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Visit the Tesar Lab Website


Paul Tesar
Assistant Professor
Ph.D. Training Faculty
Department of Genetics
School of Medicine
Case Western Reserve University
Biomedical Research Building 721
2109 Adelbert Road
Cleveland, Ohio 44106-4955
Tel: (216) 368-6225
Fax: (216) 368-3432
E-mail: paul.tesar@case.edu


About Paul Tesar

Paul Tesar graduated with a B.S. in biology from Case Western Reserve University and went on to earn his Ph.D. from the University of Oxford as a recipient of the prestigious NIH-Oxford Biomedical Research Scholarship. He then continued his training as a postdoctoral fellow at the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. His graduate and postdoctoral studies, under the tutelage of Professor Sir Richard Gardner and Dr. Ron McKay, focused on understanding the molecular mechanisms and therapeutic potential of pluripotent stem cells which led to his discovery of epiblast stem cells (EpiSCs). Paul has received numerous scientific awards including the Harold M. Weintraub Award of the Fred Hutchinson Cancer Research Center and the Beddington Medal of the British Society for Developmental Biology.

Paul, a Cleveland native, returned home in 2009 and joined the Case Western Reserve School of Medicine as a faculty member in the Department of Genetics where he is continuing his studies on the use of both adult and embryonic stem cells to understand and treat human disease. Paul is a member of the Center for Stem Cell and Regenerative Medicine and serves as director of the Pluripotent Stem Cell Facility. He also maintains an adjunct appointment in the Department of Stem Cell Biology and Regenerative Medicine at the Lerner Research Institute of the Cleveland Clinic. In 2011, Paul was named a Robertson Investigator of the New York Stem Cell Foundation. One of only four awardees, the honor recognizes and supports scientists leading their generation in stem cell research.


Research

A longstanding and central question in biology is how a single cell, the fertilized egg, generates all the diverse cell types of the body. Our laboratory is primarily interested in the molecular mechanisms by which cells acquire specific identities during development and maintain those identities as adults. We use stem cells to understand mammalian development and associated diseases.

We focus on three general questions:

1. How do pluripotent cells (those that can become any cell type in the body) differentiate into specific cell fates?

  • Approach: We use mouse & human embryonic stem cells and mouse epiblast stem cells to interrogate the intrinsic and extrinsic signals that direct cells into specific fates.
  • Impact: Understanding of developmental signals provides insight into why perturbations cause disease. Additionally, these studies provide a mechanism to produce functional cell types for potential use in clinical therapies.
  • Current Projects:
    1. molecular and genetic understanding of mouse and human pluripotent stem cell states
    2. differentiation of pluripotent stem cells into functional neural fates
2. How do differentiated cell types maintain their identity?
  • Approach: We modify transcription factor programs to induce cells to switch fates.
  • Impact: Understanding the mechanisms underlying cellular identity allows for the prevention of revertant/aberrant cell fates (i.e. cancer). Additionally, these studies may allow for production of clinically useful cell types for therapy.
  • Current Projects:
    1. Reprogramming of adult cells into embryonic-like induced pluripotent stem cells (iPS cells)
    2. Reprogramming of non-neural cells directly into neural fates
3. What are the genetic and epigenetic mechanisms that contribute to developmental disorders?
  • Approach: We use induced pluripotent stem cells from human patients with neurodevelopmental disorders to study the cellular and molecular aberrations that contribute to disease.
  • Impact: Unlike other species, access to developing human tissues is not feasible. The iPS cell technology now allows access to pluripotent cells from individual patients. By comparing iPS cells from different patients, we have a tractable system to study human developmental genetics.
  • Current Projects:
    1. Use of iPS cells to compare neural development between control patients and patients with mental health disorders
    2. Use of iPS cells to compare neural development between control patients and patients with neurodevelopmental disorders


Selected Publications

Iwafuchi-Doi M, Matsuda K, Murakami K, Niwa H, Tesar PJ, Aruga J, Matsuo I, Kondoh H (2012)
Transcriptional regulatory networks in epiblast cells and during anterior neural plate development as modeled in epiblast stem cells.
Development;139(21):3926-37
See PubMed abstract

Nelson VR, Heaney JD, Tesar PJ, Davidson NO, Nadeau JH (2012)
Transgenerational epigenetic effects of the Apobec1 cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability.
Proc Natl Acad Sci U S A;109(41):E2766-73
See PubMed abstract

Song J, Saha S, Gokulrangan G, Tesar PJ, Ewing RM (2012)
DNA and chromatin modification networks distinguish stem cell pluripotent ground States.
Mol Cell Proteomics;11(10):1036-47
See PubMed abstract

Mallon BS, Chenoweth JG, Johnson KR, Hamilton RS, Tesar PJ, Yavatkar AS, Tyson LJ, Park K, Chen KG, Fann YC, McKay RD (2012)
StemCellDB: The Human Pluripotent Stem Cell Database at the National Institutes of Health.
Stem Cell Res;10(1):57-66
See PubMed abstract

De Los Angeles A, Loh YH, Tesar PJ, Daley GQ (2012)
Accessing naïve human pluripotency.
Curr Opin Genet Dev;22(3):272-82
See PubMed abstract

Akhtar-Zaidi B, Cowper-Sal-lari R, Corradin O, Saiakhova A, Bartels CF, Balasubramanian D, Myeroff L, Lutterbaugh J, Jarrar A, Kalady MF, Willis J, Moore JH, Tesar PJ, Laframboise T, Markowitz S, Lupien M, Scacheri PC (2012)
Epigenomic enhancer profiling defines a signature of colon cancer.
Science;336(6082):736-9
See PubMed abstract

