Timothy Hallstrom
,
Credentials
PhD
Credentials
PhD
Associate Professor, Department of Pediatrics
Faculty Member, Division of Pediatric Blood and Marrow Transplantation & Cellular Therapy
Research Scientist, Pediatric Blood and Marrow Transplant (BMT) Center
Faculty, Microbiology, Immunology and Cancer Biology (MICaB) Ph.D. Graduate Program
Faculty Member, Brain Tumor Program
Faculty, PhD Program in Molecular, Cellular, Developmental Biology and Genetics
Faculty, Masters Program in Stem Cell Biology
Biography
Bio
Dr. Hallstrom received his PhD in Molecular Biology at the University of Iowa in 1999. He then did post-doctoral studies with Joseph Nevins at Duke University studying the control of Rb/E2F induction of proliferation and apoptosis. He joined the University of Minnesota in 2007 as an Assistant Professor in the Department of Pediatrics Hematology and Oncology division.
Research Summary
Immune Response in Pediatric Retinoblastoma Tumors
Our research interests focus on two major areas. The first is on the pediatric cancer retinoblastoma, which forms in the retina of children and infants. This cancer is caused by deregulation of the Rb/E2F pathway. We developed a novel mouse retinoblastoma model that develops rapid bilateral tumors in both eyes. Recently, we learned that these tumors express a gene expression "signature" that causes recruitment and accumulation of immune cells to these tumors. Since this is a highly sought after clinical goal, we are elucidating the mechanisms of immune cell recruitment so they can be targeted to kill cancer cells.
Epigenetics of Retinal Development
The second major research interest is in the epigenetic control mechanisms responsible for normal retinal development. These mechanisms can malfunction in pediatric retinoblastoma, and may be harnessed during retinal regeneration to produce new retinal cell types after they've been lost. In particular, we study the retinal function of an epigenetic regulator called UHRF2, which binds to a DNA epigenetic base called 5-hydroxymethylcytosine (5hmC). It is still poorly understood how 5hmC accumulates during retinal development and how this leads to proper retinal gene expression. Furthermore, 5hmC is widely lost in human tumors, including retinoblastoma, although the mechanism behind its loss is unclear, as is the anti-tumor effectiveness of restoring 5hmC. We utilize genome-wide approaches to understand the altered gene expression and 5hmC distribution in retinal cells lacking the Uhrf2 gene.
Education
PhD in Molecular Biology,
University of Iowa, Iowa City, IA
Fellowships, Residencies, and Visiting Engagements
Postdoctoral Fellowship,
Duke University
Durham, North Carolina, United States
Honors and Recognition
Robert M. and Barbara R. Bell Award recipient, Duke Comprehensive Cancer Center for exceptional abilities in basic or translational research in areas relating to the diagnosis, cause, prevention or treatment of cancer, NC
Basic Science Paper of the Year (Associate or Full Professor), Department of Pediatrics, University of Minnesota (2023)
Elected Member, Society for Pediatric Research
Selected Publications
Selected Publications
Sarver, A. L., Xie, C., Riddle, M. J., Forster, C. L., Wang, X., Lu, H., Wagner, W., Tolar, J., Hallstrom, T. C.,
2021.
Retinoblastoma tumor cell proliferation is negatively associated with an immune gene expression signature and increased immune cells..
Laboratory investigation; a journal of technical methods and pathology,
101
(6):
701-718.
doi: https://doi.org/10.1038/s41374-021-00573-x
PubMed ID: 33658609.
Xie, C., Freeman, M. J., Lu, H., Wang, X., Forster, C. L., Sarver, A. L., Hallstrom, T. C.,
2017.
Retinoblastoma cells activate the AKT pathway and are vulnerable to the PI3K/mTOR inhibitor NVP-BEZ235..
Oncotarget,
8
(24):
38084-38098.
doi: https://doi.org/10.18632/oncotarget.16970
PubMed ID: 28445155.
Lu, H., Bhoopatiraju, S., Wang, H., Schmitz, N. P., Wang, X., Freeman, M. J., Forster, C. L., Verneris, M. R., Linden, M. A., Hallstrom, T. C.,
2016.
