skirt through the mass of moving blood cells and were less likely to experience the “trampoline” effect and get bounced to the cell-free layer, says Ma.

Ma proposed the study after talking to a UConn pharmaceutical scientist about drug development at a campus event five years ago.

“We had a great conversation about how drugs are made and then I asked, ‘But how can you be sure where the particles go?’” Ma recalls, laughing. “I’m an engineer. That’s how we think. I was curious. This was an engineering question. So I said, ‘Let’s write a proposal!’”

The proposal was funded by the National Science Foundation’s Early-concept Grants for Exploratory Research or EAGER program, which supports exploratory work in its early stages on untested, but potentially transformative, research ideas or approaches.

Knowing how particles behave in our circulatory system should help improve targeted drug delivery, Ma says, which in turn will further reduce the toxic side effects caused by potent cancer drugs missing their target and impacting the body’s healthy tissue.

The findings were particularly meaningful for Ma, who lost two of his grandparents to cancer and who has long wanted to contribute to cancer research in a meaningful way as an engineer.

Measuring how particles of different sizes move in the bloodstream may also be beneficial in bioimaging, where scientists and doctors want to keep particles circulating in the bloodstream long enough for imaging to occur. In that case, smaller particles would be better, says Ma.

Moving forward, Ma would like to explore other aspects of particle flow in our circulatory system, such as how particles behave when they pass through a constricted area, such as from a blood vessel to a capillary. Capillaries are only about 7 microns in diameter. The average human hair is 100 microns. Ma says he would like to know how that constricted space might impact particle flow or the ability of particles to accumulate near the vessel walls.

“We have all of this complex geometry in our bodies,” says Ma. “Most people just assume there is no impact when a particle moves from a bigger channel to a smaller channel because they haven’t quantified it. Our plan is to do some experiments to look at this more carefully, building on the work that we just published.”

Joining Ma on the current study were Ph.D. candidate Erik Carboni; Brice Bognet from UConn’s polymer program in the Institute of Materials Science; chemical and biomolecular engineering associate professor Leslie Shor; Ph.D. students Grant Bouchillon and Andrea Kadilak; and undergraduate student Michael Ward.

UConn Scientists Develop New Antibody for Bowel Disease

April 10, 2017 – Jessica McBride, Office of the Vice President for Research

Molecular and cell biology professor Michael Lynes with lab manager Clare Melchiorre. (Taylor Hudak '18 (CLAS, ED)/UConn Photo)

Molecular and cell biologist Michael Lynes and an international team of researchers have developed a novel antibody designed to prevent the patient’s immune system from attacking its own body. Lynes is shown here with lab manager Clare Melchiorre. (Taylor Hudak ’18 (CLAS, ED)/UConn Photo)

UConn molecular and cell biologist Michael Lynes and an international team of researchers have been awarded a patent for a novel antibody therapeutic that may prove to be safer in the treatment of Inflammatory Bowel Disease (IBD) than other antibodies currently available.

Existing antibody treatments for IBD are ineffective in some IBD patients and pose a risk to the normal functioning of the immune system.

The new antibody, co-invented by the UConn researchers together with a team from Ghent University in Belgium, is designed to prevent the patient’s immune system from attacking its own body and potentially causing irreversible damage.

More than 1.6 million Americans have IBD. Two of the most common forms of IBD are Crohn’s disease and ulcerative colitis, chronic but treatable conditions that affect children and adults. One in 10 people with IBD are under 18, according to the Crohn’s & Colitis Foundation.

More than a decade ago, Lynes, professor and head of the Department of Molecular and Cell Biology at UConn, and his research team discovered a novel and important role that a protein called metallothionein (MT) plays in influencing the body’s immune function. The body produces MT when cells are under stress, and extended periods of stress cause MT to be released from the cells that produced it, Lynes says. MT is an unusual protein that holds onto chemicals in the body – both those that are beneficial, such as zinc and copper, and those that are harmful – such as cadmium and mercury.
Sadikshya Bhandari, a Ph.D. student in molecular and cell biology, in Professor Michael Lynes’ lab. (Taylor Hudak ’18 (CLAS, ED)/UConn Photo)
Sadikshya Bhandari, a Ph.D. student in molecular and cell biology, is reconstituting a chemoattractant to set up a chemotaxis experiment. (Taylor Hudak ’18 (CLAS, ED)/UConn Photo)

While studying MT, Lynes and his research team noticed that MT released from cells could mimic some of the signals that the immune system uses as cues to tell cells to go to one place or another in the body. Under normal circumstances, immune cells use these signals to guide them to local infections or other tissue damage. When cells are stressed over prolonged periods, this can mean that there is persistent inflammation accompanied by damage to nearby healthy tissue.

