Department of Biological Sciences, Lehigh University

Research

DNA (‘the Blueprint of Life’) must be reproduced, interpreted and modified by cells to ensure survival. In simple terms, DNA interactions can be accomplished in two ways. One DNA molecule (a chromosome) can become tethered to another DNA molecule. A prime example occurs during DNA replication. Each chromosome is duplicated and the resulting sister chromatids (the products of chromosome replication) become tethered together. Evidence obtained by the Skibbens lab and others suggest that the process of tethering together sister chromatids is coordinated with DNA replication fork and occurs in proximity to other forms of DNA chromatinizations that include histone deposition and condensin recruitment (Images modified from Rudra and Skibbens 2013 J Cell Science).

Robert Skibbens, Ph.D.

A second type of DNA interaction occurs when a chromosome loops back on itself to stabilize the assembly of protein complexes at that intersection. An example here is transcription regulation – different sequences of DNA such as enhancers and promoters must come into registration to facilitate the assembly of protein complexes through which DNA is transcribed into RNA. Enhancers and promoters, however, often reside on a chromosome at large distances from one another. DNA looping allows these DNA sequences (E=Enhancer, P=Promoter) to come into close proximity with the base of these loops similarly tethered together by cohesins (Red). Note that looping is also critical for chromosome condensation, a process through which long, amorphous strands of DNA become compacted into discrete structures (Images modified from Skibbens 2015 Current Biology).

Robert Skibbens, Ph.D.

Cohesins are a complex of proteins that stabilize all sorts of DNA-DNA interactions including sister-sister chromatid tethering, enhance-promoter registration and even associations of non-identical DNA sequences across different chromosomes. As such, cohesins are essential for chromosome segregation, transcription regulation and DNA repair. Ctf7/Eco1 (and human homologs ESCO1 and ESCO2) is an essential regulator of cohesins of tremendous clinical Robert Skibbens, Ph.D. importance. For instance, mutations in ESCO family members are associated with aneuploidy (hallmark of cancer cells), cell death and severe developmental defects which likely arise through deregulation of transcription programs required for proper development (Image modified from Skibbens 2015 Current Biology).

The Skibbens Lab actively pursues all aspects of cohesin and ESCO-type protein functions. While we predominantly use yeast as a model system, collaborations with the Cassimeris and Iovine labs using human tissue culture cells and zebrafish fin regeneration, respectively providing exciting insights into defects that in humans lead to severe disease states including cancer and birth defects.

The Skibbens lab has received funding support from the Susan G. Komen Foundation and the National Science Foundation and is currently supported by the National Institutes of Health.

Publications

Research Publications | Reviews and Book Chapters

Research Publications

Mfarej MG, and Skibbens RV. (submitted). Genetically-induced Rodox Stress Occurs in a Yeast Model for Roberts Syndrome. G3.

Mfarej MG, and Skibbens RV. 2020. DNA damage induces Yap5-dependent transcription of ECO1/CTF7 in Saccharomyces cerevisiae. PLoS One. 15(12):e0242968. Click here for data file.

Zuilkoski CM, and Skibbens RV. 2020. PCNA antagonizes cohesin-dependent roles in genomic stability. PLoS One. 15(10):e0235103. Click here for data files.

Zuilkoski CM, and Skibbens RV. 2020. PCNA promotes context-specific sister chromatid cohesion establishment separate from that of chromatin condensation. Cell Cycle. 19(19):2436-2450. Click here for data files that underlie the results published in Zuilkoski/Skibbens 2020

Shen D, Skibbens RV. 2020. Promotion of Hyperthermic-Induced rDNA Hypercondensation in Saccharomyces cerevisiae. Genetics 214(3):589-604.

Shen, D., and Skibbens, RV. (2017) Chl1 DNA helicase and Scc2 function in chromosome condensation
through cohesin deposition. PLoS One 12(11):e0188739.

Click here for data files that underlie the results published in Shen/Skibbens 2017

Banerji R, Skibbens RV, Iovine MK. (2017) Cohesin mediates Esco2-dependent transcriptional regulation in a zebrafish regenerating fin model of Roberts Syndrome. Biol Open 6(12):1802-1813.

