Inherited Variations in Drug and Neurotransmitter Metabolism" Dr. Weinshilboum's research has focussed on pharmacogenetics and pharmacogenomics,.
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Classic: Weinshilboum: Inherited Variations in Drug and Neurotransmitter Metabolism 1981 - Video
India joins genome club -Genomics in India, News, First INdian genome sequence, Pharmacogenomics, Genomics, India, Science, Indian genome research
Pharmacogenomic analyses have become a key part of state-of-the-art drug trials, but the pharmaceutical companies funding and organizing those trials have often been stymied in collecting and using genetic specimens from study participants. Dr.
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Drug Firms Want More Access to Genetic Specimens - Video
Original Article
The Pharmacogenomics Journal advance online publication 20 July 2010; doi: 10.1038/tpj.2010.60
F Han1,4, H Yu1,4, C Tian1, H E Chen1, C Benedict-Alderfer1, Y Zheng1, Q Wang1,5, X Han1 and Q Y Zheng1,2,3
1. Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH, USA
2. Department of Genetics, Case Western Reserve University, Cleveland, OH, USA
3. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA
Correspondence: Dr QY Zheng, Department of Otolaryngology-HNS, Case Western Reserve University, 11100 Euclid Avenue, LKS 5045, Cleveland, OH 44106, USA. E-mail: qing.zheng@case.edu
4These authors contributed equally to this work.
5Current address: Department of Otolaryngology and HNS, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853 China.
Received 4 November 2009; Revised 4 June 2010; Accepted 14 June 2010; Published online 20 July 2010.
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Abstract
We report a novel mutation (erlong, erl) of the cadherin 23 (Cdh23) gene in a mouse model for DFNB12 characterized by progressive hearing loss beginning from postnatal day 27 (P27). Genetic and sequencing analysis revealed a 208?T >C transition causing an amino-acid substitution (70S–P). Caspase expression was upregulated in mutant inner ears. Hearing was preserved (up to 35-dB improvement) in pan-caspase inhibitor Z-VAD-FMK-treated mutants compared with untreated mutants (P<0.05). Outer hair cell (OHC) loss in the cochleae of Z-VAD-FMK-treated mutants was significantly reduced compared with those of untreated mice. Thus, the erl mutation can lead to hearing loss through apoptosis. This is the first genetic mouse model of hearing loss shown to respond to otoprotective drug therapy. The short interval from initial hearing loss to deafness (P27–P90) makes this model ideal for screening and validating otoprotective drugs.
The video contains the various pharmacogenomics appications in the drug industry
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Pharmacogenomics
Department Chair and Full Professor: Biomedical Engineering and Informatics
The Indiana University Luddy School of Informatics, Computing and Engineering at IU Indianapolis invites applications for a tenured full professor position to serve as chair of the Department of Biomedical Engineering and Informatics (BMEI). The appointment will begin January 1, 2025 on the IU Indianapolis campus. Exceptional faculty candidates are being sought to join our expanding and fast-growing department. We welcome applications from established researchers with collaborative research teams. Candidates will be considered from all areas at the intersection of informatics, computing, engineering and medicine, including but not limited to bioinformatics, health and clinical informatics, biomedical engineering, bioelectronics and bioengineering. Candidates must be tenured and demonstrate an excellent scholarly record of externally-funded research, effective and well-reviewed teaching, a forward-looking agenda of research and education, and last but not the least a record of leadership experience in an academic setting.
The new chair will have the opportunity to shape and expand a dynamic department on the premier urban research campus of Indiana University. By strengthening or complementing the faculty research in the department, the ideal candidates will use creative, innovative approaches and technologies to address fundamental scientific challenges in one or more areas of biomedical informatics and engineering with broader societal impact, and have the potential to leverage the strengths of Luddy, including: the Polis Center, the Luddy AI Center, leadership on the campus-level Integrated Nanosystems Development Institute (INDI), the unique location in downtown Indianapolis, and interdisciplinary, collegial and collaborative environment, as well as direct access to the research enterprise of IU School of Medicine, the largest medical school in the country, located on the Indianapolis campus. The incoming chair is also expected to further the research impact of the department by leveraging two newly established campus-wide research institutes at IU Indianapolis: The Institute for Human Health and Wellbeing (H2W) and The Convergent Bioscience and Technology Institute (CBATI). These Indianapolis-based institutes will drive transformative research in the areas of health, medicine, life sciences and biotechnology, while equipping IU to nimbly address emerging disciplines. The BMEI department will play a central role in advancing the academic and research mission of these institutes.
Fostering an inclusive environment makes us stronger. The Luddy School in Indianapolis draws on the strengths of an intellectually and culturally diverse community of students, faculty and staff to enrich the educational experience, broaden participation in computing, and meet the needs of emerging technology. We are committed to actively recruiting and retaining students, faculty and staff from all backgrounds and cultures to join the next generation of innovators. We welcome what every individual brings to our learning environment--socially, geographically, and in thought and experience.
The Ideal Candidate
Qualifications
About the Department of Biomedical Engineering and Informatics The Department of Biomedical Engineering and Informatics is home to a dynamic and interdisciplinary group of 18 full-time faculty members, 20+ part-time instructors and nearly 400 students across its Health Informatics, Bioinformatics, Biomedical Informatics (BMI), and Health Information Management (HIM) programs. The department offers a B.S. in HIM, a B.S. in BMI, an M.S. in Health Informatics, an M.S. in Bioinformatics, two Graduate Certificates, a Ph.D. in Informatics - Health and Biomedical Informatics Track, and a Ph.D. in Informatics - Bioinformatics Track. The faculty in the department conduct groundbreaking, externally funded from federal agencies and local life science industry (e.g., NIH, NSF, PCORI, VA, AHRQ and Eli Lilly and Company) research in the areas of bioinformatics, clinical and health informatics, genomics, bioinformatics, computational biology. biomedical engineering, biomedical systems design and mobile technology. Indiana is home to large healthcare exchanges, including Indiana Health Information Exchange (IHIE) and Michiana Health Info Network [MHIN], as well as multiple healthcare systems within Indiana. BHI enjoys close collaborations with IU School of Medicine and the Regenstrief Institute, a pioneering institution in healthcare information technologies. Other partnerships include the IU Center for Computational Biology and Bioinformatics (CCBB), the Luddy AI Center (LAIC), the IU Center for Bioethics, the VA Center for Health Information and Communication (CHIC), Indiana University Health (one of the largest health care organizations in the Midwest), the Schools of Nursing, Dentistry and the Fairbanks School of Public Health.
About the Luddy School of Informatics, Computing and Engineering IU Indianapolis | The Indiana University Luddy School of Informatics, Computing and Engineering is the first completely new school in the United States devoted exclusively to Informatics and a range of its subdisciplines. With its formative national role in creating the nations largest Informatics Program on the Bloomington and Indianapolis campuses, the school is the broadest and one of the largest information/computing schools in the U.S. At IU Indianapolis, the school also has strong ties with the health and life sciences in the areas of health data exchange, clinical decision support, consumer health informatics, integrated health information systems, and interactive health information technologies. The school provides state-of-the-art facilities including fully equipped classrooms, media and gaming labs, humancomputer interaction research labs, usability and mobile development labs, ample research facilities, and studios for sound design and interactive media production. Access to advanced, high-resolution wall-sized displays and virtual environments are also available within the Informatics and Communications Technology Complex. The Luddy School at IU Indianapolis is also home to the nationally recognized Polis Center. The Polis Center works with community partners to develop innovative place-based policies and practices for healthier and more resilient communities by leveraging data in Geoinformatics, Community Informatics and Community Health Informatics.