About 50 million people, or 20 percent of the U.S. population, suffer from some form of autoimmune disease or chronic inflammation, according to the American Autoimmune Related Diseases Association. More than 80 autoimmune diseases have been identified, and autoimmune diseases are becoming increasingly prevalent, for reasons unknown, according to the National Institute of Environmental Health Sciences. While causes of autoimmune diseases also remain largely unknown, scientific consensus is that autoimmune diseases are probably triggered by a combination of genetic and environmental factors.

A team of Belgium doctors and scientists studying IBD had published a paper saying that their sickest patients were those whose bodies produced the most MT. The MT protein, which serves as a normal part of the cell’s internal machinery inside the cell, was getting outside the cell and causing damage. That paper by Dr. Martine DeVos, Debby Laukens, and Lindsey Devisscher led to a collaboration with Lynes.

Since the protein serves an essential purpose, researchers can’t shut it off all together; so they had to find a way to stop MT from prolonging inflammation and damaging healthy cells. Lynes and his team produced an antibody protein that basically attaches itself to MT when it is outside the cell and inactivates it – preventing the body from attacking its intestinal system. This approach dramatically reduced IBD in mouse models of the human disease.

“It’s like we have created a partner for MT that binds it and hugs it and won’t let it go,” Lynes says.

The UConn team has been testing this treatment on mice, and is working on creating a form of the antibody that their collaborators can test in humans.

Since one form of stress on cells comes from environmental triggers, Lynes and his team have received funding support from the National Institute of Environmental Health Sciences. He and his team have also received funding from UConn and from the state’s quasi-public investment agency, Connecticut Innovations, to commercialize the anti-MT therapeutic. This includes $50,000 from UConn’s SPARK Technology Commercialization Fund, and $500,000 from the Connecticut Bioscience Innovation Fund managed by Connecticut Innovations. He has also worked with the External Advisory Board and received funding for the project from Yale University’s Program in Innovative Therapeutics for Connecticut’s Health (PITCH).

“This is a prime example of cutting-edge research from a UConn lab being translated into a potentially life-changing treatment for patients,” says Jeff Seemann, vice president for research at UConn and UConn Health. “The exciting research being conducted by internationally recognized faculty at UConn is not only important for the scientific community, but also for our citizens and our state’s economy.”

Lynes’ research is significant, because while there is a great deal of research being done to try to keep autoimmune diseases at bay, his work seeks to learn more about the causes. Autoimmune diseases are increasing in both industrialized and developing countries, so his work has strong public health and commercial potential.

Meanwhile, Lynes is also working with Ciencia Inc., an East Hartford-based biotech company, to develop a test that could measure 1,000 different kinds of molecules in a drop of blood to find patterns of molecular biomarkers that can serve as red flags for the early onset of autoimmune disease.

“We are excited about the opportunity presented by Dr. Lynes’ innovative work,” says Arturo Pilar, president of Ciencia. “UConn has been a great partner, and university support for this effort has been critical to the substantial progress made to develop a commercial product.”

Early detection can mean that treatment can begin earlier in the disease, thus improving people’s chance for better health.

“It appears this has the potential to identify someone’s propensity to develop an autoimmune disease, and to enable treatments that are more effective,” Lynes says.

Often, by the time people have symptoms of autoimmune disease that brings them to their doctor, irreparable damage has been done to their bodies. Developing these biomarkers won’t cure the disease, he adds, but will allow for medical intervention early, minimizing the damage.

Nancy Petry: Woman of Innovation

March 30, 2017 – Jessica McBride, Office of the Vice President for Research

Nancy Petry, Ph.D., winner of the Connecticut Technology Council's Women of Innovation Award for Research Innovation and Leadership. (Janine Gelineau/UConn Health Photo).

Nancy Petry, whose research on behavioral treatments for addictive disorders has led to an intervention used with patients throughout the VA system, is this year’s winner of the Connecticut Technology Council’s Women of Innovation Award for Research Innovation and Leadership.