Shen, D-L., and Skibbens, R. V. (2017) Temperature-dependent regulation of rDNA condensation in Saccharomyces cerevisiae. Cell Cycle 20: 1-10.

Banerji, R., Eble, D., Iovine, M.K., Skibbens, RV (2016). Esco2 regulates cx43 expression during skeletal regeneration in the zebrafish fin. Dev Dyn. 2015 Oct 5. doi: 10.1002/dvdy.24354.

Tong, K. and Skibbens, RV (2015). Pds5 regulators segregate cohesion and condensation pathways in Saccharomyces cerevisiae. PNAS 112 (22); 7021-7026.

Tong, K. and Skibbens, RV (2014). Cohesin without Cohesion: A Novel Role for Pds5 in Saccharomyces cerevisiae. PLoS One 9 (6); e100470.

Rudra, S., Skibbens, RV (2013). Chl1 DNA Helicase Regulates Scc2 Deposition Specifically during DNA-Replicaation in Saccharomyces cerevisiae. PLoS One 8 (9): e75435.

Rudra, S. and Skibbens, R. V. (2012). Sister Chromatid cohesion establishment occurs in concert with lagging strand synthesis. Cell Cycle 11: 2114-2121.

Maradeo, M. E., Garg, A. and Skibbens, R. V. (2010). RFC small subunit regulation of sister chromatid pairing reactions in budding yeast. Cell Cycle 9 (21): 4370-4378.

Maradeo, M. E. and Skibbens, R. V. (2010). Replication factor C complexes play unique pro- and anti-establishment roles in sister chromatid cohesion. PLoS ONE 5 (10): e15381.

Maradeo, M. E. and Skibbens, R. V. (2010). Epitope tag-induced synthetic lethality between cohesin subunits and Ctf7/Eco1 acetylatransferase. FEBS Letters 584: 4037-4040.

Skibbens, R. V., Marzillier, J. and Eastman, L. 2010. Cohesins coordinate gene transcriptions of related function within Saccharomyces cerevisiae. Cell Cycle 9:8, 1601-1606.

Maradeo, M.E. and Skibbens, R.V. 2009. The Elg1-RFC clamp-loading complex performs a role in sister chromatid cohesion. PLoS ONE 4(3): e4707.

Skibbens, RV., Ringhoff, DN., Marzillier, J., Cassimeris, L., and Eastman, L. 2008. Positional Analyses of BRCA1-dependent Expression in Saccharomyces cerevisiae. Cell Cycle 7: 3928-3934.

Brands, A. and Skibbens, RV. 2008. Sister Chromatid Cohesion Role for CDC28-CDK in Saccharomyces cerevisiae. Genetics 180: 7-16.

Skibbens, R.V., Sie, C., and Eastman, L. 2008. Role of Chromosome Segregation Genes in BRCA1-dependent Lethality. Cell Cycle 7: 2071-2072.

Antoniacci, LM, Kenna, MA, and Skibbens, RV. 2007. The nuclear envelope and spindle pole body-associated Mps3 protein bind telomere regulators and function in telomere clustering. Cell Cycle 6: 75-79.

Milutinovich, M., Unal, E., Ward, C., Skibbens, RV. and Koshland, D. 2007. A multi-step pathway for the establishment of sister chromatid cohesion. PLoS Genet. 3: e12-e17.

Noble, D., Kenna, MA., Dix, M., Skibbens, RV., Unal, E. and Guacci, V. 2006. Intersection between the regulators of sister chromatid cohesion establishment and maintenance in budding yeast indicate a multi-step mechanism. Cell Cycle 5: 2528-2536.

Antoniacci, L.M. and R. V. Skibbens. 2006. Sister-chromatid cohesion is non-redundant and resists both spindle forces and telomere motility. Current Biology 16: 902-906.

Brands, A. and Skibbens, R. V. 2005. Ctf7p/Eco1p exhibits acetyltransferase activity – but does it matter? Current Biology 15: R50-51.