Loss of UHRF2 expression is associated with human neoplasia, promoter hypermethylation, decreased 5-hydroxymethylcytosine, and high proliferative activity..
Oncotarget,
7
(46):
76047-76061.
doi: https://doi.org/10.18632/oncotarget.12583
PubMed ID: 27738314.
Filtz, E. A., Emery, A., Lu, H., Forster, C. L., Karasch, C., Hallstrom, T. C.,
2015.
Rb1 and Pten Co-Deletion in Osteoblast Precursor Cells Causes Rapid Lipoma Formation in Mice..
PloS one,
10
(8):
e0136729.
doi: https://doi.org/10.1371/journal.pone.0136729
PubMed ID: 26317218.
Xie, C., Lu, H., Nomura, A., Hanse, E. A., Forster, C. L., Parker, J. B., Linden, M. A., Karasch, C., Hallstrom, T. C.,
2015.
Co-deleting Pten with Rb in retinal progenitor cells in mice results in fully penetrant bilateral retinoblastomas..
Molecular cancer,
14
93.
doi: https://doi.org/10.1186/s12943-015-0360-y
PubMed ID: 25907958.
Lu, H., Hallstrom, T. C.,
2013.
The nuclear protein UHRF2 is a direct target of the transcription factor E2F1 in the induction of apoptosis..
The Journal of biological chemistry,
288
(33):
23833-43.
doi: https://doi.org/10.1074/jbc.M112.447276
PubMed ID: 23833190.
Lu, H., Hallstrom, T. C.,
2012.
Sensitivity to TOP2 targeting chemotherapeutics is regulated by Oct1 and FILIP1L..
PloS one,
7
(8):
e42921.
doi: https://doi.org/10.1371/journal.pone.0042921
PubMed ID: 22900064.
Lu, H., Liang, X., Issaenko, O. A., Hallstrom, T. C.,
2011.
Jab1/CSN5 mediates E2F dependent expression of mitotic and apoptotic but not DNA replication targets..
Cell cycle (Georgetown, Tex.),
10
(19):
3317-26.
doi: https://doi.org/10.4161/cc.10.19.17618
PubMed ID: 21937878.
Bohrer, L. R., Chen, S., Hallstrom, T. C., Huang, H.,
2010.
Androgens suppress EZH2 expression via retinoblastoma (RB) and p130-dependent pathways: a potential mechanism of androgen-refractory progression of prostate cancer..
Endocrinology,
151
(11):
5136-45.
doi: https://doi.org/10.1210/en.2010-0436
PubMed ID: 20881251.
Hallstrom, T. C., Nevins, J. R.,
2009.
Balancing the decision of cell proliferation and cell fate..
Cell cycle (Georgetown, Tex.),
8
(4):
532-5.
doi: https://doi.org/10.4161/cc.8.4.7609
PubMed ID: 19182518.
Hallstrom, T. C., Mori, S., Nevins, J. R.,
2008.
An E2F1-dependent gene expression program that determines the balance between proliferation and cell death..
Cancer cell,
13
(1):
11-22.
doi: https://doi.org/10.1016/j.ccr.2007.11.031
PubMed ID: 18167336.
Hallstrom, T. C., Nevins, J. R.,
2006.
Jab1 is a specificity factor for E2F1-induced apoptosis..
Genes & development,
20
(5):
613-23.
doi: https://doi.org/10.1101/gad.1345006
PubMed ID: 16481464.
Black, E., Hallstrom, T., Dressman, H., West, M., Nevins, J.,
2005.
Distinctions in the Specificity of E2F Function Revealed by Gene Expression Signatures.
proc Natl Acad Sci U S A,
Zhang, X., Kolaczkowska, A., Devaux, F., Panwar, S. L., Hallstrom, T. C., Jacq, C., Moye-Rowley, W. S.,
2005.
Transcriptional regulation by Lge1p requires a function independent of its role in histone H2B ubiquitination..
The Journal of biological chemistry,
280
(4):
2759-70.
doi: https://doi.org/10.1074/jbc.M408333200
PubMed ID: 15528187.
Hallstrom, T. C., Nevins, J. R.,
2003.