For additional information about the Indiana University Luddy School of Informatics, Computing, and Engineering, including degrees, course descriptions, plans of study and faculty research, please see luddy.indianapolis.iu.edu.
About Indiana University Indianapolis https://indianapolis.iu.edu/ The IU Indianapolis campus, with over 24,000 students, is located adjacent to downtown Indianapolis. IU Indianapolis is the health and life science campus of Indiana University, the focal point of health profession education in the State of Indiana. IU Indianapolis offers a full range of academic programs, and is an academic leader in the development and use of information technology. The Luddy School in Indianapolis is on the academic Medical Center Campus, home to the Indiana University School of Medicine, the largest medical school in the US. The school has formed key research partnerships with the IU School of Medicine and the Regenstrief Institute, an internationally recognized medical informatics research center. The school also enjoys collaborations with the Roudebush VA Medical Center, IU Health (one of the largest health care organizations in the Midwest), the IU Schools of Nursing, Public Health, Health and Human Sciences, and School of Science. Luddy School faculty have access to state-of-the art computing resources. IUs Quartz supercomputer, Big Red 200 is among the world's fastest research supercomputers. Owned and operated solely by IU, these high-performance resources are designed to accelerate discovery in a wide variety of fields, including biomedicine, biotechnology, health care, and enable effective analysis of large, complex biomedical data sets (i.e., big data).
About Indianapolis Indianapolis is the nations 15th largest city, the capital of Indiana, home to the Indianapolis Motor Speedway, the NCAA, the Indianapolis Colts and Indiana Pacers, Indiana Repertory Theatre, Indianapolis Symphony, Indianapolis Ballet, Indianapolis Museum of Art, Indianapolis Zoo and one of the countrys most livable big cities.
To learn more about Indianapolis, see any of the following websites:
How to apply:Visit https://indiana.peopleadmin.com/postings/24748 for full application instructions. Review of applications will begin immediately, however, the position will remain open until filled. Questions pertaining to this position may be directed to the Assistant to the Chair, Robyn Hart at robhart(at)iu.edu.
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Department Chair and Full Professor: Biomedical Engineering and Informatics job with Luddy School of Informatics ... - The Chronicle of Higher...
HAW RIVER While studies show that many women who study engineering leave the male-dominated field, Alexandra Alex Simmons, 24, says shes found opportunity and ample room to grow at Andersen Sterilizers, a medical device manufacturer in Haw River.
When I was a little girl, I wanted to be a doctor, said Simmons, who excelled at math and science in school. However, I didnt want to invest the many years required to become a doctor. Engineering appealed to me, and when I learned I could pursue bioengineering, I thought it would make good use of my creativity and love of science.
According to the Harvard Business Review, engineering is the most male-dominated profession in the U.S. In fact, in 2022 only 16% of women self-reported as working in science and engineering as compared to their male counterparts, who were two and half times more likely to work as engineers.
A native of Greenville, S.C., who now lives in Durham, Simmons said her upbringing and love for art and design helped shape her dreams. She said she owes her work ethic to her mom, who worked long hours in Greenville as a stylist to support Simmons and her aspirations.
My mom supported everything I ever wanted to do and helped me get to where I am today, she said. No matter what it is I wanted to do, my mom never showed any doubt in my abilities to get there and did what she could to help me pursue those interests. I think having that kind of support allowed me to excel.
Simmons earned a bachelors in bioengineering at Clemson University.
After graduation, I was looking for a job in the medical device field, she said. I accepted a contract position as a validation engineer with Merck.
But Simmons wasnt sure her work at Merck, a global pharmaceutical company with more than 74,000 employees, was making an indelible mark.
I felt like a number, just one among thousands who could easily be replaced, Simmons said. But at Andersen, I feel like I have value and purpose. My contributions make a difference.
Andersen Sterilizers is a family-owned company employing roughly 130 employees. Simmons works with three other engineers, all of whom are men.
Its fulfilling to work with my colleagues and alongside every department at Andersen, Simmons said. Contributing to the production of safe and efficient sterilizers has been exceptionally rewarding.
Simmons said she feels her ideas are heard, and she hopes that more women would recognize the opportunities and rewards found in STEM occupations.
At Andersen, Simmons dedication has earned her high praise, including from Ryan Russell, director of engineering.
Alex is so smart and has such a good mind for detail; something absolutely required of an engineer in any medical-related industry, Russell said. But I think what I like most of all is her stubborn-like determination. ... We are lucky to have Alex.
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Haw River woman trailblazing in bioengineering | | thetimesnews.com - Burlington Times News
FROM NATURE COMMUNICATIONS | for ARTICLE click here.
May 03, 2024
Zara Patel didnt think she would find herself at Mizzou, but after four years on campus she says attending school here was the best decision shed ever made.
Patel will graduate with a degree in biological engineering, which she chose because of her passion for creating technology that has a positive environmental impact. Outside of the classroom, shes been involved in multiple student organizations with focuses on both academics and college traditions.
After graduation, she will begin her career as a water/wastewater designer at Stantec in Indianapolis.
Read on for a Q&A about her time at Mizzou.
Why did you choose Mizzou?
I was born and raised here in Columbia, Missouri. Both my parents went to Mizzou to get their undergraduate degrees and then stayed once they graduated. I never really thought that I was going to go to Mizzou. I always assumed that I would leave the state for college, but once the pandemic began, it was more difficult to go to a school that was out of state and I decided to go to Mizzou. It was one of the best decisions Ive evermade.
What made you interested in your major?
I originally started at Mizzou as a biological sciences major and then switched to biological engineering with an emphasis in bioenvironmental engineering. I always knew I wanted to major in a STEM field and that I wanted to make a difference. I switched majors because I wanted to have a greater connection with creating technology that has a positive impact on the environment, specifically focusing on biological integrations.
How did you get involved at Mizzou?
I am involved in Alpha Omega Epsilon, an engineering and STEM sorority. I am also involved in the Society of Sales Engineers and Engineers Club. Getting to know all the Engineers Week royalty candidates personally, as I was on the royalty committee for the Engineers Club, allowed for me to fully get immersed in the skits. That was my favorite Mizzou Engineering memory.
Whats next for you after graduation?
I have accepted a position at Stantec as a water/wastewater designer in Indianapolis.
What would you tell someone whos interested in coming to Mizzou?
Mizzou is about community and the environment. Whether you come to the school knowing someone or as a total stranger, you will always make friends. Every university has an environment, but Mizzous environment is differentyou can find any group that you want. The first time you fully emerge yourself in the environment, whether it be in classes, student org meetings or at a game, you will know that you made the right choice.
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"The best decision I ever made:" Patel earns degree in biological engineering - University of Missouri College of Engineering
A new initiative in the College of Engineering will serve as the nexus for bio-based technology at UConn.
The Collaboratory for Biomedical and Bioengineering Innovation fosters a vibrant and unified environment where biomedical and bioengineering researchers work together to invent, develop, and adapt existing biotechnologies to solve new problems in the biological sciences.
