The Prosser Lab - developing new therapies for the heart and brain.
Our lab interrogates the forces of the heart – the mechanisms that control how a heart cell generates force, and how force itself feeds back to regulate cell function and form. We leverage cellular biophysics and engineering, super-resolution imaging and cardiology to tackle the fundamental challenges of the mechanobiology of the heart. Our goal is to provide transformative insight into how the heart beats, and to inform new therapies for the treatment of heart disease.
The diagnosis of Dr. Prosser's daughter with STXBP1 encephalopathy also spurred the generation of a new therapeutic arm in the lab for neurological applications. We are developing novel, anti-sense oligonucleotide based therapies for the treatment of inherited neurodevelopmental disorders, such as those caused by mutations in STXBP1.
Julie Heffler’s work on how a balance of cytoskeletal forces maintains nuclear integrity in the cardiomyocyte earned cover honors for the Jan 2020 issue of Circulation Research. Congrats Julie, well deserved!
Congrats Matt – this work involved many overnight sessions conducting mechanical measurements on myocardial tissue preparations from transplant patients – when the heart often comes in around 2AM! But after all if it’s not hard, it’s probably not worth doing 🙂
An excellent, concise highlight in Nature Reviews Cardiology:
A longer piece by Medical News Today:
Christina’s paper on microtubules in human heart failure was published online in Nature Medicine. We found that suppressing stable microtubules can boost contractile function of heart cells from patients with heart failure – check it out: https://www.nature.com/articles/s41591-018-0046-2
Ben was honored with the Outstanding Early Career Investigator Award from the American Heart Association. Read all about it here: https://www.pennmedicine.org/news/news-releases/2017/july/cardiology-researcher-wins-aha-outstanding-early-career-investigator-award
Welcome Alex S., aka Xander/Ax, to the Prosser lab! Read more about Alex and our other lab members under the “People” tab.
Big congrats to Matt C. and Pat R., who were awarded post-doctoral fellowships from the American Heart Association and National Institutes of Health!
Who knew microtubules could be romantic? The HHMI celebrates cool science and heart puns. http://www.hhmi.org/biointeractive/tugging-cellular-heartstrings
Feb 11 - Feb 15
Join us at Biophysics in New Orleans, where Matt Caporizzo, Christina Chen, Julie Heffler, and Pat Robison will all be presenting their work. And eating beignets!
Jun 01 - Jun 30
The Prosser lab has a busy June discussing their work. Ben was lucky enough to present the lab’s work to two very different but fantastic audiences at the EMBO Microtubule Symposium in Heidelberg and at the Cardiac Gordon Research Conference in New Hampshire. Meanwhile, Pat and Christina presented at the Department of Physiology retreat right here in Philly.
Ben will also be presenting at the New Directions in Muscle Meeting in Florida later this month. Then maybe we’ll get back to work!
Our work was selected by NIH Director Francis Collins for his blog! Check out the story here, and look under the research tab for more in the popular press.
STATnews interviewed Dr. Prosser regarding our recent study on microtubule buckling in the heart. Check out the story here: http://us11.campaign-archive2.com/?u=f8609630ae206654824f897b6&id=beb156bae0
Science Daily also covered the story. Read about it here! https://www.sciencedaily.com/releases/2016/04/160421145756.htm
Our labs study on microtubule buckling in the heart was published in this weeks edition of Science. Congrats to Pat and all other authors involved. Read the study here: http://science.sciencemag.org/content/352/6284/aaf0659
Feb 27 - Mar 01
Biophysical Society Meeting – the lab will be traveling to Los Angeles, California for the annual Biophysical Society Meeting, where Drs. Prosser, Robison, and Caporizzo will all be presenting the labs work in different symposia and poster presentations.
We’re excited for the annual Pennsylvania Muscle Institute symposium, which will focus on recent advances in optical imaging and light microscopy (one of our favorite topics!). Xiaowei Zhuang, the driving force behind STORM microscopy, will deliver this years honorary lecture.
Julie Heffler's cover article in Circulation Research describes how a balance of cytoskeletal forces is required to maintain the integrity of the nucleus of the heart cell. Her work shows that desmin intermediate filaments and their attachments to the nucleus are critical for nuclear homeostasis, and shed light on how disruptions to desmin may lead to "desminopathies", a diverse group of cardiac and skeletal muscle disorders. Click on the link to view the full article!
Stiffening of the myocardium and diastolic dysfunction is a prevalent and intractable feature of several types of heart failure. Matt Caporizzo's work demonstrates that microtubules contribute to this stiffening in patient myocardial tissue, and that depolymerizing microtubules can improve diastolic mechanics. His work also indicates that the microtubule contribution to diastolic mechanics becomes less prevalent with large stretches and in heavily fibrotic tissue, where other factors likely contribute more to myocardial stiffness. This work helps refine a patient target population that may benefit from a microtubule based therapy. Click on the link for the full text!
Matt Caporizzo and Christina Chen provide a comprehensive review on the role of microtubules in the cardiomyocyte - their contribution to various homeostatic and mechanical functions in the cell, and how these may be altered in disease. The work also highlights the many unknowns regarding the diverse roles of microtubules in the heart. Click the link for full text!
Work by Chen et al. demonstrates two key findings: 1) that there is a proliferation and stabilization of microtubules and intermediate filaments in human heart failure, regardless of disease origin. 2) that suppressing detyrosinated microtubules with either genetic or pharmacologic approaches can rescue the contractile function of heart cells from patients with heart failure, about 40-50% back to "normal." This work highlights detyrosinated microtubules as a promising therapeutic target for the treatment of heart failure.
Click on the link to read the paper, or check out the press release here : http://www.newswise.com/articles/view/695927/