“To be recognized for my work in such a supportive atmosphere by an organization like the Connecticut Technology Council is wonderful” says Petry. “I am honored to have been selected as the 2017 Woman of Innovation from a group of truly remarkable researchers, mentors, and community and business leaders.”

This marks the fourth time in the 13-year history of the Women of Innovation Awards that a member of the UConn Health faculty has been so honored.

Associate professor of reconstructive sciences Liisa Kuhn won in 2009, and Dr. Marja Hurley, professor of medicine and orthopaedic surgery, won in 2010, both in the category of Academic Innovation and Leadership.

“We are thrilled that the Connecticut Technology Council has recognized Dr. Petry – one of UConn Health’s most innovative researchers – for her significant contributions to her field,” said Jeff Seemann, vice president for research at UConn and UConn Health. “Honors such as these speak to the preeminence of research and innovation taking place every day at UConn and UConn Health. This research benefits not only our students and the scientific community, but also the economic health of our state and the physical health of our society.”

Petry says what was most impressive to her about the Women of Innovation Award experience was learning about the achievements of the other innovators she met at the March 29 ceremony.

“What these scientists of all ages have accomplished is really remarkable. From founding green energy startups to developing treatments for brain damage – these women are having an immediate impact in a variety of fields. It is truly inspiring to be in the company of such talented people, regardless of the fact that they are women.”

Since becoming a faculty member at UConn Health in 1996, Petry has been awarded more than $31 million dollars in grants from the National Institutes of Health (NIH). Her research has focused on improving patient adherence across a number of conditions, including some highly stigmatized ones like substance abuse and pathological gambling. This led to one of her most notable achievements – the development of a behavior modification approach to treat addiction that has been widely adopted throughout the U.S., as well as in Europe and Asia.

Much of her research on contingency management treatments for substance use disorders is conducted at community-based treatment centers throughout Connecticut and Massachusetts.

She says she is committed to this work because while drug therapies and medical devices can substantially improve outcomes, patients need to use them as prescribed to have the greatest impact.

“As a scientist, it is exciting to see my research translated into solutions for patients, not only for treating addictions, but also to improve patient adherence for other medical conditions.”

In addition to her work at UConn Health, Petry also serves as a consultant and advisor for the NIH and the Veterans Administration and is the editor-in-chief for Psychology of Addictive Behaviors.

The Connecticut Technology Council Women of Innovation event also honored Jinbo Bi, associate professor of computer science and engineering. Dr. Bi is recognized as a world leader in machine learning, and her discoveries have led to 11 patents. Her research focuses on designing innovative approaches to diagnose complex psychiatric and addictive disorders and to enhance personalized treatment.

Three graduate students from UConn and UConn Health were also honored at the event. Manisha Mishra, a Ph.D. candidate from the Department of Electrical & Computer Engineering, Deborah Dorcemus, a Ph.D. candidate from the Department of Biomedical Engineering, and Jun Chen, a Ph.D. candidate also from the Department of Biomedical Engineering, were all recognized as Women in Innovation Finalists in the Collegian Innovation and Leadership category.

Expert Discusses Only Drug Approved for Progressive MS

March 30, 2017 – Lauren Woods – Schools of Medicine and Dental Medicine

Neurologist Dr. Matthew Tremblay, who specializes in the care of patients with multiple sclerosis at UConn Health, discusses the first drug just approved by the FDA for patients with difficult to treat primary progressive MS.

Q. What is multiple sclerosis?

A. Multiple sclerosis is believed to be an autoimmune disease that results in damaging inflammation of the brain and spinal cord. The damage occurs to a material known as myelin, which coats the axons [projections of nerve cells], allowing signals to conduct rapidly from one part of the nervous system to another.

Q. What are the symptoms of MS and the different types?

A. The most common form of MS, referred to as relapsing-remitting MS, is characterized by episodes or attacks with new neurologic symptoms caused by active inflammation in an area of the brain or spinal cord. The inflammation eventually subsides, allowing spontaneous recovery from symptoms after a period of weeks. Common symptoms of an MS relapse or attack include new numbness, tingling, or weakness in an area of the body, painful loss of vision, vertigo, double vision, and sometimes other less common symptoms. Other chronic symptoms that patients with MS experience can include fatigue, difficulty controlling bladder function, trouble with walking, and/or changes in sleep patterns and mood. A less common type of MS, affecting 10-15 percent of patients, is referred to as primary progressive MS. Unlike relapsing forms of MS, primary progressive MS patients develop chronic symptoms of MS – often gradual weakness and difficulty walking – without experiencing a relapse or attack. The difference between the two forms of MS, and specifically the mechanisms underlying disability progression, are not well understood.