Antoniacci, L. M., Kenna, M. A., Uetz, P., Fields, S., and Skibbens, R. V. 2004.The spindle pole body assembly component Mps3p/Nep98p functions in sister chromatid cohesion. J. Biol. Chem. 279: 49542-49550.

Skibbens, R.V. 2004. Chl1p, a DNA helicase-like protein in budding yeast, functions in sister chromatid cohesion. Genetics 166: 33-42.

Bellows, A.M., Kenna, M.A., Cassimeris, L., and Skibbens, R.V. 2003. Human EFO1p exhibits acetyltransferase activity and is a unique combination of linker histone and Ctf7p/Eco1p chromatid cohesion establishment domains. Nucleic Acids Research. 31: 6334-6343.

Kenna, M. and Skibbens, R.V. 2003. Mechanical Link between Cohesion Establishment and DNA Replication: Ctf7p/Eco1p, a Cohesion Establishment Factor, Associates with Three Different Replication Factor C Complexes. Mol. Cell. Biol. 23: 2999-3007.

Skibbens, R. V., L. B. Corson, D. Koshland and P. Hieter. 1999. Ctf7p is essential for sister chromatid cohesion and links mitotic chromosome structure to the DNA replication machinery. Genes & Development 13(3):307-319.

Shaw, S. L., P. Maddox, R. V. Skibbens, E. Yeh, E. D. Salmon and K. Bloom. 1998. Nuclear and spindle dynamics in budding yeast. Mol. Biol. Cell 9(7): 1627-1631.

Skibbens, R. V. and E. D. Salmon. 1997. Micromanipulation of chromosomes in mitotic newt cells: tension controls the state of kinetochore movement. Exp. Cell Research 235(2):314-324.

Waters, J. C., R. V. Skibbens and E. D. Salmon. 1996. Oscillating mitotic newt lung cell kinetochores are, on average, under tension and rarely push. J. Cell Science 109:2823-2831.

Yeh, E., R. V. Skibbens, J. W. Cheng, E. D. Salmon, and K. Bloom. 1995. Spindle dynamics and cell cycle regulation of dynein in the budding yeast, Saccharomyces cerevisiae. J. Cell Biol. 130(3): 687-700.

Skibbens, R. V., C. L. Rieder, and E. D. Salmon. 1995. Kinetochore motility after severing between sister centromere using laser microsurgery: Evidence that kinetochore directional instability and position are regulated by tension. J. Cell Science 108(7):2537-2548.

Skibbens, R. V., V. P. Skeen and E. D. Salmon. 1993. Directional instability of kinetochore motility during chromosome congression and segregation in mitotic newt lung cells: a push-pull mechanism. J. Cell Biol. 122(4):859-875.

Gliksman, N. R., R. V. Skibbens, and E. D. Salmon. 1993. How the transition frequencies of microtubule dynamic instability (nucleation, catastrophe, and rescue) regulate microtubule dynamics in interphase and mitosis: Analysis using a Monte Carlo computer simulation. Mol. Biol. Cell 4:1035-1050.

Yeh, G., H. Marsh, G. Carson, M. Concino, S. Scesney, R. Kuestner, R. Skibbens, K. Donahue, L. Berman, and S. Ip. 1991. Recombinant soluble human complement receptor Type 1 inhibits inflammation in the reversed passive Arthus reaction in rats. J. Immun. 146:250-256.

Hertzberg, E. L. and R. V. Skibbens. 1984. A protein homologous to the 27,00 Dalton liver gap junction protein is present in a wide variety of species and tissues. Cell 39:61-69.

top

Reviews and Book Chapters

Mfarej MG, and Skibbens RV. 2020. An ever-changing landscape in Roberts syndrome biology: Implications for macromolecular damage. PLoS Genetics. 16(12):e1009219.

Skibbens RV. (2019) Condensins and cohesins - one of these things is not like the other! J Cell Science 132(3). pii: jcs220491.

Banerji R, Skibbens RV, Iovine MK. How many roads lead to cohesinopathies? Dev Dyn. 2017 Apr 19.

