|
|
|
|
|
 |
Overview
The mission of our research is to bring clarity ot the field of muscle regulation (in particular) and biological information processing (in general). We do this by proposing bold quantitative models of function (obtained through creative reflection) and careful measurements on samples of high quality (obtained through hard work).
Objectives and Methods
The long-term research aim of my laboratory is to find a treatment for diastolic congestive heart failure, a condition where the relaxation of the heart is impaired. Congestive heart failure affects 5.7 million Americans. Heart failure manifests as impaired activation or deactivation of the heart at the level of the myofilament. The cardiac myofilament is the elementary structural unit in the heart for producing Ca2+-regulated contractile force.
Due to its clinical significance, the cardiac myofilament is the subject of intense investigation; studies are aimed at defining its operation, defining its role in the pathophysiology of heart failure, and identifying promising strategies for treating heart failure. A central question in the field of muscle regulation is how the various components of the myofilament communicate allosterically at the kinetic, energetic and structural level to rapidly activate and inactivate contractility. Of particular interest is how the myosin motors themselves contribute to their own regulation, a phenomenon called activation-dependent regulation. The aim of our current research is to reveal the mechanism of activation-dependent regulation in terms of energetics, kinetics, and structure. The problem is important not only because activation-dependent regulation is central to cardiac regulation but also because mechanical and chemical signals such as cell stretch, neurohormonal and redox regulatory pathways manipulate activation-dependent regulation to tune contractility to meet the needs of the body.
Our studies involve both experimental measurements and multi-scale modeling. We use Fluorescence Resonance Energy Transfer (FRET) measurements to study functionally significant conformational changes in the myofilament during activation and deactivation. Our FRET measurements are at the “single molecule” level, where we are study myofilaments one at a time. Single molecule FRET is a leading method in nanobiology. Our experimental studies inform multi-scale modeling of allostery within the myofilament and between myofilaments. Our mesoscopic modeling has led to a physiological model that explains a long-standing paradox in muscle regulation: why and how both Ca2+ and ATP are required to effect signaling in the myofilament. We believe that this model represents a general design solution that enables the efficient operation of modularly constructed supramolecular assemblies such as the cardiac myofilament. More recently, we have expanded our modeling studies to include all atom molecular dynamics (MD) simulations.
In addition to our basic research on the myofilament, we use the cardiac myofilament to address fundamental questions in biochemistry relating to signal transduction within ligand-regulated protein assemblies.
Interesting facts
-
"Coronary artery disease (CAD) is the most common cause of death, by far, in the United States, killing ten times more women than breast cancer." USMLE Master the Boards Step 3, p39.
-
"Coronary heart disease (CHD) is the cause of about half of the deaths in the United States." Lippincott's Illustrated Reviews, Pharmacology (4th ed). p249.
|
|
News |
Future
Present
-
LAB: Congratulations: Tanya, Casi, and Brent received 2012 Joseph F. Nelson Undergraduate Fellowships! Among 28 appliations, 5 were selected,
-
LAB: Jenna Guthmiller joins the lab
-
LAB: Openings: research assistant professor, postdoc
-
Movie of cultured cardiomyocyte spontaneously contracting
Past
-
March 2012 JMR: Talk, Integrative Biological Sciences, University of South Dakota.Host Dong Zhang
-
2/12 LAB: BPS, San Diego CA
-
6/22/11 LAB: Romain Souspault, visiting graduate student, joins the lab for summer internship.
-
6/21/11 LAB: Bing Sun, MD, PhD joins the lab.
-
5/23/11 LAB: Gi-Ho Kim, PhD joins lab as Senior Research Associate.
-
12/12/10 JMR: Invited Lecture. "Medical ontologies" Brookings Health System, Brookings SD.
-
12/10: LAB: Tyrel Deutscher joins the lab.
-
12/10: LAB:Brandon Breitling joins the lab.
-
12/10: LAB: Danica Ommen joins the lab.
-
12/10: LAB: NIH-RO1 awarded: "Allosteric Regulation of Myocardial Contraction"
-
11/10: JMR: AMIA Meeting, Washington DC.
-
9/9/10 LAB: Featured on OnCall (SD PBS)
-
8/30/10 JMR: Teaching: Biochemistry 1 (CHEM464) Lecture notes
-
8/16/10 LAB: Jeremy Ball, Graduate Student in Math & Statistics, joins lab.
-
8/10/10 JMR: Invited lecture. "eTenum-a knowledge-based startup business in medical informatics," talk at Brookings Rotary, Brookings, SD.
-
8/4/10 LAB: Maria E. Moutsoglou, Chemistry Graduate Student, joins lab.
-
8/2/10 LAB: Welcome Francisca Egyir, Chemistry Graduate Student and first student in the SDSU Training Program in Biological Signaling.
-
JMR: Lake Poinsett Sailing Academy webpage.
-
5/23/10 JMR: myofilament meeting (madison, wi.)
-
4/10 LAB: Mike Krsnak receives Tanaka Fellowship
-
2/10 LAB: Troy Lackey, Research Assistant, joins the lab
-
2/10 LAB: annual biophysical society meeting
-
2/10 LAB: Brian Moore PhD, server administrator
-
2/10 JMR: seminar at SDSU Pharmacology
-
1/10 LAB: Mike Krsnak, Biochemistry Undergraduate, joins the lab
-
1/10 JMR: BIOS/Photonics West meeting
-
1/29/10 JMR: seminar at SDState, life sciences
-
1/10 JMR: The lab moved to the Department of Chemistry/Biochemistry at South Dakota State University. See photos
-
11/09 JMR: 2 talks at IBM (Yorktown Heights, NY)
|
| |
|
|
|
