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Andrew Shubin receives commendation for PhD Dissertation

Tuesday, May 23, 2017

Andrew Shubin

Andrew Shubin

Andrew Shubin, a 2017 PhD graduate in the lab of Professor Danielle Benoit, has been selected to receive commendation in the Outstanding Dissertation Award Competition for Engineering. Andrew's PhD research project is titled, "Poly(ethylene glycol) Hydrogels for Salivary Gland Regeneration.”

Abstract: 
Over 500,000 people worldwide are diagnosed with head and neck cancers yearly.  Radiation, a mainstay of curative therapy, causes irreparable damage to the salivary gland acinar cells, which results in chronic dry mouth or xerostomia.  Xerostomia negatively affects patient quality of life for which no current treatments can ameliorate.  Recently, regenerative therapies utilizing the direct injection of primary submandibular gland (SMG) cells into irradiated salivary glands have shown promise in regenerating salivary gland tissues and partially restoring gland function.  However, the amount of regeneration is variable and the little is known about the mechanism of healing and the characteristics of primary SMG cells.  To address these limitations we propose the use of poly(ethylene glycol) (PEG) hydrogels to enhance in vitro culture conditions and in vivo cellular transplantation.  PEG is a “bio-inert” polymer which provides “blank-slate” to control and study specific cell-material interactions.  Initial work focused on designing cytocompatible methods to encapsulate and culture primary SMG cells within PEG hydrogels.  The minimization of radicals using thiol-ene versus methacrylate-based chain polymerizations of hydrogel macromers and the inclusion of cell-cell interactions through the formation of multicellular “spheres” supported the survival and proliferation of primary SMG cells within PEG hydrogels for a 14 day culture period.   Genetic lineage tracing was employed to determine the in vivo origin of encapsulated cells and showed that the majority (>80%) of encapsulated cells come from acinar and duct populations.  To improve PEG hydrogels as a tissue engineering platform, the effects of laminin incorporation and different forms of hydrogel degradation on the proliferation, development of acinar cell phenotypes, and epithelial morphogenesis of encapsulated SMG cells were explored.  The encapsulation of SMG cells within enzymatically (e.g., via cell-dictated processes) degradable hydrogels resulted in increased expression of the acinar water channel Aquaporin-5 (AQP5) and cellular organization reminiscent of native gland tissue compared to SMG cells encapsulated in hydrogels with bulk-hydrolytic degradability.  Degradable hydrogels (either hydrolytic or enzymatic) supported the greatest amount of cellular proliferation versus non-degradable gels.  PEG hydrogels were further utilized to study cells originating from acinar tissues in primary culture.  Despite previous studies suggesting otherwise, genetic lineage tracing showed that acinar lineage cells compose a significant portion of primary SMG cells in culture.  However, acinar lineage cells underwent significant changes in morphology and exhibited a ~100-fold decrease in expression of the acinar cell markers AQP5 and Mist1.  Furthermore, many acinar-lineage cells express cytokeratins and proliferate, indicating a transition to a duct-cell like phenotype. This acinar cell plasticity has important underpinnings for salivary gland biology and tissue engineering as acinar cells are the most prevalent cell type in the salivary gland.  Finally, in vivo methods of hydrogel mediated cell transplantation were developed, but caused sufficient mortality with irradiation.  Similar in vivo methods were well tolerated with minimal mortality in non-irradiated mice, suggesting that irradiation substantially affects surgical survival.  Taken together, this work demonstrates the utility of PEG hydrogels in characterization primary SMG cells and highlights several future areas of inquiry.

Marian Ackun-Farmmer wins newly established ASE Barnard Fellowship

Friday, April 28, 2017

Photo of Marian

Marian Ackun-Farmmer

Marian Ackun-Farmmer of the Benoit Lab has been selected for one of the newly established Arts, Sciences and Engineering Donald M. and Janet C. Barnard Fellowships. Marian was recognized specifically for her strong research record as well as her commitment to mentoring, outreach and service to the Department of Biomedical Engineering as well as her field. The fellowship comes with a $3K stipend top-off for the 2017-2018 academic year, as well as a tuition award. Congratulations, Marian!

Danielle Benoit is Rochester's 'Young Engineer of the Year'

Friday, April 7, 2017

Benoit in the lab

Danielle Benoit, recipient of the Young Engineer of the Year
award from the Rochester Engineering Society, in her lab with
PhD students Yuchen Wang and Maureen Newman.
(Photos by J. Adam Fenster/University of Rochester).

Each year, Danielle Benoit leaves her Therapeutic Biomaterials Lab at the University of Rochester to host the Annual Benoit Laboratory Lemonade Stand at the Rochester and Brighton public markets.