There seems to be an artificial divide between researchers who focus on biomedical studies and those working on other biological problems, says Leslie Shor, associate dean for research and graduate education and co-director of Collaboratory for Biomedical and Bioengineering Innovation. This is especially strange for engineers, because we are often leading the technical aspects of the work, and an enabling technology such as a novel sensor or new imaging technology works the same regardless of the biological application.
The Collaboratory, however, aims to help researchers establish new interdisciplinary collaborations outside their existing research networks.
By promulgating emerging technologies across fields, we enhance the value of the emerging technology and simultaneously unlock new areas of inquiry and accelerate new discoveries, Shor explains.
Bio-based technology, or biotechnology innovation refers to the development and advancement of technologies that are based on biological systems or use biological materials. This can include a wide range of innovations such as biomedical devices (prosthetics, medical imaging equipment, drug delivery systems); bio-systems (biofuels production, bioremediation of pollutants, agricultural biotechnology); and bio-computation (bioinformatics for analyzing genetic data, computational modeling of biological systems, or machine learning algorithms for drug discovery).
Members of the Collaboratory are nationally and internationally-renowned faculty.
Thanh Nguyen, associate professor of mechanical engineering and biomedical engineering, works at the interface of biomedicine, materials and nano/micro technology. Hes already collaborating with researchers on campus and UConn Health for vaccine, drug, tissue-engineering and biomaterials research, but expects the Collaboratory for Biomedical and Bioengineering Innovation will help strengthen those relationships and allow him to explore more research opportunities.
UConn is already a collaborative and terrific environment for interdisciplinary research. But this initiative makes biomedical and engineering research from different groups much more visible to all researchers at UConn. Nguyen says. The Collaboratory also could eventually lead to more impactful studies and grant funding.
Like Nguyen, Sabato Santaniello, associate professor of biomedical engineering, is interested in potential collaborations with UConn Health and other medical centers in the region. His work in neuromodulation of the cerebellum is primarily targeted to clinical neuroscienceproviding new ways of probing the diseased brain and improving treatments of patients affected by movement disorders.
My work has potential to translate into new, patentable products down the road, but now, my program can benefit the initiative by intercepting the needs of clinicians, especially neurologists and neurosurgeons, he says.
Santaniello describes the Collaboratory as a unique platform that will regionally advertise the many cutting-edge biomedical technologies that UConn faculty develop and better intercept the needs that come from the healthcare industry and the clinical research.
It will benefit greatly those PIs at UConn who are looking for new, exciting applications for the tools that are developed in their labs, he says.
The group aims to promote bio-based technologies through collaborative research; boost economic growth in Connecticut by creating new bio-based products and businesses; train students for biotech careers by involving them in research and innovation; and establish UConn as a global leader in bio-based technology innovation.
Our goals are to drive research, investment, and possibilities in Connecticut, explains Guoan Zheng, associate professor of biomedical engineering and co-director of the Collaboratory for Biomedical and Bioengineering Innovation. By advancing technology, we believe we can make a significant impact on scientific discovery and its applications driving socially impactful research and benefiting Connecticuts economy and workforce.
Shor, whos also Centennial Professor of Chemical and Biomolecular Engineering, leads the Engineered Microhabitats Research Group at UConn, where she mentors an interdisciplinary team focusing on biotechnology for sustainability. My lab simply adapted established microfluidics or lab-on-a-chip technologies to a completely different field of biology: soil microbes living near plant roots. This approach directly led to new understanding about soil moisture regulation by bacteria and fungi and a new appreciation for how soil protists can be used to promote more sustainable food production. I want to see the same interchange of approaches advance all types of biological sciences to advance a healthy and sustainable future, she said.
The Collaboratory is seeking student, faculty, and corporate partners. For more information, contact the UConn Collaboratory.
The Collaboratory for Biomedical and Bioengineering Innovation celebrated its launch April 2 with a networking symposium and poster session. Faculty from several engineering disciplines attended to learn about the interdisciplinary relationships related to biomedical and bioengineering research and technology innovation. Photos of the event are below and in this UConn College of Engineering Flickr album. (Chris LaRosa/UConn)
Bioengineering student Daniela Meson De La Fuente is pictured with the research poster she presented at the 2024 Maize Genetics Meeting.
Oakland University student Daniela Meson De La Fuente recently presented research at the 2024 Maize Genetics Meeting, an international conference that brought together researchers whose work advances the field of maize (corn) genetics and breeding.
The sophomore bioengineering major attended the meeting in Raleigh, North Carolina after receiving a MaGNET Award, a competitive travel grant aimed at members of underrepresented groups.
I was extremely excited when I received the news, as only five undergraduates received the awardfrom hundreds of attendees, she said. This award was funded by the National Science Foundation to create diversity in our future researchers.
As a member of Dr. Shailesh Lals research laboratory, Meson De La Fuente is researching a gene that exists in corn and humans, serving important functions for both.
Our laboratorys prior work led to the discovery of a novel RBM48 gene in maize, which was later found to be homologous in humans, she said. A mutated RBM48 gene can lead to developmental defects in both maize and humans. It is likely that this gene is associated with developing diseases, including cancer.
While working in the lab, Meson De La Fuente has been mentored by Dr. Lal and graduate student Dalton Raymond.
Dalton has been my mentor since the summer of 2023, when I was accepted to be part of the Summer Undergraduate Research Program (SURP), she said. He had been working on this research project since I joined the lab team, and I helped him continue the project.
She also credited Dr. Lal for encouraging her to apply to SURP, as well as for the MaGNET Award.
Heexemplifies a professor who goes above and beyond to ensure his students have everything they need toachieve their goals, she shared. I like that Oakland University has countless opportunities for undergraduate students to explore theirinterests by getting involved in research, something that is very rare and unique to be available for an early-career student.
To receive a MaGNET Award, Meson De La Fuente submitted a detailed application, including information about her research, academic performance, career aspirations and a recommendation letter from Dr. Lal.
"Daniela is a dedicated studentwho excels inacademic and extracurricular activities, said Lal, professor and chair of OUs Department of Bioengineering.
He lauded her strong leadership qualities, including her roles as an OU Student Congress legislator,treasurer of the OU Engineering in Medicine and Biology Society, member of the OU Chapter of Sigma Xi Scientific Society, andmember of the Society for Advancement of Chicanos/Hispanics and Native Americans in Science.
She has a bright career ahead of her in whatever she decides to pursue, Lal added.
At the conference, Meson De La Fuente presented her work on developing a method to discover the cause of the RBM48 gene mutations associated with human disease. The data generated from the study could help pave the way for development of treatments for certain cancers.
Along with sharing her research, she also learned from other student researchers and gained insight into how companies are leveraging the latest advances in agricultural science.
I hadan amazing experience at the meeting. I not only got an inside view of how other student presenters came about pursuing a master's or Ph.D., which was very helpful, but I also had the opportunity to connect and network with businesses such as Syngenta and Corteva, Inc. and learn about their innovative agricultural projects, she said. I met people from universitiesworldwide,which broadened my perspective on collaboration opportunities in research.
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Student receives MaGNET Award to present research at international genetics conference - News at OU
David Walt, Ph.D., winner of the 2023 Fritz J. and Dolores H. Russ Prize, discussed his transformative research work and its impact on human health in a special presentation at Ohio University.