Skibbens, R. V. (2016) Of Rings and Rods: Reguating Cohesin Entrapment of DNA to Generate Intra- and Intermolecular Tethers. PLoS Genetics 12(12): e1006478. Corrected version

Skibbens, RV (2015). Cell Biology: Cohesin Rings Leave Loose Ends. Current Biology 25 (3) R108.

Skibbens, RV, Colquhoun, JM, Green, MJ, Molnar, CA, Sin, DN, Sullivan, BJ, Tanzosh, EE (2013). Cohesinopathies of a Feather Flock Together. PLoS Genetics 9 (12); e1004036.

Rudra, S., and Skibbens, R. V. (2013). Cohesin codes - interpreting chromatin architecture and the many facets of cohesin function. Journal of Cell Science 126, 31-41.

Skibbens, R. V. (2011). Sticking a fork in cohesin - it's not done yet! Trends in Genetics 27(12): 487-526.

Skibbens, R. V. (2010). Buck the establishment: re-inventing sister chromatid cohesion. Trends in Cell Biology 20: 507-513.

Skibbens, R. V. (2010). A sliding scale: The many faces of Ctf7Eco1 cohesion establishment factor in DNA repair. Cell Cycle.

Skibbens, RV. 2009. Establishment of Sister Chromatid Cohesion. Current Biology 19: R1126-R1132.

Skibbens, RV. 2008. Mechanisms of Sister Chromatid Pairing. International Review of Cell and Molecular Biology 269: 283-339.

Skibbens, RV. 2008. Cell biology of cancer: BRCA1 and sister chromatid pairing reactions? Cell Cycle 7: 449-452.

Skibbens, R.V., Maradeo, M., and Eastman, L. 2007. Fork it over: the cohesion establishment factor Ctf7p and DNA replication. J. Cell Sciences 120: 2471-2477.

Skibbens, R. V. 2005. Unzipped and Loaded: The role of DNA helicases and RFC clamp-loading complexes in sister chromatid cohesion. Journal of Cell Biology 169: 841-846.

Cassimeris, L., and Skibbens, R.V. 2003. Regulated assembly of the mitotic spindle: A perspective from two ends. Current Issues in Molecular Biology 5: 99-112.

Skibbens, R. V. 2000. Holding your own: Establishing sister chromatid cohesion. Genome Research. Vol. 10:1664-71.

Salmon, E.D., Yeh, E., Shaw, S., Skibbens, R.V., and Bloom, K. 1998. High-resolution video and digital-enhanced differential interference contrast light microscopy of cell division in budding yeast. Methods in Enzymology 298: 317-331.

Skibbens, R. V. and P. Hieter. 1998. Kinetochores and the checkpoint mechanism that monitors for defects in the chromosome segregation machinery. Ann. Rev. Genetics, Vol. 32, 307-337.

Bassett, D. E., M. Basrai, C. Connely, K. Hyland, K. Kitagawa, M. Mayer, D. Morrow, A. Page, V. Resto, R. V. Skibbens and P. Hieter. 1996. Exploiting the complete yeast genome sequence. Curr. Opin. Genet. Dev. 6(6):763-766.

Skibbens, R.V. and Salmon, E.D. 1994. Kinetochore directional instability in vertebrate mitotic cells. In NATO ASI Series Biomechanics of active movement and division of cells, Ed. Nuri Akkas, Springer-Verlag, Berlin. 545-550.

Skibbens, R. V. and E. D. Salmon. 1994. Kinetochore directional instability in vertebrate mitotic cells. In NATO ASI Series Biomechanics of active movement and division of cells, Ed. Nuri Akkas, Springer-Verlag, Berlin. 545-550.