Benoit and her students serve lemonade and explain their work on childhood cancer therapies as part of a national effort organized by Alex’s Lemonade Stand Foundation, which has helped fund her research.

“Most people don’t realize that treating cancer in children is much different from treating cancer in adults,” says Benoit, an assistant professor of biomedical engineering. “At the same time, funding for childhood cancer research is woefully miniscule, compared to the money that goes into studying adult cancers.”

Benoit’s community outreach is one reason she is the recipient of the 2016 Young Engineer of the Year Award from the Rochester Engineering Society. The award recognizes outstanding achievement in and contributions to the profession by young engineers in the Rochester region and promotes the importance of engineering practice to society.

Benoit, who joined the University in 2010, is an international leader in developing therapeutic biomaterials with applications in bone and salivary gland regeneration and treating dental caries and childhood cancers.

“Her work is creative, and transformative,” says Diane Dalecki, chair of the Department of Biomedical Engineering. “She is a true and creative engineer, applying principles of classical chemical engineering and materials science to new biomedical applications in medicine.”

This has resulted in numerous patents; several federal, state, foundation and industry grants – including a prestigious National Science Foundation Faculty Early Career Development (CAREER) Award -- and such professional awards as the 2015 Young Innovator Award in Cellular and Molecular Bioengineering.

Benoit also is “an outstanding educator, dedicated to training the next generation of engineers,” Dalecki says. Benoit teaches a core biomaterials course for undergraduates and courses in biomaterials and drug delivery for graduate students. She annually mentors students working on senior design projects and undergraduates who participate as Xerox fellows in a summer research program.

Benoit with Students

Benoit demonstrates the properties of fluids to
elementary school students visiting her lab.

"Danielle is an outstanding faculty member, whose research in new biomaterials will have a large impact on therapeutics for a number of diseases and whose teaching and service demonstrate her dedication to the educational and outreach missions of the Hajim School," says Wendi Heinzelman, dean of the school.

Benoit's community outreach also includes inviting an elementary school class to her laboratory each year for a day of learning and hands-on experimentation. “Importantly, Dr. Benoit always involves her whole lab in these events, thereby instilling the importance of community outreach to the next generation of engineers in training,” Dalecki says.

Fifth graders visit Benoit Lab for demonstration and hands-on testing

Tuesday, April 4, 2017

benoit lab

A local entrepreneur club comprised of fifth graders interested in science and the business aspects of science recently contacted the Benoit lab after conducting one of the outreach experiments the lab shared online. The module demonstrates diffusive drug delivery through hydrogels, and they were interested in conducting another hands-on demonstration alongside the scientists behind the activity. Professor Benoit invited them to the Benoit Lab, where they met with lab members, took a mini tour, attended a presentation on hydrogel mechanics, and did some hands-on mechanical testing of hydrogels. The takeaway: gels made with lower weight percents are softer, and gels made with higher weight percents are stiffer, allowing us to tailor hydrogel constructs for our desired tissue engineering applications.

benoit lab

Benoit Lab's Yuchen Wang wins New Investigator Recognition Award

Monday, April 3, 2017

benoit lab

Yuchen Wang, a graduate student in the lab of Professor Danielle Benoit, has won a New Investigator Recognition Award. Yuchen was presented with the award at the Orthopaedic Research Society (ORS) Annual Meeting in San Diego, California for her project titled, "Delivery of β-Catenin Agonists via Targeted Nanoparticles to Enhance Fracture Healing". Co-authors for this research were Michael Baranello, Maureen Newman, Tzong-Jen Sheu, J. Edward Puzas and Danielle Benoit.

benoit lab

Marian Ackun-Farmmer receives AfterCollege Engineering Student Scholarship

Thursday, February 9, 2017

student with pipet

Marian Ackun-Farmmer

Marian Ackun-Farmmer, a biomedical engineering student in the lab of Danielle Benoit, is the recipient of an AfterCollege Engineering Student Scholarship. Founded in 1999, AfterCollege, Inc. is an online professional platform that connects students, faculty, alumni and employers through customized career networks at colleges and professional organizations across the country. AfterCollege has awarded more than $1,000,000 in scholarships and student activities through our program to date. Congratulations, Marian!

Read More: Marian Ackun-Farmmer receives AfterCollege Engineering Student Scholarship

Ken Sims of Benoit Lab receives NRSA funding

Monday, February 6, 2017

Sims

Ken Sims

Ken Sims, a PhD student working in the lab of Danielle Benoit, has received funding from the Ruth L. Kirschstein National Research Service Award (RRSA) Individual Predoctoral Fellowship program (F31).