Awarded biennially by Ohio University and National Academy of Engineering (NAE), the Fritz J. and Dolores H. Russ Prize recognizes outstanding bioengineering achievements in widespread use that improve the human condition.
Dr. Walt received the 2023 Russ Prize for the development of microwell arrays that have greatly advanced the fields of genomics and proteomics, said Russ College of Engineering and Technology Dean Patrick Fox while introducing Walt.
The Russ Prize is the top bioengineering award given worldwide, Fox said.
Walt spoke to students, faculty, staff and area residents in the Baker University Center Theater on March 28, about Discovery, Scale and Impact. His lecture focused on how ideas happen in the laboratory and then get translated into the commercial sector.
And then, eventually, we hope, they make an impact on human health, Walt said.
In his presentation, Walt discussed the founding of the companies Illumina and Quanterix.
In the 1990s, Walt explained, he was working in the field of optical sensors and imaging optical fibers, when one of the individuals in his laboratory found a way to create microwells.
This was a mistake, this was the opposite of what he was trying to do, Walt explained.
We did not pay attention at first, he said. A graduate student in his laboratory later found a way to put beads of liquid in the microwells, but there was no use for this at the time.
The next year, though, Walt was involved with research involving DNA sequence testing and realized that the microwells could be very beneficial in his research work and the work of others.
At that instant, I just had an epiphany, Walt said.
That original accidental discovery and the realization of what could be done with the microwell arrays led to the founding of Illumina, which then led to new collaborations that changed Walts life and transformed the field of genetics. He explained the work that Illumina was able to do with the technology and how it greatly expanded research possibilities.
Walts research work included identifying which genes are responsible for different diseases.
An important part of understanding the role of various genes in disease is to identify single nucleotide polymorphisms (SNPs; pronounced snips). At the time he was doing this research work with Illumina, in order to get one SNP, it would cost $2 per SNP, Walt said. In order to do the proper research work, though, it would take 1,000 gene SNPs from 1,000 subjects, which made the project far too expensive to be feasible.
Illumina, though, was able to introduce the product, the Array Matrix, which was able to do gene SNPs quickly and at a low price. That technology revolutionized this research work and drove the evolution of more new products.
That technology also led to the development of the company 23 and Me.
Its also the technology that was used for ancestry.com, Walt said.
These technological advances turned Illumina into a company that today is worth $30 billion.
Really, thats not where the impact starts, Walt said. He is proud of its financial success, but whats much more important is how the company has impacted human health.
This can be seen in the clinical applications, he explained. In one example, he discussed how scientists were able to help a family with a genetic disease, and how this can be applied further.
In another example, he explained how researchers found a new way to identify cancer.
Now this is not just an economic impact, its really a human health impact, Walt said.
Walt also discussed new technologies that led to the founding of the start-up company, Quanterix. This company has great potential to also make a difference in human health as it is doing research work into areas such as prostate cancer, breast cancer and COVID-19.
While talking about his research work, Walt stressed that he is grateful for all of the assistance he has received from everyone who has worked in his laboratories over the years. He said he is also thankful for the support of his funders and benefactors.
Walt also thanked the Russ Family and said he was honored to receive the Russ Prize.
Thank you for the opportunity to present the Russ Lecture here, Walt said, adding that he had enjoyed his time at Ohio University.
To watch a recording of Walts lecture, please see this website.
To read more about Walt and his research work, please see this OHIO News article.
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Russ Prize winner David Walt discusses his groundbreaking research - Ohio University
Sherry (Xue) Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering (CBE)in the School of Engineering and Applied Science, always knew she had a future in the lab. I grew up in China, and when I was little, maybe 6 or 7, she recalls, my teacher asked me, What do you want to be when you grow up? I said, I want to be a scientist.
Neither of her parents had studied beyond high school; when Gao finished her training as a chemical engineer, she became the first person in her family to graduate from college. One of my greatest motivations is to help first-generation college students, Gao says.
Now, as the newest faculty member in CBE, Gao is prepared to do just that: support the next generation of chemical engineers, while also conducting groundbreaking research in the development of small molecules to edit genes, pushing the boundaries of precision medicine.
One of Gaos primary goals is to make gene-editing tools more accurate. As Gao points out, CRISPR, the revolutionary technology developed by Nobel Prize winners Jennifer Doudna and Emmanuelle Charpentier, doesnt always work perfectly. The tool goes in, fixes a mutation, but we also observe a lot of off-targets, Gao says. So its not just hitting the target letters in our genetic code, its sometimes editing other places. You could cure one genetic disease by using the CRISPR tools, but then the off-targets could cause dozens of other problems.
More generally, Gao is fascinated by enzymes, the class of molecules to which CRISPR belongs, which enable chemical reactions by lowering the activation energy required for a reaction to take place. Enzymes typically catalyze molecules in a very precise fashion, says Gao. Thats sort of my passion: to look into how nature makes some molecules so accurate, and how we as humans and engineers can learn from that.
This story is by Ian Scheffler. Read more at Penn Engineering Today.
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Sherry Gao pushes the boundaries of genetic engineering | Penn Today - Penn Today
Karin Wuertz-Kozak, a faculty researcher at Rochester Institute of Technology, was recently inducted into the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows. Becoming an AIMBE Fellow, one of the organization's most prestigious honors, signifies inclusion among the top 2 percent of medical and biological engineers, representing the most accomplished individuals across academia, industry, education, clinical practice, and government.
Wuertz-Kozak, a Kate Gleason Endowed Professor in RITs Department of Biomedical Engineering, was recognized for her outstanding contribution to understanding the pathophysiology of degenerative disc disease and to developing new therapeutic strategies for disc disease. She brings an interdisciplinary background to her work with experience in pharmacology, biomedical engineering, and biology, as well as business administration. Her clinical collaborations are worldwide, spanning locally with the University of Rochester to the Fukushima Medical University in Japan.
Karin is conducting important research that will ultimately improve the quality of life for individuals suffering from degenerative disc disease, said Doreen Edwards, dean of RITs Kate Gleason College of Engineering.We are thrilled that she is being honored with this prestigious award.
Wuertz-Kozak is leading research on the role and effects of mechanical loading in the context of back pain. Understanding the mechanisms leading to degeneration and chronic inflammation can give clues to relieving disc-related back pain and is a crucial part of developing novel, molecular treatment options for patients, she said.
One promising approach being developed by her research team is to modulate and control tissue inflammation and induce regeneration is through extracellular vesicles (EVs) derived from CRISPR-modified stem cells. While stem cells have proven successful in the regeneration of many tissues, the intervertebral disc constitutes a drastically harsh cell environment, making EV therapy a promising alternative to cell therapy. To this end, she has received several significant research grants from prominent agencies such as the National Science Foundation and the National Institutes of Health.
A longtime member of several national and international associations, Wuertz-Kozak has held leadership positions with the International Society of the Study of the Lumbar Spine and the Orthopedic Research Society. Among her many academic achievements, Wuertz-Kozak has been recognized by the Swiss National Science Foundation Professorship Award in 2016 and received a Faculty Scholarship Award as part of RITs Kate Gleason College of Engineering in 2021. She has published more than 90 peer-reviewed articles and has contributed to numerous journals related to molecular science and biomedical engineering in editorial roles and as a reviewer.
