About

Michael Ostap, Ph.D., is a Professor of Physiology and the Director of the Pennsylvania Muscle Institute at the University of Pennsylvania's Perelman School of Medicine. His research focuses on understanding the cellular machinery responsible for powering cell movements and shaping the architecture of cells, tissues, and organs. His discovery-based research emphasizes the role of the cytoskeleton, molecular motors, and signaling pathways in processes such as cell migration, muscle contraction, and intracellular transport. These pathways are crucial for normal and pathological processes including cell and tissue development, endocytosis, wound healing, immune response, cardiomyopathies, and tumor metastasis. His laboratory investigates cytoskeletal motors like myosin, dynein, and kinesin, which utilize chemical energy in the form of ATP to generate mechanical force and motion. The research aims to determine how these motors function at the molecular level, how they are connected to cellular machinery, how they are regulated, and how their biophysical parameters impact cell function. Dr. Ostap employs biochemical, cell biological, single-molecule, and other biophysical techniques to better understand these proteins in health and disease.

Research topics

• Computer Science
• Biophysics
• Biology
• Chemistry
• Machine Learning
• Physics
• Artificial Intelligence
• Mechanical engineering
• Environmental science
• Engineering
• Optoelectronics
• Biochemistry
• Remote sensing
• Biological system
• Geography
• Optics
• Materials science

Selected publications

• Myosin mutants in the optical trap

  2024

  • Computer Science
  • Materials science
  • Optoelectronics

  Hypertrophic cardiomyopathy (HCM) is a symptomatic affliction due to mutations in cardiac contractile proteins. We compared a highly penetrant mutation in cardiac myosin, M493I, with wild type (WT) using an advanced optical trap assay capable of quantifying kinetic rates including actomyosin re-attachment. Kinetic changes in both the actomyosin attachment and detachment rates suggest that the equilibrium between a conformation termed the Interacting Head Motif (IHM) and freely available myosin heads is disturbed in M493I. This type of disruption has been hypothesized to lead to the toxic hypertrophy observed in patients.

  PublisherDOI

• Advances in optical trap studies on actomyosin that enable reliable measurement of attachment kinetics

  2023

  • Computer Science
  • Machine Learning
  • Biological system

  Imprecision in protein positioning and instrument dead time have hampered efforts to measure macromolecular association rates in optical trap assays. Here, we combine several technical improvements to the three-bead optical trap assay, including precise protein deposition, enhanced stage stability by feedback, and improved data filtering. These enhancements allow us to precisely and reliably detect interactions between cardiac heavy meromyosin (cHMM) and actin and quantify attachment and reattachment rates. These studies providing insights into strain-dependence of the power stroke and a proposed transition from super-relaxed (SRX) to disordered relaxed (DRX) states, which is thought to be disrupted in human hypertrophic cardiomyopathy.

  DOI

• Abstract 2669: Off-axis power-stroke and force sensing features of myosin-IC revealed by high-resolution cryo-EM

  Journal of Biological Chemistry · 2023

  • Computer Science
  • Artificial Intelligence
  • Biophysics
  DOI

• Myosin modulators: emerging approaches for the treatment of cardiomyopathies and heart failure

  Journal of Clinical Investigation · 2022 · 64 citations

  • Medicine
  • Pharmacology
  • Cardiology

  Myosin modulators are a novel class of pharmaceutical agents that are being developed to treat patients with a range of cardiomyopathies. The therapeutic goal of these drugs is to target cardiac myosins directly to modulate contractility and cardiac power output to alleviate symptoms that lead to heart failure and arrhythmias, without altering calcium signaling. In this Review, we discuss two classes of drugs that have been developed to either activate (omecamtiv mecarbil) or inhibit (mavacamten) cardiac contractility by binding to β-cardiac myosin (MYH7). We discuss progress in understanding the mechanisms by which the drugs alter myosin mechanochemistry, and we provide an appraisal of the results from clinical trials of these drugs, with consideration for the importance of disease heterogeneity and genetic etiology for predicting treatment benefit.

  DOI

Frequent coauthors

• Donald A. Winkelmann

  Rutgers, The State University of New Jersey

  2 shared

• Yale E. Goldman

  2 shared

• Henry Shuman

  California University of Pennsylvania

  2 shared

• Robert C. Cail

  University of Pennsylvania

  2 shared

• Luther W. Pollard

  University of Pennsylvania

  1 shared

• Richard Wike

  1 shared

• Serapion Pyrpassopoulos

  University of Tübingen

  1 shared

• Małgorzata Boczkowska

  University of Pennsylvania

  1 shared

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