Joshua Z. Gasiorowski, Ph.D.

Assistant Professor


Dr. Joshua GasiorowskiMidwestern University
College of Health Sciences
Department of Biomedical Sciences
Science Hall 203-C
555 31st St.
Downers Grove, IL 60515

Office: 630-515-7614
e-mail: mailto:jgasio@midwestern.edu

 

 

EDUCATION
B.S.      Molecular Biology                      Benedictine University (IL)      2000
Ph.D.    Molecular Biology & Genetics      Northwestern University         2006

RESEARCH SUMMARY

The basic science of regenerative medicine

The tissue engineering and gene and cellular therapy technologies that comprise the broad field of regenerative medicine have held tremendous promise for decades, but they have not yet met expectations.  FDA approved gene therapy treatments remain elusive and there has been limited success creating clinically useful engineered tissues.  Many of these technologies fail in the clinic because experimental therapies are often derived from in vitro models that lack the biochemical and biophysical signals that cells are exposed to in vivo.  The work in my lab is focused on understanding and directing basic regenerative processes that occur when cells are exposed to synthetic extracellular matrix scaffolding materials and therapeutic transgenes.

Research projects

Project I: We are developing embeddable hydrogels with several materials that act as an extracellular matrix scaffold to permit adult stem cell infiltration and support cell growth.  Through the use of positively charged and DNA-intercalating peptides, the hydrogels can bind DNA plasmids and actively release them with an electrically charged trigger. Triggered release and delivery of differentiating DNA vectors specifically within the targeted material can reprogram adult stem cells and drive the de novo generation of minimally immunogenic engineered tissue in vivo.  The advantage of this system is that it primes the endogenous cells to remodel and vascularize the biomaterial as it becomes populated over time.  It also incorporates non-immunogenic naked DNA instead of viral vectors or toxic polycationic DNA complexing reagents.  As this technique is refined, it can be used as a strategy to treat a variety of diseases with a cell and gene therapy approach.

Project II: Cells are complex sensors that can detect and respond to a seemingly endless array of extracellular signals. While many of these signals are biochemical in nature, cell behaviors can also be modulated by biophysical cues. We employ several nano- and micro-scale engineering techniques, such as self-assembly of polymers and soft lithography, to fabricate biomimetic substrates that allow us to characterize cell responses to biophysical cues in controlled, reproducible in vitro environments. Understanding these processes can help us elucidate basic science mechanisms in the fields of mechanotransduction, cell biology, development, and differentiation.  We employ a variety of topographically patterned substrates to direct cell proliferation, migration, and gene expression for neuronal and endocrine based tissue engineering projects, as well as cancer diagnosis screens.

      Anisotropic groove pattern of cell culture substratesTopographyMigration

Cells migrating on flat control surfaces and surfaces with topographically patterned ridges and grooves (north-south orientation)


Project III:
Non-viral transgene vectors are typically limited by short durations of expression.  In order to successfully transfect and differentiate enough cells in vivo for tissue engineering and gene therapy purposes, we need to maximize gene delivery and transgene expression in adult stem cells.  Part of the reason why non-viral plasmids have limited expression is that they fail to traffic to the nucleus, and then further into the appropriate subnuclear transcription centers.  My laboratory is aimed at understanding the dynamic behavior of non-viral vectors inside of cells, specifically within the nucleus.  We also study how extracellular biophysical cues influence intracellular plasmid movement in an attempt to modulate transgene expression for regenerative projects targeting neuronal and brown adipose tissues.

Expresssing and non-expressing plasmids in nuclei

Plasmids (green) traffic to subnuclear regions when actively being transcribed (left) compared to plasmids that are transcriptionally inactive (right)

GasiorowskiLabGasiorowskiLab2



Selected Publications (See Full PubMed results)

Evaluation of cystatin C as an early biomarker of cadmium nephrotoxicity in the rat.
Prozialeck WC, VanDreel A, Ackerman CD, Stock I, Papaeliou A, Yasmine C, Wilson K, Lamar PC, Sears VL, Gasiorowski JZ, DiNovo KM, Vaidya VS, Edwards JR.
Biometals. 2015 Dec 29.