AIMBE Fellows are employed in academia, industry, clinical practice, and government., and consist of distinguished medical and biological engineers including three Nobel Prize laureates and 22 Presidential Medal of Science and/or Technology and Innovation awardees. Each has led initiatives to pioneer new and developing fields of technology, making major advancements in traditional fields of medical and biological engineering, or developing/implementing innovative approaches to bioengineering education.
image:
Shay Soker, PhD
Credit: Wake Forest Institute for Regenerative Medicine
Winston-Salem, North Carolina April 2, 2024 Dr. Shay Soker, a distinguished professor at the Wake Forest Institute for Regenerative Medicine (WFIRM), has been honored with induction into the 2024 Class of College of Fellows for the American Institute for Medical and Biological Engineering (AIMBE). This recognition highlights Dr. Soker's contributions to the field of regenerative medicine and his dedication to advancing biomedical engineering.
Dr. Soker's extensive research portfolio spans various critical areas within regenerative medicine, including the identification of novel cell sources, the development of innovative scaffolds for tissue engineering, tissue neovascularization, real-time imaging technologies, and the fabrication of bioengineered tissues for both developmental and disease modeling.
Induction into the AIMBE College of Fellows stands as a top achievement for medical and biological engineers, reserved for the top two percent in these fields, recognizing individuals who have made exceptional contributions to research, practice, or education in engineering and medicine. The AIMBE acknowledges the pioneering work of researchers advancing new technologies and methodologies, whether through traditional fields or through innovative approaches to bioengineering education.
Dr. Sokers pioneering work has significantly advanced our understanding of tissue regeneration and has led to transformative breakthroughs in the field. Notably, Dr. Soker's research has led to the use of vascularized scaffolds for whole organ bioengineering, offering promising prospects for the development of viable organ replacements and regenerative therapies, stated Dr. Anthony Atala, Director of WFIRM.
Commenting on his induction into the AIMBE College of Fellows, Dr. Soker expressed profound gratitude and emphasized the collaborative efforts of his team and colleagues. He stated, "It is a tremendous honor to be recognized by the AIMBE, and I am deeply grateful for the support of my colleagues and collaborators who have contributed to our shared pursuit of advancing regenerative medicine."
Fellows with AIMBE include members from over 30 countries employed in industry, healthcare, academia and government.
Dr. Shay Soker received his PhD from the Technion-Israel Institute for Technology, followed by a postdoctoral fellowship at the Childrens Hospital Boston and Harvard Medical School. He was then recruited to the Laboratory for Tissue Engineering and Cellular Therapies and promoted to Assistant Professor of Surgery at the Harvard Medical School. Currently, Dr. Soker is a Professor of Regenerative Medicine and the Chief Science Program Officer at the Wake Forest Institute for Regenerative Medicine.
About the American Institute for Medical and Biological Engineering (AIMBE): AIMBE is the authoritative voice and advocate for the value of medical and biological engineering to society. AIMBEs mission is to recognize excellence, advance public understanding, and accelerate medical and biological innovation. No other organization brings together academic, industry, government, and scientific societies to form a highly influential community advancing medical and biological engineering. AIMBEs mission drives advocacy initiatives into action on Capitol Hill and beyond. For more information, visit http://www.aimbe.org.
Media contact: Charlie Kim, ckim@aimbe.org
About Wake Forest Institute for Regenerative Medicine: The Wake Forest Institute for Regenerative Medicine is recognized as an international leader in translating scientific discovery into clinical therapies, with many world firsts, including the development and implantation of the first engineered organ in a patient. Over 500 people at the institute, the largest in the world, work on more than 40 different tissues and organs. A number of the basic principles of tissue engineering and regenerative medicine were first developed at the institute. WFIRM researchers have successfully engineered replacement tissues and organs in all four categories flat structures, tubular tissues, hollow organs and solid organs and 16 different applications of cell/tissue therapy technologies, such as skin, urethras, cartilage, bladders, muscle, kidney, and vaginal organs, have been successfully used in human patients. The institute, which is part of Wake Forest University School of Medicine, is located in the Innovation Quarter in downtown Winston-Salem, NC, and is driven by the urgent needs of patients. The institute is making a global difference in regenerative medicine through collaborations with over 500 entities and institutions worldwide, through its government, academic and industry partnerships, its start-up entities, and through major initiatives in breakthrough technologies, such as tissue engineering, cell therapies, diagnostics, drug discovery, biomanufacturing, nanotechnology, gene editing and 3D printing.
Media contact: Emily Gregg, egregg@wakehealth.edu
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.
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Shay Soker, PhD, inducted into the College of Fellows for the American Institute for Medical and Biological Engineering - EurekAlert
Mayo Clinic is taking steps to bolster the medical marvel of transplantation while addressing the confounding problem of a critical shortage of donor organs. It created the Transforming Transplant Initiative with a bold goal of providing organ transplants for everyone who needs one. Another objective is to eliminate the waitlist that has grown to more than 100,000 people in the U.S.
"My vision is to not just help one patient, but help the thousands who have end-stage organ failure get lifesaving transplants," says C. Burcin Taner, M.D., a Mayo Clinic surgeon who leads the initiative. Dr. Taner is also the chair of the Department of Transplantation at Mayo Clinic in Florida.
The Transforming Transplant Initiative was created as a collaboration between the Department of Transplantation and Mayo Clinic's Center for Regenerative Biotherapeutics. The project seeks to overcome the shortcomings of transplantation, the greatest of which is the need for more organs. Researchers working to improve transplantation ask tough questions like, "Could we bioengineer organs to reduce or eliminate the wait list?" To answer that question, Mayo Clinic has formed a collaboration with Carnegie Mellon University, pairing medical expertise with engineering know-how to make experimental organs.
"Bioengineering new organs is promising, but complex. We're looking at a research timeline of 10-15 years to potentially bring this new option to patients," says Dr. Taner.
This bioengineering research brings together 3D bioprinting, tissue engineering, biomaterials and cellular materials to grow humanlike organs.
The research is focusing on nine different bioengineering projects ranging from better ways of monitoring the health of transplanted organs to engineering complex organs such as hearts, lungs, livers and kidneys.
The Center for Regenerative Biotherapeutics is supporting the project with biomanufacturing, stem cell technology and other resources.
"Regenerative biotherapeutics seeks to repair or replace diseased organs. As such, we are very excited to be part of the Initiative for improving transplantation," says Wenchun Qu, M.D., Ph.D., the Jorge and Leslie Bacardi Associate Director, Center for Regenerative Biotherapeutics in Florida. "We hope to assist in the build out of this project by providing researchers, workspace, biomanufacturing capabilities and cell and gene technologies."
Another challenge the Transforming Transplant Initiative is trying to address is graft failure or rejection of transplanted organs. Mayo Clinic's vision is to prevent the need for a second transplant. One research project is focusing on whether chimeric antigen receptor-T cell therapy (CAR-T cell therapy) could be used to control the body's immune response and prevent organ rejection. CAR-T therapy has mainly been used to treat blood cancers. Applying this technology to transplants would be a new, experimental use of CAR-T therapy.
"Some organ transplant patients have antibodies in their bloodstreams that increase their chances of (organ) rejection. Unfortunately, that makes it difficult to find a proper match," says Dr. Taner. "We hope research will show whether CAR-T cell therapy could harness the immune system to suppress antibodies that are causing rejection." Other Mayo Clinic goals include reducing the number of organs that are discarded and making more organs available through advanced preservation techniques. Another goal is to identify and treat disease early to prevent end-stage organ failure and the subsequent need for a transplant.