Specificity in the activation and control of transcription factor E2F-dependent apoptosis..
Proceedings of the National Academy of Sciences of the United States of America,
100
(19):
10848-53.
doi: https://doi.org/10.1073/pnas.1831408100
PubMed ID: 12954980.
Giangrande, P. H., Hallstrom, T. C., Tunyaplin, C., Calame, K., Nevins, J. R.,
2003.
Identification of E-box factor TFE3 as a functional partner for the E2F3 transcription factor..
Molecular and cellular biology,
23
(11):
3707-20.
doi: https://doi.org/10.1128/MCB.23.11.3707-3720.2003
PubMed ID: 12748276.
Hallstrom, T. C., Lambert, L., Schorling, S., Balzi, E., Goffeau, A., Moye-Rowley, W. S.,
2001.
Coordinate control of sphingolipid biosynthesis and multidrug resistance in Saccharomyces cerevisiae..
The Journal of biological chemistry,
276
(26):
23674-80.
doi: https://doi.org/10.1074/jbc.M101568200
PubMed ID: 11323424.
Hallstrom, T. C., Moye-Rowley, W. S.,
2000.
Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae..
The Journal of biological chemistry,
275
(48):
37347-56.
doi: https://doi.org/10.1074/jbc.M007338200
PubMed ID: 10980204.
Hallstrom, T. C., Moye-Rowley, W. S.,
2000.
Hyperactive forms of the Pdr1p transcription factor fail to respond to positive regulation by the hsp70 protein Pdr13p..
Molecular microbiology,
36
(2):
402-13.
doi: https://doi.org/10.1046/j.1365-2958.2000.01858.x
PubMed ID: 10792726.
Hallstrom, T. C., Katzmann, D. J., Torres, R. J., Sharp, W. J., Moye-Rowley, W. S.,
1998.
Regulation of transcription factor Pdr1p function by an Hsp70 protein in Saccharomyces cerevisiae..
Molecular and cellular biology,
18
(3):
1147-55.
doi: https://doi.org/10.1128/MCB.18.3.1147
PubMed ID: 9488429.
Hallstrom, T. C., Moye-Rowley, W. S.,
1998.
Divergent transcriptional control of multidrug resistance genes in Saccharomyces cerevisiae..
The Journal of biological chemistry,
273
(4):
2098-104.
doi: https://doi.org/10.1074/jbc.273.4.2098
PubMed ID: 9442049.
Katzmann, D. J., Hallstrom, T. C., Mahé, Y., Moye-Rowley, W. S.,
1996.
Multiple Pdr1p/Pdr3p binding sites are essential for normal expression of the ATP binding cassette transporter protein-encoding gene PDR5..
The Journal of biological chemistry,
271
(38):
23049-54.
doi: https://doi.org/10.1074/jbc.271.38.23049
PubMed ID: 8798494.
Wu, A. L., Hallstrom, T. C., Moye-Rowley, W. S.,
1996.
ROD1, a novel gene conferring multiple resistance phenotypes in Saccharomyces cerevisiae..
The Journal of biological chemistry,
271
(6):
2914-20.
doi: https://doi.org/10.1074/jbc.271.6.2914
PubMed ID: 8621680.
Katzmann, D. J., Hallstrom, T. C., Voet, M., Wysock, W., Golin, J., Volckaert, G., Moye-Rowley, W. S.,
1995.
Expression of an ATP-binding cassette transporter-encoding gene (YOR1) is required for oligomycin resistance in Saccharomyces cerevisiae..
Molecular and cellular biology,
15
(12):
6875-83.
doi: https://doi.org/10.1128/MCB.15.12.6875
PubMed ID: 8524254.
Sigmund, C., TC, H., Yang, G., Merrill, D., Sinclair, N., Lang, J., Robillard, J.,
1994.
Expression of the human angiotensinogen (HUANG) gene in transgenic mice..
Wang, X., Sarver, A., Lu, H., Seiler, C., Xie, C., Forster, C., Tretyakova, N., Hallstrom, T.,
UHRF2 controls TET expression and 5hmC accumulation during retinal cell differentiation.
