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.
On January 1st 2021 we officially kicked off the Leducq Cytoskeletal Network (LCN). This Trans-Atlantic Network of Excellence brings together 7 different labs from the U.S. and Europe all working to better understanding how the cytoskeleton contributes to normal and pathological functions of heart muscle cells, and to develop new therapies for the treatment of heart disease. The network will be led by Dr. Prosser from Penn and Dr. Lucie Carrier from Hamburg. For more details check out the press release under recent research.
We’re thrilled to have entered into a sponsored research agreement with Ionis Pharmaceuticals, the leading experts on antisense technology. The partnership will be between Ionis and the Prosser and Davidson labs at Penn and CHOP, respectively, and is focused on testing a new approach to treat STXBP1 disorders using antisense oligonucleotides.
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
Dr. Prosser will co-lead a Leducq Transatlantic Network of Excellence on the cytoskeletal role in cardiomyocyte health and disease. Leducq networks brings together investigators from all over the world to tackle the leading challenges in cardiovascular research.
Our network consists of the labs of Drs. Ken Margulies (Penn), Giulio Agnetti (Hopkins) and Ben Prosser (Penn) in the U.S., and Drs. Lucie Carrier (co-lead, Hamburg), Jolanda van der Velden (Amsterdam), Izhak Kehat (Israel) and Marie-Jo Moutin (France). Sabrina Benitez at Penn will function as the network administrator. For more on our mission, check out the press release at the attached link.
Three recent publications from our lab and collaborators shed insight into how physical forces affect the shape and function of cardiomyocyte nuclei, with a specific focus on the nuclear lamina. The first study, led by the Discher lab (Cho et al., Dev Cell 2019), describes how the nuclear lamina acts to sense its mechanical environment and protect the nucleus from mechanical stress. Our work (Heffler et al. Circ Res 2020) went on to show how microtubules and intermediate filaments maintain a force balance on the lamina, and how disrupting desmin compromises this balance and leads to nuclear collapse. The most recent work, led by the Jain lab (Cell Stem Cell 2021), reveals how pathogenic variants in LMNA (the gene that encodes for the core structural element of the lamina) disrupt interactions between the lamina and chromatin to drive tissue-specific pathologies. Check out the papers in the links below.
We're thrilled to announce the formation of the ENDD Therapeutics Team, a multi-disciplinary group of investigators focused on developing new therapies for Epilepsy and Neuro-Developmental Disorders (ENDD).
The core labs include the Prosser and Heller Labs at Penn and the Davidson Lab at CHOP. We also work closely with Debbie French and the Human Pluripotent Stem Cell Core at CHOP to develop iPS-models of NDD and test novel therapies, and with Dr. Ingo Helbig, a neurogeneticist at CHOP, as our clinical consultant.
The group is focused on developing anti-sense oligonucleotide (ASO), small molecule, and CRISPR-based strategies for the treatment of NDD, with our initial focus on STXBP1- and SYNGAP1-related disorders. The ENDD team is supported by collaborations with the pharmaceutical and biotechnology sector, private foundations including the Syngap Research Fund and STXBP1 Foundation, and philanthropic efforts.
Our team has developed a novel antisense approach to increase gene products that cause disease due to haploinsufficiency. We use site-blocking oligonucleotides (SBOs) to prevent microRNA-based repression of a target gene, "releasing the brake" on a particular gene of interest that is deficient in pathological states. In proof-of-concept studies, we show how disrupting microRNA repression of STXBP1 is capable of upregulating gene and protein expression to levels that are predicted to be therapeutic. We are currently pursuing this strategy for genes that cause neurodevelopment disorders due to haploinsufficiency. Check the linked abstract to see more!