Programs
Departments & Divisions
Research Areas
Cancer Longevity & Aging NeuroscienceMaria E Gaczynska, PhD
Associate Professor
Subspecialties: biophysics, biochemistry, cancer biology, scanning probe microscopy, drug design, protein allostery, mechanisms of metastasis
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).
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Professional Background
Education
- 1997 - Postdoctoral Fellowship - Cancer Biology - Massachusetts Institute of Technology, Center for Cancer Research
- 1995 - Postdoctoral Fellowship - Cell Biology - Harvard Medical School
- 1991 - Postdoctoral Fellowship - Immunology and Microbiology - University of Arizona College of Medicine
- 1990 - BS - Physics - Nicolaus Copernicus University
- 1990 - Postdoctoral Training - Senior Researcher, Department of Biophysics - University of Lodz
- 1989 - PhD - Biophysics - University of Lodz
- 1985 - MS - Molecular Biology - University of Lodz
Appointments
- 9/2005 - Associate Professor - University of Texas Health Science Center at San Antonio, Molecular Medicine, San Antonio
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Instruction & Training
- Present, MMED 5020 Research Practicum, Course Director, University of Texas Health Science Center at San Antonio
- Present, CSAT 6069 Cancer Biology Core 2: “Ubiquitin-Proteasome System and Cancer” (4 hrs), University of Texas Health Science Center at San Antonio
- Present, INTD 5007, Module INTD 6009 Advanced Cell and Molecular Biology, Advanced Molecular Biology Module, “Protein synthesis, posttranslational modifications and proteolysis” module (8 hrs) in the core IMGP course, University of Texas Health Science Center at San Antonio
- Present, MMED 5015 Modern Methods/Cell Molecular Biology, “Molecular Imaging”’ (2 hrs), University of Texas Health Science Center at San Antonio
- Present, IBMS 5000 Fundamentals of Biomedical Sciences: “Atomic Force Microscopy: from Molecules to Cells” (1hr), University of Texas Health Science Center at San Antonio
- Present, MMED 6016 Advanced Molecular, Cellular and Synthetic Biology “Protein synthesis, processing, targeting and degradation” and “Synthetic Biology” (10 hrs total; the latter 2-hours lecture shared with Dr. Osmulski), University of Texas Health Science Center at San Antonio
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Research & Grants
- Design of allosteric regulators of the proteasome with a focus on anti-cancer, anti-neurodegeneration (Alzheimer's disease) and anti-inflammatory drug candidates.
- Elucidating mechansms of cancer metastasis with a focus on the role of physical cues in cancer spread and the goal to design biophysical biomarkers for cancer progression and drug resistance.
- Atomic force microscopy studies on molecular (protein dynamics) an cellular (mechanical phenotypes of cells) levels.
Grants
Active:
Title: Novel proteasome-activating compounds for treatment of Alzheimer’s disease.
Major Goals: Our goal is to develop peptoids compounds to activate the proteasome and restore proteostasis in neurons failing with Alzheimer’s disease.
Name of PI: Gaczynska, Maria and Osmulski, Pawel
Source of Support: Owens Medical Research Foundation
Primary Place of Performance: San Antonio
Project/Proposal Start and End Date: 05/01/23 - 04/30/25
Title: Proteasome dysfunction as a driver of age-associated risk for Alzheimer’s disease onset and progression.
Major Goals: The goal is to test proteasome-directed molecular and pharmacologic interventions to attenuate effects of Alzheimer’s disease.
Project Number: 1RF1AG065301-01A1
Name of PI: Pickering (PI) Gaczynska (PI of subcontract)
Source of Support: NIH- NIA
Primary Place of Performance: San Antonio
Project/Proposal Start and End Date: 09/30/2020-08/31/2024
Title: How to stop the fatal attraction between circulating tumor cells and macrophages?
Major Goals: Our goal is to test the hypothesis of chemokine-propelled vicious cycle in a cell culture model of CTCs microenvironment.
Name of PI: Gaczynska
Source of Support: Morrison Trust
Primary Place of Performance: San Antonio
Project/Proposal Start and End Date: 10/1/22-9/30/23
Title: Molecular mechanisms of gap junction promotion of lesion formation in Endometriosis
Major Goals: The goal is to elucidate molecular mechanisms critical for cell-cell interactions in endometriosis.
Project Number: 1R01HD109027-01
Name of PD/PI: Nicholson, Bruce J. (Gaczynska: Co-I)
Source of Support: NICHD
Primary Place of Performance: University of Texas Health Science Center at San Antonio
Project/Proposal Start and End Date: 09/17/2021-06/30/2026
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Service
School
CGM Discipline Executive Committee
IBMS Admissions Committee
Graduate School of Biomedical Sciences Awards Committee
Service to the Profession
Selected, recent
2023-present Associate Editor in Frontiers in Molecular Biosciences
2022 Innovation Talk, TechConnect World Innovation Conference & Expo, National Harbor, MD
2022 Grant reviewer for The Polish Science Foundation
2021-present Reviewer for American Heart Association
2021 Grant reviewer for The Dutch Research Council
2019-present Editorial Board of Biomolecules
2017 Grant reviewer for the Israel Science Foundation
2015, 2017 NIH ad hoc reviewer: F05 (2015), NCI ZCA1 (2017)
2014, 2015 The Wellcome Trust (UK) grant reviewer
2012 Invited Speaker, 3rd Kanazawa Bio-AFM Workshop, Kanazawa, Japan
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Publications
- Genetic and pharmacologic proteasome augmentation ameliorates Alzheimer’s disease-like symptoms through increased turnover of β-
- Soluble pathogenic tau enters brain vascular endothelial cells and drives cellular senescence and brain microvascular dysfunctio
- Electronic Circular Dichroism Detects Conformational Changes Associated with Proteasome Gating Confirmed Using AFM Imaging
- A Role for the Proteasome Alpha2 Subunit N-Tail in Substrate Processing.
- Contacts with Macrophages Promote an Aggressive Nanomechanical Phenotype of Circulating Tumor Cells in Prostate Cancer
- Androgen deprivation-induced elevated nuclear SIRT1 promotes prostate tumor cell survival by reactivation of AR signaling
- Single-Cell Proteomic Profiling Identifies Combined AXL and JAK1 Inhibition as a Novel Therapeutic Strategy for Lung Cancer
- New Peptide-Based Pharmacophore Activates 20S Proteasome
- Inhibitory Interplay of SULT2B1b Sulfotransferase with AKR1C3 Aldo-keto Reductase in Prostate Cancer
- Pipecolic esters as minimized templates for proteasome inhibition
- Proline- and Arginine-Rich Peptides as Flexible Allosteric Modulators of Human Proteasome Activity
- Adipokines Deregulate Cellular Communication via Epigenetic Repression of Gap Junction Loci in Obese Endometrial Cancer
- Small Molecule Modulation of Proteasome Assembly
- Targeting Protein-Protein Interactions in the Ubiquitin-Proteasome Pathway