His project is titled, "Engineered pH-Responsive Nanoparticle Drug Delivery to Inhibit Oral Biofilm Formation," and addresses the issue of tooth decay, which affects over two-thirds of children and nearly all adults worldwide and results in billions of dollars of direct and indirect healthcare costs each year. Most current treatment options involve topically applied drugs that provide little to no protection against tooth decay. The study will focus on designing a drug delivery system capable of penetrating dental plaque and releasing antibacterial drugs specifically where cavities develop: the acid covered tooth enamel surface. This research may lead to a new promising, clinically relevant therapeutic approach to prevent tooth decay and other oral diseases.

Read More: Ken Sims of Benoit Lab receives NRSA funding

Teamwork toward a ‘Perfect Bullet’ for Leukemia

Wednesday, January 25, 2017

journal cover

Imagine that a drug is “oil” and the human body is “water.” A conduit would be needed to steer cancer drugs through the body to selectively target cancer cells, wherever they reside.

If a budding Wilmot Cancer Institute investigation pans out, a nanoparticle-based delivery system might be exactly the conduit that scientists have been looking for, the trio of young researchers say.

Danielle Benoit, Ph.D., associate professor in the Department of Biomedical Engineering, Rudi Fasan, Ph.D., associate professor of Chemistry, and Ben Frisch, Ph.D., a research assistant professor in the Department of Medicine, Hematology/Oncology, are working together to improve the treatment of acute myeloid leukemia (AML), one of the deadliest types of blood cancers because it often relapses after initial therapy.

They each bring a different scientific discipline and a distinct role to the project. Fasan develops new drugs and new methods to make them more effective. In this case, he discovered and modified a small-molecule anti-cancer drug derived from a natural plant source related to the magnolia tree. After testing several different chemical forms of the compound, he is studying the correct potency and ability to precisely destroy cancer cells.

Professor Benoit’s nano-delivery system can transcend the barriers that sometimes prevent drugs from reaching their target. Nanoparticles are microscopic materials that act as a bridge between different structures—in this case the nanoparticles are designed to encapsulate an oily drug compound and make it more compatible with the body’s water. Her system also packages the drug with peptides (amino acids) that direct the treatment into the bone marrow, where leukemia takes root.

Getting to the root of the disease is important. Years ago, scientists discovered that leukemia most likely relapses because a subset of cells, known as leukemia stem cells, can dodge standard chemotherapy. Mature leukemia stem cells hide in the bone marrow in a quiet state, until they resurge. Wiping out these stem cells is the key to improving the treatment for a disease that can be very aggressive.

So far, scientists have not been able to target leukemia stem cells directly in the bone marrow, says Frisch, who studies the bone marrow environment for clues as to why blood cancers flourish there. His role is to take Fasan’s new drug, which will be loaded into Benoit’s nano-delivery system, and conduct experiments in cell cultures and mice to find out if the system is effective at binding to cancer cells.

“By using the proper materials to enhance drug delivery,” Benoit adds, “it could potentially revolutionize cancer treatment.”

journal cover

The team won a 2016-17 University Research Award. Funded annually by UR President Joel Seligman, the money goes to scientists with projects that have a high probability of receiving additional external funding. They received $75,000 to generate data to compete for larger grants from the National Cancer Institute, the Leukemia and Lymphoma Society, and the Leukemia Research Foundation.

“The idea is to have a perfect bullet,” Fasan says. “A very nice feature of this collaboration is that we can take advantage of complementary expertise and run with it.”

This article was originally published in Dialogue, the Wilmot Cancer Institute magazine.

Read More: Teamwork toward a ‘Perfect Bullet’ for Leukemia

University of Rochester cohosts 2017 Mid-Atlantic Region Biomaterials Day

Tuesday, January 3, 2017

The University of Rochester is joining with City College of New York, Columbia University, Johns Hopkins University, University of Rochester, and Rutgers University to host the 2017 Mid-Atlantic Biomaterials Day on February 24 in New York City.

The theme for the conference this year is "Biomaterial Frontiers: Emerging challenges creating new opportunities." This all-day research conference will feature local faculty, student, and industry speakers and is designed to provide networking opportunities and foster new collaborations.

Professor Danielle Benoit will be speaking on drug/gene delivery at the conference along with other professors with research focusing on biomaterials. The University of Rochester is now accepting abstracts for rapid fire talks and posters, with a due date of January 27. To submit an abstract or to register, please visit The Biomaterials Day page and please view the Biomaterials Day Flyer

Read More: University of Rochester cohosts 2017 Mid-Atlantic Region Biomaterials Day