Maria E Gaczynska, PhD

Research interests of the Maria Gaczynska – Pawel Osmulski wife-husband team, span areas from biophysical properties of cells to dynamic properties of proteins. The overarching themes are: how cells descend from healthy to diseased? How the dynamic transitions of proteins determine their vital properties? Our major projects:

1. Circulating tumor cells (CTCs) shed from tumor to blood are seeds of deadly metastasis (see images of patient-isolated CTCs and their immune cells companions on the 2021 Cancer Research cover). We found that these cells have peculiar mechanical properties that allow them to survive and thrive in circulation. We are exploring mechanical properties of CTCs in prostate and lung cancers to:

 (i) learn about mechanisms of metastasis,

(ii)  design biophysical biomarkers to prognose and predict cancer progression and resistance to drugs.

2. Ubiquitin-proteasome system and its major protease, the proteasome, are responsible for majority of intracellular regulated proteolysis and are major keepers of proteostasis (the balance between protein anabolism and catabolism). The proteasome is a giant, multi-subunit, multifunctional and modular enzyme. We are exploring properties of the proteasome to design its allosteric regulators that could:

(i) restore proteostasis in cells that cannot keep up with protein degradation – useful to curb neurodegeneration in Alzheimer’s or Parkinson’s disease,

(ii) restore proteostasis in muscle cells during muscle wasting (cancer and other severe diseases, aging, immobilization),

(iii) trip proteostasis to kill rogue cancer cells without harming neighboring healthy cells.

To reach the goals we are using multiple structural biology, cell biology and biophysics methods, including Atomic Force Microscopy to interrogate single molecules (protein dynamics, interactions between biomolecules) and single cells (mechanical phenotyping, cell-cell interactions, chemical imaging).