Selected Presentations
Selected Presentations
Hallstrom, T. C., (Author & Presenter)
"The 5hmC-binding protein UHRF2 is lost in retinoblastoma and is required for 5hmC accumulation, growth arrest, and differentiation of retinal progenitor cells",
Fifth International Rb Meeting,
Charleston,
South Carolina,
United States.
September 29, 2019.
Hallstrom, T. C., (Author & Presenter)
"UHRF2 control of 5hmC homeostasis and differentiation in retinal progenitor cells",
Neuro-oncology Symposium,
University of Minnesota,
Minneapolis,
Minnesota,
United States.
May 01, 2018.
Lu, H., (Author & Presenter), Hallstrom, T. C., (Author & Presenter)
"UHRF2 control of 5hmC homeostasis and differentiation in retinal progenitor cells Platform & Poster presentation",
Keystone Epigenetics Symposium,
Breckenridge,
Colorado,
United States.
February 10, 2018.
Hallstrom, T. C., (Author & Presenter)
"UHRF2 control of 5hmC homeostasis and differentiation in retinal progenitor cells",
Keystone Epigenetics Symposium,
Breckenridge,
Colorado,
United States.
February 10, 2018.
Hallstrom, T. C., (Author & Presenter)
"Epigenetics at the proliferation/differentiation switch in retinal progenitor cells",
Epigenetics Consortium,
University of Minnesota,
Minneapolis,
Minnesota,
United States.
July 01, 2017.
Lu, H., (Author & Presenter), Hallstrom, T. C., (Author & Presenter)
"Incipient retinoblastoma cells trigger a gene expression program for immune cell recruitment",
Fourth International Rb Meeting,
Columbus,
Ohio,
United States.
September 25, 2016.
Hallstrom, T. C., (Author & Presenter)
"Incipient retinoblastoma cells trigger a gene expression program for immune cell recruitment",
Fourth International Rb Meeting,
Columbus,
Ohio,
United States.
September 25, 2016.
Hallstrom, T. C., (Author & Presenter)
"Cell fate control by integrated E2F, FOXO, and AKT signing in retinal progenitor cells and retinoblastoma",
Grand Rounds,
Department of Pathology, University of North Carolina Lineberger Comprehensive Cancer Center,
Chapel Hill,
North Carolina,
United States.
May 25, 2016.
Hallstrom, T. C., (Author & Presenter)
"Cell fate control by integrated E2F, FOXO, and AKT signing in retinal progenitor cells and retinoblastoma",
Department of Tumor Biology, H. Lee Moffitt Cancer Center,
Tampa,
Florida,
United States.
February 23, 2016.
Hallstrom, T. C., (Author & Presenter)
"Rb/E2F and Pten/Akt signaling pathways converge to control retinoblastoma emergence",
University of Colorado - Denver,
Denver,
Colorado,
United States.
May 18, 2015.
Hallstrom, T. C., (Author & Presenter)
"Novel Pathways in Pediatric Retinoblastoma and Implications for Therapy",
Pediatric Grand Rounds,
University of Minnesota,
Minneapolis,
Minnesota,
United States.
February 01, 2015.
Hallstrom, T. C., (Author & Presenter)
"The Rb/E2F and Akt/FoxO pathways intersect to distinguish "oncogenic" from "genuine" proliferative cues in retinoblastoma",
Science Park of the University of Texas M.D. Anderson Cancer Center,
Smithville,
Texas,
United States.
February 12, 2014.
Hallstrom, T. C., (Author & Presenter)
"Cell fate control by integrated E2F, FoxO and P13K signaling in retinoblastoma",
Third International Rb Meeting,
Monterey,
California,
United States.
October 07, 2013.
Hallstrom, T. C., (Author & Presenter)
"Rb-E2f1 & Akt: How do cells distinguish 'normal' growth from oncogenic stimulation?",
MCDB&G presentation to incoming graduate students,
Itasca,
Minnesota,
United States.
August 01, 2013.
Hallstrom, T. C., (Author & Presenter)
"Rb/E2F1 & Akt: How do cells distinguish 'normal' growth from oncogenic stimulation?",
MCDB&G presentation,
University of Minnesota,
Minneapolis,
Minnesota,
United States.
