Cellular and molecular mechanisms involved in therapeutic application
A current bottleneck exists within the transition from research to medicine. Our eclectic collaboration merges four independent, but related, research interests focused on understanding the cellular and molecular mechanisms involved in therapeutic application. By examining cellular mechanics of disease states, our first interest aims to understand how gene regulation can be controlled by spatiotemporal changes and other mechanical properties of cells. Gene regulation within this system has been shown to induce a disease phenotype defined by cellular apoptosis. Another interest examines factors related to apoptosis that control the balance between replicative senescence and self-renewal as potential therapeutic targets. We have developed a defined environment characterized by low oxygen and growth factor supplementation leading to increased cellular lifespan. A third interest employs low oxygen and growth factor supplementation to exploit increased cellular lifespan that can be used bypass current methods plagued with limited replicative capacity. This system is used to create cell-derived tissue rings for artificial blood vessels. The importance of a sterile environment for successful transplantation is mediated by our fourth interest, which aims to understand how antimicrobial peptides can aid in transplantable therapeutics, such as engineered blood vessels. Separately each of these interests investigates an independent therapeutic challenge that can offer cellular and molecular tools for designing diverse treatment strategies.
Jerome Baudry
Faculty: Project Co-PI
Hello,
What is the potential commercial outcome of your technical work, how is the entrepreneurial dimension of the project affecting/driving the decision process of the project?
Sarah Runge
Thanks for your question. Decision making processes are driven by applying our research to fulfill needs within the community. We have a multidisciplinary team that focuses on collaboration. Currently, we are working on research development to commercialize tissue engineered vascular grafts and implantable antimicrobial peptides for prevention of post-operative infection. Our training involves interaction and networking with small business owners, CEOs, and angel investors in the field. One of these events is entitled TAN, short for ‘technical advisor network’, in which a panel of advisors, who are established business leaders and professors give input on our elevator pitch. We are being trained to see the commercialization potential of our work in various aspects so that we can bridge the gap between basic research and product development.
Govindarajan Ramesh
Faculty
Hi!
How does a low oxygen environment influence population doubling?
Karen Levi
Graduate Student
Thanks for the question. Our data show that culturing primary human smooth muscle cells in a low oxygen environment decreases the population doubling time. However, even more important to us is that senescence is delayed under low oxygen culture conditions and can result in 5 additional population doublings. In addition, there seems to be no effect on the differentiation of these cells to the contractile phenotype, even after several weeks of culture in low oxygen. Currently, we are unsure what cellular mechanisms are affected by low oxygen culture to induce these changes in population doubling rates. Our work to determine the full effect of low oxygen culture on the proliferative capacity of primary human smooth muscle cells and the pathways that lead to the observed phenotype is still ongoing. Collaborators are currently working to implicate molecules critical for the phenotype of these cells. Several interesting molecules have already been identified and work is being done to experimentally determine that those molecules play a role in increasing time to cellular senescence.
Govindarajan Ramesh
Faculty
Hi!
How does a low oxygen environment influence population doubling?
Markus Seeliger
Faculty: Project Co-PI
Do you interact with clinical faculty on the potential applications of these exciting new technologies?
Heather Cirka
Graduate Student
Thanks for your question. Currently we are in the research and development phase of making this technology commercializable. Although at this time we are not directly working with any clinical faculty, our advisors have strong relations with clinical faculty and expertise with animal models. Specifically, Dr. Glenn Gaudette is involved in collaborative projects with surgeons at Harvard Medical School and Brigham and Women’s Hospital. Dr. Kristen Billiar is an advisor to orthopedic surgeons at the University of Massachusetts Medical School. In addition to being professor of biology and biotechnology, Dr. Tanja Dominko has a doctorate veterinary medicine. Although interactions with clinical faculty are not guiding the decision process of research avenues at this time, such resources and expertise is readily available to us.
Zhaomin Yang
Faculty
Could surfaces be coated with derivatives of antibiotics instead of antimicrobial peptides and would such coatings be effective?
Todd Alexander
Graduate Student
Surfaces could be coated with derivatives of antibiotics instead of antimicrobial peptides. Different groups have used quaternary ammonium salts, vancomycin and various other antimicrobials. These systems have demonstrated efficacy. The trick is to find the right derivative and binding chemistry. The binding site, tether flexibility and tether length are all important factors that affect the efficacy of the system.
Kristin Hager
Partner: Outreach
Hi,
Will you be using high throughput microscopy to assay your cells and what does flourosectroscopy mean?
Todd Alexander
Graduate Student
I use LIVE/DEAD® BacLight™ Bacterial Viability Kits in order to stain my cells. I may not be using the right term but I look for fluorescence under different filters. I determine the killing percent using Image J. At this time I do not have plan to use high throughput microscopy but perhaps in the future I will.