Gradated assembly of multiple proteins into supramolecular nanomaterials.  
Hudalla GA, Sun T, Gasiorowski JZ, Han H, Tian YF, Chong AS, Collier JH
Nat Materials. 2014 Aug;13(8):829-36.

The influence of substrate topography on the migration of corneal epithelial wound borders.
Yanez-Soto B, Liliensiek SJ, Gasiorowski JZ, Murphy CJ, Nealey PF
Biomaterials. 2013 Dec;34(37):9244-51.

Biophysical cues and cell behavior: the big impact of little things.  
Gasiorowski JZ, Murphy CJ, Nealey PF
Annu Rev Biomed Eng. 2013;15:155-76.  

Early responses of vascular endothelial cells to topographic cues.
Dreier B, Gasiorowski JZ, Morgan JT, Nealey PF, Russell P, Murphy CJ
Am J Physiol Cell Physiol. 2013 Aug 1;305(3):C290-8.

Modulating adaptive immune responses to peptide self-assemblies.
Rudra JS, Sun T, Bird KC, Daniels MD, Gasiorowski JZ, Chong AS, Collier JH
ACS Nano. 2012 Feb 28;6(2):1557-64.

Directed intermixing in multicomponent self-assembling biomaterials.
Gasiorowski JZ, Collier JH
Biomacromolecules. 2011 Oct 10;12(10):3549-58.

Nonviral gene delivery.
Dean DA, Gasiorowski JZ
Cold Spring Harb Protoc. 2011 Mar 1

Alterations in gene expression of human vascular endothelial cells associated with nanotopographic cues.
Gasiorowski JZ, Liliensiek SJ, Russell P, Stephan DA, Nealey PF, Murphy CJ
Biomaterials. 2010 Dec;31(34):8882-8.

Multi-component extracellular matrices based on peptide self-assembly.
Collier JH, Rudra JS, Gasiorowski JZ, Jung JP.
Chem Soc Rev. 2010 Sep;39(9):3413-24.

Fibrillar peptide gels in biotechnology and biomedicine.
Jung JP, Gasiorowski JZ, Collier JH.
Biopolymers. 2010;94(1):49-59.

Biological properties of trabecular meshwork cells.
Gasiorowski JZ, Russell P
Exp Eye Res. 2009 Apr;88(4):671-5.

Response of human trabecular meshwork cells to topographic cues on the nanoscale level.  
Russell P, Gasiorowski JZ, Nealy PF, Murphy CJ
Invest Ophthalmol Vis Sci. 2008 Feb;49(2):629-35.

Intranuclear trafficking of episomal DNA is transcription-dependent.  
Gasiorowski JZ, Dean DA
Mol Ther. 2007 Dec;15(12):2132-9. 

Pol I transcription and pre-rRNA processing are coordinated in a transcription-dependent manner in mammalian cells.  
Kopp K*, Gasiorowski JZ*, Chen D, Gilmore R, Norton JT, Wang C, Leary DJ, Chan EK, Dean DA, Huang S.
Mol Biol Cell. 2007 Feb;18(2):394-403.

Postmitotic nuclear retention of episomal plasmids is altered by DNA labeling and detection methods.
Gasiorowski JZ, Dean DA
Mol Ther. 2005 Sep;12(3):460-7.

Hydroporation as the mechanism of hydrodynamic delivery.
Zhang G, Gao X, Song YK, Vollmer R, Stolz DB, Gasiorowski JZ, Dean DA, Liu D
Gene Ther. 2004 Apr;11(8):675-82.

Mechanisms of nuclear transport and interventions.
Gasiorowski JZ, Dean DA
Adv Drug Deliv Rev. 2003 Jun 16;55(6):703-16.