Q. What can you tell us about the newly FDA-approved drug Ocrevus?

A. Ocrevus is a fully humanized monoclonal antibody against the CD20 marker on the surface of most B-cells, a type of lymphocyte responsible for producing antibodies against various pathogens and stimulating T-cells to attack similar pathogens. A similar medication was developed many years ago, called rituximab, which has proven to be successful for treatment of B-cell lymphomas and numerous autoimmune diseases, as well as MS. However, rituximab was only studied in a smaller phase 2 study in both relapsing and progressive MS nearly 10 years ago. Because of the smaller clinical trial, the medication was not considered by the FDA for the treatment of MS. Ocrelizumab was specifically tested in large-scale phase 3 trials for both forms of MS, with excellent efficacy. It will now be the first and only medication approved for the treatment of primary progressive MS.

Q. How does the drug work?

A. Ocrevus works by eliminating most of the B-cells in the body, without removing the stem cells needed to replenish the next generation of B-cells or the antibody-producing plasma cells necessary to maintain immunity from prior vaccinations and infections.

Q. What have studies shown about its effectiveness to help MS patients?

A. The OPERA I and OPERA II clinical trials demonstrated that Ocrevus is superior to an existing MS medication, Interferon beta-1a, for reducing MS relapses, MRI evidence of inflammation (referred to as gadolinium enhancement), and delaying physical disability related to MS. Also, the ORATORIO trial demonstrated that Ocrevus decreased disability progression in patients with primary progressive MS when evaluated at both three-month and six-month intervals, as compared to a placebo. The study also found that patients on Ocrevus were less likely to have reduced walking speed compared to the pre-treatment measurements.

Q. Who is a candidate for the new drug?

A. Ocrevus was proven effective at treating both types of MS in the clinical trials published earlier this year in the New England Journal of Medicine. It is the first treatment to be approved by the FDA for patients with primary progressive MS. However, it is worth noting that the benefit in primary progressive MS may be appreciated mostly in a subset of patients who had evidence of inflammation on MRI studies and were younger in age.

Q. How does this drug change the care paradigm for current and new MS patients?

A. Ocrevus will change the care paradigm in a few ways. First, it will be the only FDA-approved medication for the treatment of primary progressive MS, for which there was previously no proven therapy to prevent disability progression. Second, Ocrevus is an infused medication that would only need to be administered twice a year. Lastly, safety can often be a barrier with MS medications, owing to the fact that they suppress the immune system. Ocrevus demonstrated similar safety to a medication that has been used for well over a decade. MS specialists will likely also draw on the experience with the medications predecessor, rituximab, to infer risks of serious infections.

Mark of Malignancy Identified in Prostate Cancer

March 30, 2017 – Kim Krieger – UConn Communications

More PSMA, more problems. Prostate cells with more prostate-specific membrane antigen (PSMA) have more cancer cells (purple), growing in a more disorganized way, than the open ducts in a prostate whose cells have little PSMA. (Caromile and Shapiro/UConn Health Image)

More PSMA, more problems. Prostate cells with more prostate-specific membrane antigen (PSMA) have more cancer cells (purple), growing in a more disorganized way, than the open ducts in a prostate whose cells have little PSMA. (Caromile and Shapiro/UConn Health Image)

Prostate cancer is the second deadliest cancer in men in the U.S. It kills more than 26,000 men in the country every year. But, as in the case of breast cancer, one prostate cancer will progress rapidly while another tumor will sit for decades and never spread. In the March 14 issue of Science Signaling, UConn Health researchers describe how a well-known protein might reveal whether a tumor is mild-mannered or out to kill.

