Sara Hamilton Hart, PhD

Assistant Professor, Department of Laboratory Medicine and Pathology

Sara Hamilton Hart

Contact Info

hamil062@umn.edu

Office Phone 612-625-1626

Mailing Address:
WMBB
2641D
2101 6th St SE
Minneapolis, MN 55455

PhD, University of Iowa (Immunology), 1998-2003

Knox College, Galesburg, IL (Biochemistry), 1994-1998

Summary

Dr. Hamilton is a research immunologist and is focusing her research on CD8+ T cells with the goal of learning how to manipulate them to elicit the optimal protective immune response to pathogen infection. She is currently working in two different model systems: mice that have been naturally exposed to environmental microbes to gain a better understanding of T-cell function in these mice, and mice exposed to malaria to gain a better understanding of T-cell activity during severe cerebral complications of the disease.

Awards & Recognition

Leukemia and Lymphoma Special Fellow, 2009-2012
American Cancer Society Fellow- Supplement Award, 2005-2008
American Cancer Society Fellow, 2005-2008

Professional Associations

American Association of Immunologists, member, 2012-present

Research

Research Summary/Interests

For many years immunologists have experimented with genetically inbred mice housed in clean quarantined facilities. These facilities protect experimental mice from exposure to environmental pathogens, including viruses that humans are exposed to in daily life. Hamilton and co-investigators have conducted research in which they house pathogen-free inbred mice with mice from pet stores that carry environmental microbes, and then track CD8+ T cell behavior both in the pet store mice and in the inbred mice housed with them. In the pilot study, they characterized CD8+ T cell populations and distribution in various organs of environmentally exposed mice and found measurable differences compared to CD8+ T cells from environmentally protected inbred mice. The next step is to immunize the mice with different agents and compare CD8+ T cell responses. Preliminary data shows that environmentally exposed mice acquire increased levels of immune protection from some infectious microbes that inbred mice housed in clean facilities do not possess.

In her malaria studies, Hamilton uses a mouse model that mimics the human experience in development of cerebral malaria, a condition caused by specific malarial strains to which certain individuals are vulnerable, particularly children. During this infection CD8+ T cell populations traffic to the brains of experimental mice. These cells recognize antigen presented by brain endothelial cells and mount an attack, which can cause brain hemorrhages. The goal of the study is to find ways to inhibit or control CD8+ T cell activity in the brain through immune system modulation to prevent cerebral hemorrhaging. Hamilton and her colleagues have found that stimulation by specific cytokine therapy can dampen the CD8+ T cell response to triggering antigens in the brain.

Hamilton is also following up on earlier research that involved compartmentalizing CD8+ T cell memory cells into subset populations. She and her colleagues found a small subset that does not readily expand after antigen exposure, yet provides the most effective immune response to acute infection. She will delve deeper into how this specific subset of CD8+ memory T cells is created, how these cells can be more easily identified through specific cell-surface markers, how they function, and how they can be stimulated to expand, possibly through a vaccine strategy.

Publications

Interleukin-15 Complex Treatment Protects Mice from Cerebral Malaria by Inducing Interleukin-10-Producing Natural Killer Cells.
Burrack KS, Huggins MA, Taras E, Dougherty P, Henzler CM, Yang R, Alter S, Jeng EK, Wong HC, Felices M, Cichocki F, Miller JS, Hart GT, Johnson AJ, Jameson SC, Hamilton SE.
Immunity. 2018 Mar 20. pii: S1074-7613(18)30088-8. doi: 10.1016/j.immuni.2018.03.012. [Epub ahead of print] PMID: 29625893

IL-4 sensitivity shapes the peripheral CD8+ T cell pool and response to infection.  Renkema KR, Lee JY, Lee YJ, Hamilton SE, Hogquist KA, Jameson SC.  J Exp Med. 2016 Jun 27;213(7):1319-29. doi: 10.1084/jem.20151359. Epub 2016 Jun 13.  PMID: 27298446

Normalizing the environment recapitulates adult human immune traits in laboratory mice.
Beura LK, Hamilton SE, Bi K, Schenkel JM, Odumade OA, Casey KA, Thompson EA, Fraser KA, Rosato PC, Filali-Mouhim A, Sekaly RP, Jenkins MK, Vezys V, Haining WN, Jameson SC, Masopust D.
Nature. 2016 Apr 28;532(7600):512-6. doi: 10.1038/nature17655. Epub 2016 Apr 20.
PMID: 27096360