Salmon, E. D., S. Magers, R. Skibbens, and N. Gliksman. 1991. Video-enhanced differential interference contrast (VE-DIC) light microscopy: A method for semi-automatic object tracking. Ed. G. W. Bailey, Proceedings of the 49th Annual Meeting of the Electron Microscopy Society of America, pg. 238.

top

Biographical Information

Education and Professional Preparation

Carnegie Institute of Washington, Baltimore, MD (8/97 to 8/99)
Department of Embryology
Post-doctoral Fellow with Dr. Doug Koshland (*&)
Topic: Chromosome cohesion and condensation

*Howard Hughes Medical Institute Investigator
&National Academy of Science

Johns Hopkins School of Medicine, Baltimore MD (3/95 to 8/97)
Department of Molecular Biology and Genetics
Post-doctoral Fellow with Dr. Phil Hieter (*&)
Topic: Genome stability and cell division

*Howard Hughes International Scholar
&Royal Society of Canada

University of North Carolina at Chapel Hill, NC (8/89 to 11/94)
Department of Biology
Ph.D. Thesis with Dr. E. D. Salmon (*)
Topic: Mechnaics of spindle force production

*James Larkin Iona Mae Ballou Distinguished Professor

Ohio State University, Columbus, OH (8/77 to 6/81)
Bachelor of Science: Zoology, 1991

Employment

Lehigh University, Bethlehem, PA (9/99 to present)
Department of Biological Sciences
Topic: Development and Cancer, Cell Cycle
Professor (5/12 to present)
Associate Professor (6/05 to 5/12)
Assistant Professor (9/99 to 5/05)

T Cell Sciences, Inc., Cambridge, MA (9/86 to 8/89)
Scientist
Topics: Human immune system activation/suppresion

Baylor College of Medicine, Houston, TX (2/82 to 8/86)
Department of Biochemistry
Research Assistant
Topic: Cell communication mechanisms

Honors and Awards

U.S. Patent #90901370.8 (9/27/90)
Monoclonal antibodies reactive with defined regions of the T Cell Antigen Receptor. Patent Holder: T Cell Sciences, Inc. Inventor: R. V. Skibbens et al.

European Patent #98106540.2-2116 (7/28/98)
Monoclonal antibodies reactive with defined regions of the T Cell Antigen Receptor. Patent Holder: T Cell Sciences, Inventor: R.V. Skibbens et al.

Research Funding

Current Awards
Competitively awarded research grants

National Institute of General Medicine Sciences Grant, 2014-2017
Department of Health and Human Services
Principal Investigator: Robert V. Skibbens
"DNA helicase functions in genome maintenance"
Award No. 1R15GM110631-01

Completed Awards
Competitively awarded research grants

National Institute of General Medical Sciences Grant, 2011-2014
Department of Health and Human Services
Principal Investigator – Robert V. Skibbens
“Mechanisms of sister chromatid pairing”
Award No. 1R15GM083269-02

Faculty Innovation Grants (FIG) – Lehigh University (2011-2012)
Principal Investigator – Robert V. Skibbens
“Developing a vertebrate model system for studying and treating SC
Phocomelia/Roberts Syndrome and Cornelia de Lange Syndrome”
* FIG led to collaboration with Iovine lab (manuscript under review)

Pennsylvania Department of Health – PA
Health Research Formula Fund award, 2009-2011
RFA #05-07-10; SAP # 4100047638
Co-Principal Investigator: Robert Skibbens (Lynne Cassimeris – PI)
“Targeted killing of cancer cells”

Susan G. Komen for the Cure Research Grant, 2007-2010
Basic, Clinical and Translational Research - Division of Tumor Cell Biology
Principal Investigator – Robert V. Skibbens
“Cohesion-dependent Mechanisms of Cancer Progression and Aneuploidy”
Award No. BCTR0707708

National Institute of General Medical Sciences Grant, 2008-2010
Department of Health and Human Services
Principal Investigator – Robert V. Skibbens
“Mechanisms of sister chromatid pairing”
Award No. 1R15GM083269-01

National Sciences Foundation Research Grant, 2002-2005
Division of Eukaryotic Genetics
Principal Investigator – Robert V. Skibbens
“Mechanisms of Sister Chromatid Pairing”
Award No. MCB-0212323

National Sciences Foundation REU Research Grant, 2003
Division of Eukaryotic Genetics
Principal Investigator – Robert V. Skibbens
Award No. MCB-0331898

National Science Foundation Equipment and Instrumentation Grant, 2002
Co-Principal Investigator – (Lynne Cassimeris – PI)
Contributed to proposal for Laser Scanning Confocal Microscope facility
Award No. DBI-0200322