Researchers have known about prostate-specific membrane antigen (PSMA) for more than 30 years. Yet they weren’t sure what it did. They knew there’s not a lot of PSMA on normal prostate cells, but as the cells become cancerous, growing faster and starting to invade surrounding tissues, more and more PSMA appears on the tumor cells. Recently, two UConn cell biologists, Leslie Caromile and Linda Shapiro, wondered what the PSMA was actually doing. Did it help the cancer cells get worse in some way?
More PSMA, more problems. Prostate cells with more prostate-specific membrane antigen (PSMA, image on the left) have more cancer cells (purple), growing in a more disorganized way than the open ducts in a prostate whose cells have little PSMA (image on the right). (Caromile and Shapiro/UConn Health Image)
More PSMA, more problems. Prostate cells with more prostate-specific membrane antigen (PSMA, image on the left) have more cancer cells (purple), growing in a more disorganized way, than the open ducts in a prostate whose cells have little PSMA (image on the right). (Caromile and Shapiro/UConn Health Image)

To find out, the two researchers at UConn Health bred mice that tend to develop prostate tumors to other mice, that were identical save that some could and some could not make the PSMA protein. The offspring developed prostate tumors either with or without PSMA. The tumors in mice that lacked PSMA were much less aggressive, with a more limited blood supply, than the tumors grown by their PSMA-making siblings. In other words, the PSMA-free tumors were much less cancerous.

The researchers then looked at cell lines developed from human prostate tumors to see if the observation held true for humans as well as mice. They removed the ability to make PSMA from some cells and compared them to their parent cells that still had PSMA. Importantly, the human cells without PSMA acted just the same as the mouse tumor cells lacking PSMA, confirming that PSMA worked the same in lab mice tumors as it did in human prostate tumors.

Caromile and Shapiro then examined databases characterizing over 50 human prostate tumor biopsies. Each biopsy was rated for tumor aggressiveness and how far the cancer had progressed. The researchers found that all of the biopsies rated as more aggressive had more PSMA than the biopsies rated as less aggressive. Some of those were also matched with benign, non-cancerous tissue donated by the same person – and in every case, the benign tissue had little or no PSMA compared with the cancer. It was clear that PSMA is tightly linked to prostate cancer. But why?

“We found that PSMA changes signals inside the cell to make cells grow faster, resist stress better, and survive longer, as well as be less sticky and probably metastasize faster,” says Shapiro. The less that cells stick to one another, the more likely they are to detach from the main tumor and travel around the body to form other tumors. PSMA also appears in other cancers driven by hormones, such as endometrial and breast cancer, as well as in bladder cancer. Caromile and Shapiro’s next set of experiments will explore how PSMA is related to metastasis, the process of cancer spreading throughout the body. It is actually the metastases that are the big killer in prostate cancer, and so finding more about how PSMA regulates their signals would also benefit patients.

Proving that abundant PSMA on a cell’s surface goes hand-in-hand with cancer opens up many new opportunities, Caromile says. PSMA is already used as a target for delivering chemotherapy, but could be a good drug target itself. Because it seems to be activating pathways that make cells cancerous, shutting down PSMA might shut down a cancer. Although using it as a drug target is still far off, it’s a promising lead that could help doctors and patients narrow the uncertainty when deciding how aggressively to treat a tumor. And eventually, it drugs that disarm PSMA could change the very nature of a tumor from a killer to a mere annoyance.

Responding to a Crisis: A Vaccine for Zika

While a new Gallup poll finds most Americans are not worried about Zika, the recent case of an infected baby born in San Diego demonstrates the virus is a very real issue in this country. One UConn scientist has been working on a vaccine for Zika since the news about cases in Brazil first surfaced last year. For Paulo Verardi, the work is both professional and personal – he’s a native of Brazil. And for his lab, creating a vaccine that is both effective and economical is a daily goal.

UConn Joins Hunt for New Materials

Rampi Ramprasad, professor of materials science and engineering, received a grant from the Toyota Research Institute. The project will involve design of functional polymers using advanced quantum mechanical computations and machine learning. Photo taken on March 30, 2017. (Sean Flynn/UConn Photo)

Rampi Ramprasad, professor of materials science and engineering, received a grant from the Toyota Research Institute. The project will involve design of functional polymers using advanced quantum mechanical computations and machine learning. (Sean Flynn/UConn Photo)

The University of Connecticut is one of several leading research institutions collaborating with the Toyota Research Institute to accelerate the design and discovery of advanced materials using artificial intelligence and machine learning.

The Toyota Research Institute (TRI) announced March 30 that it is investing $35 million to support the initiative over the next four years in an effort to revolutionize materials science and identify new advanced battery materials and fuel cell catalysts that can power future zero-emissions and carbon-neutral vehicles.