Mayo Clinic leaders recognize that overcoming the complex barriers to organ transplantation will require powerful new collaborations. They are actively seeking new ways to work with experts in industry and academia that could bring new ideas, tools, specialized knowledge and energy to the field.
"Organ transplantation is one of the greatest accomplishments in modern medicine. There is also a lot of good expertise outside our organization," says Dr. Taner. "We welcome outside collaborators that could help us improve organ transplantation for patients."
It could take many years to realize the fruits of the Transforming Transplant Initiative. Nevertheless, Mayo Clinic researchers continue to work tirelessly to address the critical shortage of organs and bring the gift of organ donation to more people.
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Related stories: Four ways organ transplants are being transformed to save lives Transplant program at Mayo Clinic in Florida celebrates its 25th anniversary with vision for future of transplant
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Transforming Transplant Initiative aspires to save lives through bioengineering - Mayo Clinic
Photo caption: The Schwartz lab discovered that molecules move around on surfaces via a complex type of motion involving crawling, hoppingand flying.
Professor Dan Schwartz
Professor Daniel K. Schwartz has been honored with the prestigious American Chemical Society (ACS) Division of Colloid and Surface Chemistry 2024 Langmuir Lectureship award. He was nominated by his colleagues for significant contributions to the field of colloid and interface science.
Colloids are mixtures in which one substance is finely dispersed in another substance. Interface science refers to the boundaries between different phases of matter, such as between two unmixable liquids, or between a liquid and a solid.
Schwartz, a professor in CU Boulders Department of Chemical and Biological Engineering, said the award was significant for several reasons.
Most importantly, it recognizes the excellence of research performed by my PhD students and postdocs, past and present, he said. The recognition is also special because it is sponsored jointly by the ACS Division of Colloid and Surface Chemistry and the ACS journal Langmuir, both of which are very close to my heart. The namesake of the award, Irving Langmuir, a Nobel laureate and the foundational figure of surface science, is a long-time scientific hero of mine.
Schwartz will receive a commemorative plaque, complimentary registration and reimbursement for travel expenses to the ACS fall 2024 meeting and a $3,000 award. He will also deliver a special lecture at the ACS fall 2024 symposium.
Schwartzs colloid and interface science research carries significant practical implications for various fields. These include membrane-separation processes and biocatalysis applications such as water purification, wastewater treatment, food and beverage processing and pharmaceutical manufacturing. His work also extends to chemical production as well as environmental remediation and biofuel synthesis.
Dans contributions to fundamental understanding of dynamic interfacial phenomena are extraordinary, the nominators said in a letter to the selection committee. He has provided new windows into monolayers at interfaces, on solid boundaries and new approaches to understanding fundamental transport of confined molecules, nanoparticles and active particles in porous media. This work is of extraordinary scope and rigor.
The award also entails an expectation that Schwartz will submit a feature article for publication in Langmuir within six months following his lectureship presentation.
It is incredibly satisfying to share the award with my PhDs and postdocs, Schwartz said. Im eagerly looking forward to the opportunity to describe their work to the award lecture audience in August.
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Research of extraordinary scope and rigorDan Schwartz honored by American Chemical Society - University of Colorado Boulder
Animal use
Yorkshire pigs (3040kg; age approximately 12weeks old) were used for all decellularization and recellularization experiments. All studies were approved by the Institutional Animal Care and Use Committee (IACUC) of the University Health Network and Toronto General Hospital Research Institute. Humane care was provided to all animals in accordance to the Principles of Laboratory Animal Care defined by the National Society for Medical Research and the Guide for the Care of Laboratory Animals issued by the National Institutes of Health. Reporting of use of experimental animals in this study followed recommendations specified by the ARRIVE guidelines.
Pigs were fasted for 12h prior to surgery. Sedation was achieved with ketamine (20mg/kg IM), atropine (0.04mg/kg IM) and midazolam (0.3mg/kg IM). Anesthesia was induced by inhalation of 5% isoflurane through a mask at a flow rate of 22 to 44mL/kg/min to facilitate peripheral line insertion and intubation. Anesthesia was maintained with isoflurane (0.5 to 2%). Pigs were intubated with an appropriate endotracheal tube (78mm) and ventilated to a tidal volume of 8mL/kg, positive end-expiratory pressure of 5cm H2O, FiO2 of 0.5 and respiratory rate of 14 breaths per minute. Pigs were prepped and draped in the usual sterile fashion prior to flap procurement. Surgical procedure for porcine omentum and TFL flaps procurement were as previously described30. Briefly, the omental flap was procured by midline laparotomy and the left gastroepiploic artery and vein was used as the dominant vascular conduit. The right gastroepiploic vessels were ligated to prevent perfusion flow-through.
The TFL flap was procured with pigs in the lateral decubitus position. The main vascular pedicle was defined by the ascending branch of the lateral circumflex femoral artery and veins. The overlying skin island was removed to produce a pure fascial flap. Following flap detachment, the vascular pedicle was cannulated with 2022 G Angiocath (Becton Dickenson) under direct vision and flushed with 20 U/mL heparin sodium (LEO Pharma, Denmark) in 0.9% normal saline and transported under sterile conditions to the lab.
Porcine flaps were perfusion-decellularized using low-concentration SDS followed by DNase (Sigma Aldrich) reconstituted to a concentration of 10mg/mL, as previously described30. Cannulated flaps were each connected to a perfusion system to allow antegrade perfusion via the arterial inlet at 2ml/min, in which solutions: 0.05% SDS followed by 0.1mg/mL deoxyribonuclease (DNase) were perfused through the flap vasculature with 1phosphate buffered saline (PBS) perfusion in between to remove residual detergent. Flaps were sterilized in 0.1% paracetic acid (PAA) / 4% ethanol (EtOH) (Sigma Aldrich) and then washed in 1PBS prior to recellularization. As described previously30, omental and TFL flaps were perfused with SDS for 2 and 3days, respectively. Following SDS perfusion, flaps were washed with PBS for 24h and then perfused with DNase for 2h, PBS for again for 24h, and finally PAA/EtOH for 3h. With the exception of DNase, each step included an exchange of the submersion fluid to match the given perfusate. For the DNase step, flaps were submerged in fresh PBS.
Commercially available HUVECs (American Type Culture Collection/ATCC, USA) were cultured in EGM-2 (Lonza, Switzerland) supplemented with SingleQuots (Lonza) of Growth Supplements including: FBS 2%, hEGF, hydrocortisone, Gentamicin/Amphotericin-B, VEGF, hFGF-B, R3-IGF-1, ascorbic acid, and heparin (concentrations proprietary). Commercially obtained human bone-marrow derived MSCs (Promocell, Germany) were cultured in MSCGM (Promocell) containing proprietary media supplement and 5% FBS. HMSCs and HUVECs between passage 4 and 6 were used for recellularization. Both cell types were verified for correct functional and phenotype expression. HUVECs expressed CD31/VE-Cadherin using flow cytometry and were functionally capable to undergo angiogenesis. MSCs were CD90/73/44 positive and CD34/45/11b negative using flow cytometry and capable of undergoing trilineage differentiation (Supplementary Fig.1). These findings were consistent with the minimal criteria to define MSCs according to the International Society for Cellular Therapy Criteria47.