April 01, 2013.
Hallstrom, T. C., (Author & Presenter)
"Rb/E2F1 & Akt: How do cells distinguish 'normal' growth from oncogenic stimulation?",
Health and Biological Research (HBR) faculty research seminar - presented to undergrads pursuing science,
University of Minnesota,
Minneapolis,
Minnesota,
United States.
March 01, 2013.
Lu, H., (Author & Presenter), Hallstrom, T. C., (Author & Presenter)
"Control by the Rb/E2F, FoxO and P13K Pathways in Retinoblastoma",
Keystone Symposia - P13-Kinase and Interplay with Other Signaling Pathways,
Keystone,
Colorado,
United States.
February 24, 2013.
Hallstrom, T. C., (Author & Presenter)
"Interaction between Rb and and Pten in Retinoblastoma.",
Translational Therapy Meeting,
University of Minnesota,
Minneapolis,
Minnesota,
United States.
July 01, 2012.
Lu, H., (Author & Presenter), Hallstrom, T. C., (Author & Presenter)
"Life and death decision by E2F1 depends on Jab1 mediated expression of E2F apoptoic but not DNA replication targets",
Second AACR International Conference on Frontiers in Basic Cancer Research,
San Francisco,
California,
United States.
September 14, 2011.
Hallstrom, T. C., (Author & Presenter)
"Jab1/CSN5 mediates E2F dependent expression of mitotic and apoptoic but not DNA replication targets",
Keystone Symposia - Stem Cells and Cancer (C4),
Keystone,
Colorado,
United States.
March 06, 2011.
Hallstrom, T. C., (Author & Presenter)
"RB1/PTEN interactions in Osteosarcoma",
University of Minnesota Sarcoma Group Meeting,
Minneapolis,
Minnesota,
United States.
April 01, 2010.
Hallstrom, T. C., (Author & Presenter)
"Coordinate regulation of E2F1 apoptoic function by P13K",
Genetic mechanisms of Cancer Seminar,
University of Minnesota,
Minneapolis,
Minnesota,
United States.
April 01, 2010.
Hallstrom, T. C., (Author & Presenter)
"RB1/PTEN interactions in Osteosarcoma",
University of Minnesota Sarcoma retreat,
University of Minnesota,
Minneapolis,
Minnesota,
United States.
March 01, 2010.
Hallstrom, T. C., (Author & Presenter)
"Linking P13K Activity to E2F1 Control",
Translational Therapy Meeting,
University of Minnesota,
Minneapolis,
Minnesota,
United States.
August 01, 2009.
Hallstrom, T. C., (Author & Presenter)
"P13K regulates Jab1/E2F1 induction of apoptoic target genes in cancer",
Keystone Symposia - Deregulation of Transcription in Cancer (E2),
Killarney,
Ireland.
June 21, 2009.
Hallstrom, T. C., (Author & Presenter), Mori, S., (Author & Presenter), Nevins, J., (Author & Presenter)
"P13K Repression of an E2F1-Dependent Apoptoic Gene Expression Program in Cancer",
Keystone Symposia - Cell Death & Cell Senescence (J8),
Keystone,
Colorado,
United States.
February 07, 2008.
Hallstrom, T. C., (Author & Presenter)
"E2F1 & P13K: How do cells distinguish 'normal' growth from oncogenic stimulation?",
Invited alumni seminar,
Bethel University,
St. Paul,
Minnesota,
United States.
January 01, 2008.
Hallstrom, T. C., (Author & Presenter)
"Regulation of Rb/E2F in Cancer",
Cancer Center Seminar,
University of Minnesota,
Minneapolis,
Minnesota,
United States.
November 01, 2007.
Hallstrom, T. C., (Author & Presenter)
"Regulation of Rb/E2f in Cancer",
Genetic Mechanisms of Cancer Seminar,
University of Minnesota,
Minneapolis,
Minnesota,
United States.
October 01, 2007.
Contact
Contact
Address
Pediatric Blood and Marrow Transplantation & Cellular TherapyMayo Mail Code 366
420 Delaware Street SE
Minneapolis, MN 55455