Biography

Dr. Holaska majored in biology at St. Joseph’s University and graduated in 1995. After working for one year at a molecular biology startup company (Recombinant BioCatalysis), he joined the graduate program in Microbiology (now Microbiology, Immunology and Cancer Biology) at the University of Virginia. Working under the guidance of Dr. Bryce Paschal he studied the molecular mechanisms for transport of molecules into and out of the nucleus. He received his Ph.D. in 2001. Dr. Holaska then trained in the laboratory of Dr Katherine Wilson at the Johns Hopkins School of Medicine for five years as a post-doctoral fellow. It is during this time that he became interested in understanding how nuclear structure and function impacted cellular function and cell-type specificity. His studies on the structure and function of the nuclear lamina made many important contributions to the field during this time. Dr. Holaska focused on emerin for his studies because emerin mutations cause muscle disease, thereby showing its importance in cellular function. During his time as a post-doctoral fellow he mapped the domain structure of emerin, showed that emerin bound multiple tissue-specific transcription regulators and inhibited their activity, developed a competitive model of protein binding to emerin that could explain tissue-specific gene regulation and found that emerin interacts with a proposed actin-based nucleoskeleton.

Dr. Holaska joined the Section of Cardiology in the Department of Medicine at the University of Chicago as an Assistant Professor in 2007. It was during this time Dr. Holaska became interested in understanding how emerin recruited or stabilized repressed genes at the nuclear periphery. Genomic organization is important for cell-type specificity to ensure genes to be activated are available for binding to transcription factors, while those to be repressed are unavailable to transcription factors. This is mediated by chromatin compaction and relaxation and by localization of chromatin to particular nuclear regions, including the nuclear lamina, which is repressive. The genome is also reorganized during stem cell differentiation to ensure the proper temporal expression of differentiation genes.

While at the University of Chicago, Dr. Holaska’s research program made many important discoveries. They found emerin was required for proper localization of repressed myogenic genes during myogenic differentiation. In the absence of emerin, myogenic differentiation is impaired due to the loss of the coordinated expression of myogenic differentiation genes; genes that are supposed to be at the nuclear periphery and repressed are now in the nuclear interior and activated. His research program also found emerin binds to a chromatin repressive enzyme, histone deacetylase 3 (HDAC3), and activates its activity. This provided a model for emerin regulation of chromatin repression at the nuclear periphery: emerin binding to HDAC3-bound chromatin activated HDAC3 to ensure repression of the genes in this area. Further, these interactions act as a scaffold to recruit other chromatin repressive complexes to further compact and repress these genomic regions.

Dr. Holaska returned back home to the Philadelphia region by accepting an Associate Professor position in the Department of Pharmaceutical Sciences at the University of the Sciences in 2014. Here he continued his research on the role of emerin in myogenic differentiation. His research program found emerin was required for myogenic differentiation because of its interaction with HDAC3. They found that increasing HDAC3 activity in the absence of emerin could rescue myogenic differentiation by rescuing the localization of repressed genes to the nuclear periphery during differentiation.  

In 2017, Dr. Holaska accepted an Associate Professor position in the Department of Biomedical Sciences at Cooper Medical School of Rowan University. His research program continues the work on emerin regulation of genomic reorganization during myogenic stem cell differentiation. They recently showed inhibiting histone acetyltransferases (HAT) also rescues emerin-null myogenic differentiation. HAT inhibition and HDAC3 activation have similar effects on chromatin, demonstrating that emerin regulation of chromatin architecture through control of histone acetylation plays a key role in stem cell differentiation. Dr. Holaska’s research program also started investigating how emerin regulation of nuclear structure impacts cancer cell metastasis. Cancer cells need to squeeze through incredibly small spaces during metastasis, for which the size of the nucleus is a major barrier. During metastatic transformation, nuclear structure changes so that it becomes more compliant and smaller in size. His research program recently found emerin is a key factor in for the nuclear structural changes occurring during transformation. Invasive breast cancer cells have reduced emerin expression, have decreased nuclear size, migrate faster, and more readily squeeze through tight spaces. Importantly, increasing emerin expression increased nuclear size and impaired migration. The mechanism(s) for how emerin regulates nuclear structure during cancer transformation will have a significant impact on metastasis. This work continues in Dr. Holaska’s lab. How emerin regulates genomic re-organization during stem cell differentiation is also an area of emphasis in his lab.

Current Students and Staff

Graduate Students

2015-present  Kimbre Nee, M.S.
Thesis: EDMD mutant myogenic progenitors have impaired differentiation

2016-present  Alexandra Liddane, Ph.D.
Thesis: Emerin regulation of nuclear structure in invasive breast cancer cells 

2016-present  Ashvin Iyer, Ph.D.
Thesis: The use of emerin-null and EDMD-causing emerin mutant myogenic progenitors to elucidate the EDMD mechanism

Undergraduate Students

2016-present  Katherine Bossone, University of the Sciences (accepted into PhD program at Johns Hopkins University)

2018-present  Hannah Smith, Rowan University

Lab Alumni

Postdoctoral Fellows

2009-2013       Megan Puckelwartz, Ph.D. (Co-sponsored)
Project: Analyzing muscle structure and function in Lmo7-null mice 

2010-2013       Eugene Wyatt, Ph.D. (Co-sponsored)
Project: Creating EDMD-causing emerin mutant myogenic progenitors

Graduate Students

2009-2010       Zinaida Dedeic, M.S.
Thesis: Emerin interaction with the transcriptional factor Lmo7 regulates myogenic differentiation. 

2009-2013       Adam Koch, Ph.D.
Thesis: Emerin and the regulation of genes at the nuclear envelope during myogenesis. 

2014-2015       Amethyst Fiorentino, M.S.
Project: Emerin binding to HDAC3 regulates myogenic transcription factors

Undergraduate Students

2009                Elizabeth Day, Purdue University (currently Research Specialist at the University of Illinois at Chicago)

2009-2011       Justin Demmerle, University of Chicago (currently in PhD program at Oxford University)

2011-2013       Lehka Nair, University of Chicago (currently in PhD program at Columbia University)

2011-2013       Jean Lee, University of Chicago

2014-2015       Judy Lam (currently in PharmD program)

2014-2015       Adellah Johnson (currently in graduate program at Long Island University)

2014-2017       Joseph Ellis, University of the Sciences (currently in PhD program at the University of Florida)

2015-2017       Shelby Woodson, University of the Sciences (currently a Manufacturing Associate I at WuXi AppTec) 

2015-2017       Lorraine Gorelick, University of the Sciences (currently at Coriell Institute)

2016-2017       Connor Quinn, University of the Sciences (currently in PhD program at Temple University)

2017-2018       Philip White, University of the Sciences (currently at start-up biotech company)