All cells were maintained in 150 cm2 dishes until reaching 90% confluency (resulting in approximately 50,000 cells/cm2). Cells were detached from culture vessels with 0.25% trypsinEDTA solution (Gibco) prior to recellularization. Cell media was replaced every other day, and the cultures were maintained in a humidified 95% air/5% CO2 incubator at 37C.
A closed-system bioreactor was set up in an incubator for recellularization within the flap scaffold matrix. We used a modified airtight snap-lid container, previously used for decellularization with a closed-circuit L/S-16 (Masterflex, Fisher Scientific) silicone tubing. The end of the tubing external to the tissue chamber was fitted with a female Luer thread-style panel (Cole-Parmer), which connected to a 3-stop tubing compatible with peristaltic pump (Ismatec, Cole-Parmer) tubing cassette as previously used for perfusion-decellularization. The opposite end of tubing was reconnected to the second port from the tissue chamber to allow closed-loop circulation of medium from tissue chamber into the flap via the arterial cannula at a flow rate of 2mL/min. Just proximal to the tissue chamber, silicone tubing was connected to a three-way stopcock (Baxter, USA). The chamber was filled with 200mL of EGM-2 media, which was primed through the tubing to remove air bubbles. Decellularized flaps were perfused with EGM-2 at 2mL/min in conventional cell culture incubator at standard conditions (95% air/5% CO2) overnight before cell seeding to equilibrate flaps with culture medium.
Cell seeding was performed as follows: HUVECs and human bone-marrow derived MSCs were lifted from tissue culture plastic with 0.25% trypsin and centrifuged at 500g for 5min. The resultant cell pellet was resuspended in 10mL media, strained with 75m pore mesh, and counted via automated hemocytometer (Vi-Cell XR, Beckman Coulter). A total of 8107 cells, divided equally with 4107 HUVEC co-cultured with 4107 MSCs, were used for recellularization of each scaffold. A combined cell suspension of the two cells were slowly manually injected into the vascular arterial inlet through a three-way stopcock. Following the introduction of cells, flaps were placed in a standard cell culture incubator for 2h of static culture to allow cell attachment. Afterwards, perfusion-culture was initiated with the peristaltic pump (Ismatec, Cole-Parmer) running at 2mL/min for 6days. Media passed through the flap was recovered back into the reservoir using a separate pump channel that drained the bioreactor at an equal rate to the perfusion, allowing for recycling and reuse. Media was exchanged every other day for fresh EGM-2. A total of 750mL of culture medium was used over 6days for each flap.
Native, decellularized, and recellularized tissues were biopsied near the distal margin of the flap, fixed in 10% formalin (Fisher Scientific), embedded in paraffin, and sliced into 5m sections on microtome (Leica Biosystems). Slides of the paraffin-embedded samples were processed for histological and IHC staining. Histologic staining was performed on xylene-deparaffinized slides with the following stains: H&E (Sigma Aldrich), Massons Trichrome (American MasterTech Scientific), and Verhoeff Van Gieson Elastin Stain (Abcam).
For IHC, heat induced antigen retrieval was done with citrate buffer (pH 6.0; Thermo Fisher Scientific) in a 95C autoclave for 10min. Endogenous peroxidases were blocked with a peroxide block (Cardinal Health), and nonspecific binding was blocked with Dako Serum-Free Protein-Block (Agilent). Sections were incubated with the primary antibodies at 4C overnight with dilutions as follows: rabbit polyclonal anti-Collagen IV (Abcam, ab6586, 1:300), rabbit polyclonal anti-Fibronectin (Abcam, ab23751; 1:400); and rabbit polyclonal anti-Laminin (Abcam, ab11575, 1:400) and anti-CD31 (Abcam, ab28364, 1:50) at 4C overnight. Slides were washed three times in PBS with 0.1% Tween and goat anti rabbit IgG HRP-conjugated secondary antibody (ImmPRESS Peroxidase Polymer Reagent, Vector Laboratories) was applied for 30min. Slides were again washed thrice in PBS-Tween and then diaminobenzidine solution (Vector Laboratories) applied for 10min. Slides were counterstained with hematoxylin. After staining, all slides were dehydrated in ethanol to xylene exchange, mounted and imaged on Aperio CS2 Slide Scanner (Leica Biosystems).
Immunofluorescence staining was performed using paraffin embedded sections cut to 5m thickness and deparaffinized using xylene and rehydrated in serial dilutions of ethanol. Tissue sections in were incubated in antigen retrieval buffer (10mM citrate buffer, pH 6.0) at 95C for 10min in an autoclave. Tissue sections were then blocked with 5% blocking serum (goat serum) in 1% bovine serum albumin (BSA) before adding primary antibody. Slides were then incubated with primary antibodies for VE-Cadherin (Abcam, ab33168, 1:100) and vimentin (Abcam, ab92547, dilution 1:200) diluted in 1% BSA at 4C overnight. After washing three times with PBS-Tween, slides were then incubated for 1h at RT in the secondary antibody goat anti-rabbit IgG conjugated with AlexaFluor 647 (Thermo Fisher Scientific, 1:500). Finally, slides were washed three times with PBS-Tween in the dark and counterstained with DAPI (Abcam; 1:5000). Negative controls were used by replacing the primary antibody with the corresponding isotype (IgG) of the primary antibody. Images were taken on a Leica SP8 confocal microscope with LAS X software (Leica Biosystems) installed.
Tissue pieces (~3040mg) were obtained by punch biopsy tool and dried in 60C oven overnight. Dried tissue pieces were digested in papain solution at 65C for 18h. Corresponding native flap tissues were dried and digested in parallel as controls. Papain (Sigma Aldrich, 16 units/mg protein) 1530mg/mL stock was solubilized to working concentration of 0.1mg/ml in 0.1M phosphate buffer (pH 6.0), with 5mM cysteine hydrochloride (Sigma Aldrich), and 5mM EDTA (Sigma Aldrich). The lysates were used for detection of sulfated glycosaminoglycan (sGAG) and DNA content. The Blyscan Sulfated GAG Assay kit (Biocolor) was used to measure sGAG according to manufacturers instruction. Briefly, tissue specimen lysates were mixed with Blyscan Dye Reagent to bind the GAG for 1h at room temperature. The GAG-dye complex was then collected by centrifugation at 10,000g. After the supernatant was removed and the tube drained, Dissociation Reagent was added and 100l of analyte solution was transferred to a 96-well plate. Absorbance against the background control was obtained at a wavelength of 656nm with a SpectraMax spectrophotometer (Molecular Devices). GAG amount was interpolated from a standard curve (05g) using a known GAG standard provided in the kit. Final GAG content was standardized to the total dry tissue mass (mg) used for assay.
For DNA content quantitation, the tissue lysate following papain digestion (above) was used. The Quant-iT PicoGreen dsDNA Assay Kit (Invitrogen) was used to measure DNA content according to manufacturers instruction. Fluorescence reading (excitation: 485nm and emission: 528nm) was taken on a plate reader (Cytation 5, Biotek), and the absolute amount of DNA (ng) was quantified against a lambda DNA standard curve (01000ng) provided by the manufacturer; final DNA content was standardized to total dry tissue mass (mg) used for assay.
