About The Prosser Lab

With each heartbeat, the mechanical stress of heart cell contraction and relaxation is converted into intracellular signals through a process termed "mechanotransduction". While critical for the heart's normal adaptive response to changing demands, faulty stress-sensing is intimately linked to heart disease. Despite this importance in human health, the cellular mechanisms of mechanotransduction remain poorly understood. The goal of our lab is to unravel molecular mechanisms of mechanotransduction in the heart and other tissues. We combine novel techniques to manipulate mechanical stress and strain at the single cell level with high-speed and super-resolution imaging to evaluate sub-cellular responses to mechanical stimuli. Current projects in the lab seek to understand how the cytoskeleton functions to sense and transmit these mechanical signals, and the consequences of this mechanical stress transmission on cardiac health and disease.


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News and Upcoming Events

Ben wins AHA Outstanding Early Career Investigator Award

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!

Welcome Alex S., aka Xander/Ax, to the Prosser lab!  Read more about Alex and our other lab members under the “People” tab.

Congrats Matt and Pat!

Big congrats to Matt C. and Pat R., who were awarded post-doctoral fellowships from the American Heart Association and National Institutes of Health!

Tugging on the heart strings this Valentine's day

Feb 14

Who knew microtubules could be romantic?  The HHMI celebrates cool science and heart puns.  http://www.hhmi.org/biointeractive/tugging-cellular-heartstrings

 

Biophysics in NOLA

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!

Conferences Galore

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!

NIH Director blog on microtubule buckling in the heart

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.
https://directorsblog.nih.gov/2016/05/03/a-look-inside-a-beating-heart-cell/

Media Coverage of Robison et al., Science 2016

Apr 23

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

Prosser Lab study published in Science!

Apr 22

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

Biophysical Society Meeting

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.

PMI Symposium

Jan 11

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.

Trip to Baylor College of Medicine

Nov 23 - Nov 24

Dr. Prosser will present our work and meet with the faculty at Baylor, leaders in the study of striated muscle disease.

Visit to UC Davis

Oct 19 - Oct 21

Dr. Prosser will present our work and meet with faculty in the departments of Physiology and Pharmacology at the University of California Davis, a stronghold of cardiac signaling research.

France!

Sep 03 - Sep 05

Dr. Prosser will be visiting the Institut des Neurosciences (Grenoble, France – part of INSERM) to visit colleagues and present work from our lab. And then spend a little down time in Paris.

Webinar on new "Airyscan" imaging technology

Jun 22

Dr. Prosser will be a guest speaker in a webinar sponsored by Carl Zeiss Microscopy describing the lab’s experiences with “airyscan,” a new imaging modality that provides fast, high-resolution light microscopy that is optimized for live cell imaging.
Dr. Prosser will be one of three guest speakers along with Drs. Peter O’Toole and Jennifer Lippincott-Schwartz.

Recent Research

Detyrosinated microtubules buckle and bear load in contracting cardiomyocytes


Our work, in collaboration with folks in Engineering (Caporizzo, Shenoy groups) and Medicine (Margulies), shows that microtubules buckle and bear compressive load in a beating cardiomyocyte. The ability of microtubules to function as molecular shock absorbers is graded by "detyrosination", a post-translational modification of tubulin. Further, we found that detyrosination is increased in cardiomyopathy and correlates with functional decline in certain patient populations. The Prosser lab is actively investigating the efficacy of targeting detyrosination therapeutically to improve cardiac function in heart disease. Patrick Robison is the first author on this manuscript published in Science (a full text link is provided below).

Press for microtubule buckling in the heart!


Our work on microtubules as molecular "struts" or "shock absorbers" in the beating heart has been featured in the popular press, and in the blog of NIH director Francis Collins. Check out a sampling below:
NIH director blog: https://directorsblog.nih.gov/2016/05/03/a-look-inside-a-beating-heart-cell/
Gizmodo: http://gizmodo.com/microscopic-tubes-inside-beating-heart-cells-work-like-1774530830
Business Insider: http://www.businessinsider.com/a-rare-view-inside-a-beating-heart-cell-2016-5

Super-Resolution View of Cardiac Microtubules


Current work in the lab is focused on the microtubule cytoskeleton and how it regulates the mechanobiology of heart cells. We are using novel techniques to manipulate and measure cell stress while using advanced imaging to examine how these stresses influence intracellular processes.

Image: STED super-resolution microscopy reveals intricate details of microtubule networks in the heart.

Roles of Cardiac MyBP-C


In this work we describe a novel function for the cardiac regulatory protein MyBP-C, whose role has remained elusive. We propose that MyBP-C (red), which localizes to the sarcomere distant to the sites of calcium release (green), increases the calcium sensitivity of the contractile apparatus at this distant site in order to offset any non-uniformity in the calcium dependent activation of the sarcomere.

Image: Image acquired using STORM super-resolution imaging.