It is extremely likely there are new and potentially much better functional polymers out there waiting to be discovered. Our goal is to accelerate the discovery process by using virtual screening methods … so that potential new polymers may be identified before they are made.
— Rampi Ramprasad

UConn materials scientist Ramamurthy “Rampi” Ramprasad is leading the effort at UConn. Ramprasad’s lab will work to identify new polymers using quantum mechanical computations and data-driven machine learning. Because of their flexible chemical compositions, polymers are impressive when used as insulators, semiconductors, and permeable membranes. They also are safe, inexpensive to produce, and light. As such, they hold the potential for broader use in energy storage applications such as rechargeable batteries and fuel cells.

“Given the nearly infinite chemical compositions for polymers, it is extremely likely there are new and potentially much better functional polymers out there waiting to be discovered,” says Ramprasad, a professor in the School of Engineering. “Our goal is to accelerate the discovery process by using virtual screening methods powered by advanced computations and machine learning so that potential new polymers may be identified before they are made.”

Other institutions participating in the initiative include Stanford University, the Massachusetts Institute of Technology, the University of Michigan, and the University at Buffalo. The U.K.-based materials science company Ilika is also a research partner, and there may be others. TRI is in ongoing discussions with additional collaborators.

“Toyota recognizes that artificial intelligence is a vital basic technology that can be leveraged across a range of industries, and we are proud to use it to expand the boundaries of materials science,” said TRI Chief Science Officer Eric Krotkov. “Accelerating the pace of materials discovery will help lay the groundwork for the future of clean energy, and bring us even closer to achieving Toyota’s vision of reducing global average new-vehicle CO2 emissions by 90 percent by 2050.”

The research will merge advanced computational materials modeling, new sources of experimental data, machine learning, and artificial intelligence in an effort to speed up the development of new materials, a process that historically has been measured in decades. The institutional research programs will follow parallel paths, working to identify new materials for use in future energy systems as well as to develop tools and processes that can accelerate the design and development of new materials more broadly.

The Toyota Research Institute is focusing on three key areas as part of the initiative:

• The development of new models and materials for batteries and fuel cells;
• Broader programs to pursue novel uses of machine learning, artificial intelligence, and materials informatics approaches for the design and development of new materials; and
• New automated materials discovery systems that integrate simulation, machine learning, artificial intelligence, and/or robotics.

Ramprasad’s lab has spent the past several years painstakingly building an online polymer genome knowledge base for a data vault the research team created called Khazana. The Khazana platform, which is publicly accessible, allows scientists to search for potential polymers with specific properties. Polymers are large molecules made up of many repeating chemical building blocks. A common example of a polymer type is plastics, which can be chemically altered and easily manufactured for a variety of different applications from soda bottles to deck chairs to garbage bags.
UConn Professor Rampi Ramprasad is using advanced computing and machine learning to search for new polymers as part of a research project with the Toyota Research Institute. Because of their flexible chemical compositions, polymers hold great potential for use in energy storage applications such as high density capacitors. (Rampi Ramprasad/UConn Graphic)
UConn Professor Rampi Ramprasad is using advanced computing and machine learning to search for new polymers as part of a research project with the Toyota Research Institute. Because of their flexible chemical compositions, polymers hold great potential for use in energy storage applications such as high density capacitors. (Rampi Ramprasad/UConn Graphic)

The novel computational method created by Ramprasad’s research team applies basic quantum mechanics to calculate the atomic and electronic structures of different polymers. This information is then used to “train” a machine learning model to make ultra-fast predictions of properties of new polymers. The machine learning model recognizes polymers based on their numerical representations or “fingerprints.” With this approach, materials scientists can quickly predict the electronic properties of a new polymer, such as its band gap (the amount of energy it takes for an electron to break free of its home atom in the polymer), and its dielectric constant (a measure of the effect an electrical field has on the polymer). Those bits of information, and other relevant information that will be incorporated into the system as part of the TRI initiative, are crucial to scientists looking to create new materials that will improve electrochemical energy storage devices like fuel cells and batteries.

Accelerating materials science discovery represents one of four core focus areas for TRI, which was launched in 2015 with mandates to also enhance auto safety with automated technologies, increase access to mobility for those who otherwise cannot drive, and help translate outdoor mobility technology into products for indoor mobility.