All statistical analysis was performed using GraphPad Prism, version 9.0 (GraphPad, Inc.). Statistical analyses was conducted with multiple unpaired t test with a significance level of p<0.05. Values are presented as mean, with S.D. unless stated otherwise.
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Bioengineering of vascularized porcine flaps using perfusion-recellularization | Scientific Reports - Nature.com
In living cells, molecules can come together through a dynamic, transient process, forming droplets that hold the components needed for a specific job.
Once they come together, these molecular assemblies can break down nutrients, send signals to neighboring cells, or turn on stress responses.
Jerelle Joseph seeks to uncover the rules behind the formation and evolution of these droplets, known as biomolecular condensates.
These membraneless structures are liquid-like. They exhibit characteristics like flowing, dripping, and fusing, and form by phase] separation like oil droplets in water, said Joseph, who joined Princeton in January 2023 as an assistant professor of chemical and biological engineering.
What makes them very exciting, both to study and potentially to engineer, said Joseph, is that they have vast functions and implications for health and disease.
Josephs team uses computer simulations to examine the formation of biomolecular condensates droplets that contain hundreds of protein molecules, and sometimes DNA or RNA, and play roles in regulating growth, metabolism, and more.
Researchers understanding of biomolecular condensates has come a long way since Princeton professor Clifford Brangwynne and others first described the emergence of these cellular compartments nearly 15 years ago. Still, many questions remain about the conditions that drive condensates to form, and how they change over time.
If we can understand how condensates form and are regulated, we can engineer them, said Joseph. Essentially, we want to reverse-engineer condensates to find out how they come about. And also, forward-engineer them to create new functionalities within cells or to prevent unwanted functions, such as cancer or neurodegenerative diseases. Joseph is also excited by the possibility of engineering plant metabolism for sustainable food production.
But before these applications can come to fruition, Joseph and her team must develop computational models that are accurate enough to faithfully represent organization within living cells, yet efficient enough to run on todays computers.
A growing body of experimental data on how condensates form and change is crucial to grounding her teams models, said Joseph. Her postdoctoral work at the University of Cambridge included developing simulations to predict the phase separation of proteins, achieving a new degree of accuracy.
Now, we want to be able to describe a wider breadth of proteins as well as nucleic acids that undergo phase separation such as RNA. So, we need to be able to augment and enhance our approaches to better describe more complex systems, she said.
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Simulations reveal workings of droplets that underlie life's functions- Princeton Engineering - Engineering at Princeton University
The snapshot
3DBioFibR Inc. formed three and a half years ago, spun out of research conducted in Dalhousies School of Biomedical Engineering with support from Dal Innovates. The companys technology, a bold new approach to tissue engineering, is making it a go-to in the burgeoning medical research sector.
3DBioFibRs technology has its roots in the work of Dr. John Frampton, Dalhousies Canada Research Chair in Cellular, Biomaterial and Matrix Interaction. Dr. Frampton invented a technique for manufacturing protein fibres used as scaffolding to build cellular structures. Like the rebar in a concrete building, the fibers provide an underlying framework that cells latch onto to artificially manufacture structures for use in the human body.
His initial protein fibers were encouraging but they didnt contain enough collagen to be clinically successful. Collagen is the most abundant protein in the human body. Dr. Frampton knew that incorporating it in his fibers would allow him to vastly improve how cells bond to them.
Collagen fiber being made. (Photo provided)
He recruited fellow Dal researcher Dr. Laurent Kreplak and graduate student Gurkaran Chowdhry to pursue the idea. Together the team built on Dr. Framptons fiber creation technique to finetune it and were incredibly successful upping the collagen content from two per cent to 100. Moreover, they developed the first fully automated manufacturing system to produce collagen fibers, laying the groundwork for translation to a commercial system.
The innovation meant their new material could become extremely useful in supporting the creation of biomedical structures such as nerves and the c-shaped pieces of cartilage that cushion joints, among many other potential applications.
A close-up look at a scaffold of collagen fibers. (Provided photo)
The goal is for it to act like a structural support for living things to attach to and grow on, Chowdhry explains. It was something that had potential. The next challenge became, can we do it at scale to actually service an industry?
In other words, how would they turn this novel medical technology into a company?
For Chowdhry, that broad question was answered in part with the help of two Dal Innovates programs, now known as Lab2Market Discover and Lab2Market Launch.
My undergrad was in physics, my master's was in physics, so business strategy is not something I had a lot of exposure to. The last business course I took was Grade 11 accounting. So, it was nice to wrap my head around those ideas, he says. It was really helpful to learn how to conduct a customer discovery interview and really understand what your customer's needs are, he says.
He says 3D BioFibR also benefited from its participation in Creative Destruction Lab Atlantic, an objectives-based program for massively scalable, science- and technology-based companies hosted at Dalhousie. Chowdhry and the team learned how to pitch the company, secured an investor, and received advice on everything from strategy to IP to product development and marketing.
It provided a way to pressure test things in a safe environment, he explains. It's a room full of people who've been there, done that. You consistently get your assumptions tested and get feedback from people who have a pedigree.
As a result of that advice, 3DBioFibR has positioned itself as a biomaterial manufacturing company that can supply many different biomedical customers.
Chowdhry uses the examples of Gore-Tex and Intel to explain his companys strategy. Gore-Tex does not make clothing, but its material is used by many other companies to produce everything from gloves to boots. Intel doesnt make computers but its chips power countless PCs. Likewise, 3DBioFibRs collagen fibres can potentially be used by an array of biotech manufacturers.
In June 2023, in a significant step forward, the company signed a development deal with ReNerve, an Australian biotech outfit. 3DBioFibR has developed a prototype for ReNerve that will hopefully pending tests be used to help drive nerve regeneration. 3DBioFibRs collagen fibres would act as a cell migration highway in bridging severed nerves.
With our technology, we can make these collagen fibres at scale, with over 3,600 times the throughput of any competing technologies, Chowdhry notes. We can do 1,000 metres a second. And we can match the structure of native collagen so that cells can recognize and attach to the material in the way that they do in the body. The tissue engineering industry is all about creating these tissue constructs that can be eventually implanted into a human being.
According to Chowdhry, the tissue engineering industry is a $26-billion market, with companies and researchers pursuing applications spanning hair follicle regeneration, orthopedics, meniscus repair, and corneal, liver, and heart tissues, and even artificial ears.
3DBioFibRs product ready for market. (Provided photo)
Essentially the industry is trying to create implantable lab-grown tissue to put into a human for every potential condition, he explains. Anything in your body you can think of, there's at least one group working on creating it with implantable tissue.
According to Chowdhry, 3DBioFibRs technology is agnostic in terms of the tissue types it can pair with; it could potentially be used throughout the industry.
3DBioFibR now has 12 employees and manufactures its collagen fibre at its facility in The Labs by Invest Nova Scotia on Dalhousie campus. The company has raised three rounds of funding totalling $3.7 million and plans to pursue a Series A round in 2024.
We think our biomaterial will enable many new technologies to get to the next stage. So, the goal is to stay hyper-focused on improving production, quality, and efficiency, and by doing so, make the biggest impact across tissue engineering, Chowdhry concludes. Our fibres will hopefully help these technologies get closer to the clinic that's really the goal of the business.