Woo DH, Kim SK, Lim HJ, Heo J, Park HS, Kang GY, Kim SE, You HJ, Hoeppner DJ, Kim Y, Kwon H, Choi TH, Lee JH, Hong SH, Song KW, Ahn EK, Chenoweth JG, Tesar PJ, McKay RD, Kim JH (2012)
Direct and indirect contribution of human embryonic stem cell-derived hepatocyte-like cells to liver repair in mice.
Gastroenterology;142(3):602-11
See PubMed abstract

Miller RH, Tesar PJ (2011)
Tracking down the human myelinating cell.
Nat Biotechnol;29(10):881-3
See PubMed abstract

Hyun I, Tesar P (2011)
Stem cells: Cloning advance calls for careful regulation.
Nature;478(7367):36-7
See PubMed abstract

Najm FJ, Zaremba A, Caprariello AV, Nayak S, Freundt EC, Scacheri PC, Miller RH, Tesar PJ (2011)
Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells.
Nat Methods;:
See PubMed abstract

Zentner GE, Tesar PJ, Scacheri PC (2011)
Epigenetic signatures distinguish multiple classes of enhancers with distinct cellular functions.
Genome Res;:
See PubMed abstract

Najm FJ, Chenoweth JG, Anderson PD, Nadeau JH, Redline RW, McKay RD, Tesar PJ (2011)
Isolation of epiblast stem cells from preimplantation mouse embryos.
Cell Stem Cell;8(3):318-25
See PubMed abstract

Zentner GE, Hurd EA, Schnetz MP, Handoko L, Wang C, Wang Z, Wei C, Tesar PJ, Hatzoglou M, Martin DM, Scacheri PC (2010)
CHD7 functions in the nucleolus as a positive regulator of ribosomal RNA biogenesis.
Hum Mol Genet;19(18):3491-501
See PubMed abstract

Hemberger M, Udayashankar R, Tesar P, Moore H, Burton GJ (2010)
ELF5-enforced transcriptional networks define an epigenetically regulated trophoblast stem cell compartment in the human placenta.
Hum Mol Genet;:
See PubMed abstract

Chenoweth JG, McKay RD, Tesar PJ (2010)
Epiblast stem cells contribute new insight into pluripotency and gastrulation.
Dev Growth Differ;:
See PubMed abstract

Greber B, Wu G, Bernemann C, Joo JY, Han DW, Ko K, Tapia N, Sabour D, Sterneckert J, Tesar P, Schöler HR (2010)
Conserved and Divergent Roles of FGF Signaling in Mouse Epiblast Stem Cells and Human Embryonic Stem Cells.
Cell Stem Cell;6(3):215-226
See PubMed abstract

Chenoweth JG, Tesar PJ (2010)
Isolation and maintenance of mouse epiblast stem cells.
Methods Mol Biol;636:25-44
See PubMed abstract

Di Stefano B, Buecker C, Ungaro F, Prigione A, Chen HH, Welling M, Eijpe M, Mostoslavsky G, Tesar P, Adjaye J, Geijsen N, Broccoli V (2010)
An ES-like pluripotent state in FGF-dependent murine iPS cells.
PLoS One;5(12):e16092
See PubMed abstract

Schnetz MP, Handoko L, Akhtar-Zaidi B, Bartels CF, Pereira CF, Fisher AG, Adams DJ, Flicek P, Crawford GE, Laframboise T, Tesar P, Wei CL, Scacheri PC (2010)
CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression.
PLoS Genet;6(7):e1001023
See PubMed abstract

Anderson PD, Nelson VR, Tesar PJ, Nadeau JH (2009)
Genetic Factors on Mouse Chromosome 18 Affecting Susceptibility to Testicular Germ Cell Tumors and Permissiveness to Embryonic Stem Cell Derivation.
Cancer Res;:
See PubMed abstract

Chou YF, Chen HH, Eijpe M, Yabuuchi A, Chenoweth JG, Tesar P, Lu J, McKay RD, Geijsen N (2008)
The growth factor environment defines distinct pluripotent ground states in novel blastocyst-derived stem cells.
Cell;135(3):449-61
See PubMed abstract

Xi H, Shulha HP, Lin JM, Vales TR, Fu Y, Bodine DM, McKay RD, Chenoweth JG, Tesar PJ, Furey TS, Ren B, Weng Z, Crawford GE (2007)
Identification and characterization of cell type-specific and ubiquitous chromatin regulatory structures in the human genome.
PLoS Genet;3(8):e136
See PubMed abstract

Tesar PJ, Chenoweth JG, Brook FA, Davies TJ, Evans EP, Mack DL, Gardner RL, McKay RD (2007)
New cell lines from mouse epiblast share defining features with human embryonic stem cells.
Nature;448(7150):196-9
See PubMed abstract

Mackay DL, Tesar PJ, Liang LN, Haynesworth SE (2006)
Characterizing medullary and human mesenchymal stem cell-derived adipocytes.
J Cell Physiol;207(3):722-8
See PubMed abstract

Tesar PJ (2005)
Derivation of germ-line-competent embryonic stem cell lines from preblastocyst mouse embryos.
Proc Natl Acad Sci U S A;102(23):8239-44
See PubMed abstract