State of Pennsylvania Health Research Initiative, 2004
Co-investigators – Drs. Robert V. Skibbens and Lynne Cassimeris
Award No. ME03-168

State of Pennsylvania Health Research Initiative, 2003
Co-investigators - Drs. Lynne Cassimeris and Robert V. Skibbens
Award No. ME02-162

National Institute for Health Research Grant, 1995-1998
NRSA Fellow – Robert V. Skibbens
Award No. 1F32GM017770

Teaching and Research Advising

Undergraduate Level Courses

BIOS 10/90 - BioScience in the 21st Century - Prof. Vassie Ware, Course Instructor
Fall 09, 10, 11, 14, 15 Selected lectures

BIOS 31 - Core I: Introduction to Cell and Molecular Biology
Spring 02, 03 with 136 and 164 students, respectively

BIOS 32 - Core I Lab: Introduction to Cell and Molecular Biology Lab
Spring 02, 03 with 9 sections/126 students and 10 sections/158 students,respectively)

BIOS 41 - Core I: Cell and Molecular Biology - Prof. Lynne Cassimeris - Instructor
Spring 12, 13, Guest lecturer

BIOS 90 - Science in Science Fiction – Freshman Seminar Series
Fall 04

BIOS 161 - Undergraduate Research – Independent topics
Spring 02

BIOS 225 - Junior Writing Intensive Certificate, Special Topics
Spring 00 (Aneuploidy and Cancer mechanisms)
Spring 01 (Checkpoints and Cancer),
Spring 02 (X-inactivation in higher eucaryotes)
Fall 02 (Acetylation and Transcription Regulation),
Spring 04 (Phosphatases and Cell Cycle Regulation)
Spring 08 (Sister chromatid pairing)

BIOS 261 - Topics in Cell Biology - Writing Intensive
Fall 09 (Aging and DNA Repair)

BIOS 328 - Immunology
Spring 04, 05, 08, 09, 10, 11, 12, 14

BIOS 367 - Cell Biology
Fall 08, 11

BIOS 388 - Honors Symposia
Guest lecture

BIOS 389 - Honors Project
Spring 02

BIOS 391 - Undergraduate Research
Fall 02, 03, 04; Spring 04

BIOS 396 - Special Topics in Cell Biology - cross-listed with BIOS 431 or 432
Fall 02 (Microscopy and Cell Imaging)
Fall 03 (Cell Cycle Control)
Spring 09 (Cancer Cell Biology)

Graduate Level Courses

BIOS 405 - Special Topics in Molecular Biology
Summer 02

BIOS 407 - Masters Thesis Research in Biological Sciences
Summer 02, 09, 11; Fall 05, 06, 07, 08, 09, 10, 11, 12; Spring 05, 06, 07 08, 09, 10

BIOS 411 - Program Core: Advanced Cell Biology
Fall 05, 06, 07, 08, 09, 10, 11, 12, 14

BIOS 421 - Program Core: Advanced topics in Molecular and Cell Biology
Spring 06 (Chromatin Remodeling and DNA Metabolism)
Spring 09 (Cancer Cell Biology)
Spring 10, 11, 14 (Molecular and Cellular Biology)

BIOS 431 - Advanced topics in Cell Biology
Fall 00 (Cell cycle control and mitotic checkpoints)
Fall 02 (Light and Electron Microscopy and Cell Imaging)
Fall 03 (Cell Cycle Control)
Spring 09* (Cancer Cell Biology)

BIOS 432 - Advanced Topics in Molecular Genetics
Fall 01 (Gene Silencing and Chromatin Remodeling)
Fall 03 (Cell Cycle Control)

BIOS 496 - Advanced topics in Cell Cycle and Division
Spring 13

BIOS 498 - Cell and Molecular Basis of Human Diseases
Spring 14

Distance Education

BIOS 407 - Masters Thesis – PhD Research Proposal
Fall 09, 10, 11, 12, 15
Spring 09, 10, 11, 12

BIOS 411 - Advanced Topics in Cell Biology
Fall 09, 10, 11, 12, 14

BIOS 421 - Molecular Cell Biology I
Spring 10, 11, 14