Justin Parreno

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The Parreno Lab is unravelling the biological mechanisms linking mechanical signalling to diseases such as tendinosis

Justin Parreno

Tendons are fibrous connective tissues that enable movement by transmitting mechanical forces from muscle onto bone. While tendon loading during exercise such as strength training, running, or cycling can cause positive adaptation, high loads on tendon can cause tendinosis (tendon degeneration). Tendinosis is common and notoriously difficult to treat. Often, asymptomatic tendinosis precedes tendon rupture which can be debilitating. The cellular mechanisms implicit in tendinosis progression are not known.

The Lab: The Parreno/Elliott collaboration is funded by a $2.4 million R01 from the National Institutes of Health which has led to the development of complementary in vivo (rodent model), ex vivo (tissue model), and in vitro (cell culture) approaches to determine the mechanical and cellular mechanisms of tendinosis. Within this proposal, the Parreno lab aim's to determine the role that the actin-based signaling mechanisms play in sensing physiological mechanical loads and how such signaling mechanisms are compromised in tendinosis due to tissue overload. Their recent findings lend support to a long hypothesized mechanotransmission paradox that overloading of tendon leads to under-stimulation of tendon cells, tenocytes. They suspect that tendon overloading disrupts integrins, which connect cells to the tendon matrix. This disconnection of cells from matrix results in cells no longer being able to sense subsequent mechanical loads. As a result of this cellular under-stimulation, the tenocyte actin cytoskeleton destabilizes, which the Parreno lab is showing to play a pivotal role in tendinosis (see figure). They demonstrate that actin is more than just a structural protein and has the ability to directly regulate key genes involved in Tendinosis.

In addition to tendon disorders, the Parreno lab studies other conditions - Osteoarthritis, Cataracts, and Presbyopia. These projects involve collaborations with local, national and international academic laboratories and clinicians. Additionally, the Parreno lab collaborates with industry partners on improving therapies for joint disease as well as vaccine delivery. While the projects in the lab are diverse, they are linked by elements of mechanical loading and regulation by the actin cytoskeleton. The overall vision of the lab is to develop actin-based therapies against diseases.

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tendon cell

Under-stimulation of tendon cells results in alterations in actin organization. Globular (G-) actin monomers (green) polymerize to form filmentous (F-) actin (red). When tendon cells are under-stimulated (bottom), we see an increase in the proportion of G-actin suggesting that under-stimulation destabilizes F-actin. This leads to tendinosis-like gene changes.

In addition to this new NIH funding, the Parreno lab is supported by a Delaware Center for Musculoskeletal Project Grant, a University of Delaware Strategic Initiative Grant, and an NIH-R01 grant on the lens in collaboration with Velia M. Fowler, Chair of Biological Sciences.

The PI: Dr. Parreno is committed to training student scientists spanning across many disciplines (Biology, Bioengineering, Mechanical Engineering, Chemistry, Medical Diagnostics, and even Economics) and promotes Scientific success to students at the University of Delaware. When he arrived at UD, he initiated a 'Lens Club' where Ocular researchers at the University meet monthly to discuss research projects. He serves as the Biology Undergraduate Research Director and works with other faculty to improve Biology undergraduate and graduate student research experiences.

Beyond the University of Delaware, he mentors trainees at all levels from post-doctoral research associates to high school students. He is a mentor to a post-doctoral research associate through an Orthopaedic Research Society Collaborative Research Exchange grant, and an academic advisor to three high-school capstone project students through Allied Health Academy in New Jersey. He strives to foster scientific study and careers to groups underrepresented in STEM, serving as a mentor to PhD students through the Association of Filipino Scientists of America (AFSA), as a faculty consultant for GradMAP Philippines STEM Mentorship Network, and as the University of Delaware's Filipino Students Association Faculty Advisor.​​

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