Effective effector generation of CD8+ T cells and NK cells: A need for T-bet and ZEB-too.
Hamilton SE, Jameson SC.
J Exp Med. 2015 Nov 16;212(12):1990. doi: 10.1084/jem.21212insight3. No abstract available.
PMID: 26573585

Targeting glutamine metabolism rescues mice from late-stage cerebral malaria.
Gordon EB, Hart GT, Tran TM, Waisberg M, Akkaya M, Kim AS, Hamilton SE, Pena M, Yazew T, Qi CF, Lee CF, Lo YC, Miller LH, Powell JD, Pierce SK.
Proc Natl Acad Sci U S A. 2015 Oct 20;112(42):13075-80. doi: 10.1073/pnas.1516544112. Epub 2015 Oct 5.
PMID: 26438846

The TCR's sensitivity to self peptide-MHC dictates the ability of naive CD8(+) T cells to respond to foreign antigens.
Fulton RB, Hamilton SE, Xing Y, Best JA, Goldrath AW, Hogquist KA, Jameson SC.
Nat Immunol. 2015 Jan;16(1):107-17. doi: 10.1038/ni.3043. Epub 2014 Nov 24.
PMID: 25419629

Cutting edge: The signals for the generation of T cell memory are qualitatively different depending on TCR ligand strength.
Knudson KM, Hamilton SE, Daniels MA, Jameson SC, Teixeiro E.
J Immunol. 2013 Dec 15;191(12):5797-801. doi: 10.4049/jimmunol.1300905. Epub 2013 Nov 15.
PMID: 24244018  

Virtual memory CD8 T cells display unique functional properties.
Lee JY, Hamilton SE, Akue AD, Hogquist KA, Jameson SC.
Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13498-503. doi: 10.1073/pnas.1307572110. Epub 2013 Jul 29.
PMID: 23898211

Effector-like CD8+ T cells in the memory population mediate potent protective immunity.
Olson JA, McDonald-Hyman C, Jameson SC, Hamilton SE.
Immunity. 2013 Jun 27;38(6):1250-60. doi: 10.1016/j.immuni.2013.05.009. Epub 2013 Jun 6.
PMID: 23746652

Minicircle DNA is superior to plasmid DNA in eliciting antigen-specific CD8+ T-cell responses.
Dietz WM, Skinner NE, Hamilton SE, Jund MD, Heitfeld SM, Litterman AJ, Hwu P, Chen ZY, Salazar AM, Ohlfest JR, Blazar BR, Pennell CA, Osborn MJ.
Mol Ther. 2013 Aug;21(8):1526-35. doi: 10.1038/mt.2013.85. Epub 2013 May 21.
PMID: 23689601

CD8 T cell memory: it takes all kinds.
Hamilton SE, Jameson SC.
Front Immunol. 2012 Nov 27;3:353. doi: 10.3389/fimmu.2012.00353. eCollection 2012.
PMID: 23230436

Cutting edge: Kruppel-like factor 2 is required for phenotypic maintenance but not development of B1 B cells.
Hart GT, Peery SL, Hamilton SE, Jameson SC.
J Immunol. 2012 Oct 1;189(7):3293-7. Epub 2012 Aug 31.
PMID: 22942434

CD8 T cell quiescence revisited.
Hamilton SE, Jameson SC.
Trends Immunol. 2012 May;33(5):224-30. doi: 10.1016/j.it.2012.01.007. Epub 2012 Feb 21. Review.
PMID: 22361353

Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination.
Olvera-Gomez I, Hamilton SE, Xiao Z, Guimaraes CP, Ploegh HL, Hogquist KA, Wang L, Jameson SC.
Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):2072-7. doi:10.1073/pnas.1105771109. Epub 2012 Jan 23.
PMID: 22308317

IL-2 complex treatment can protect naive mice from bacterial and viral infection.
Hamilton SE, Schenkel JM, Akue AD, Jameson SC.
J Immunol. 2010 Dec 1;185(11):6584-90. doi: 10.4049/jimmunol.1001215. Epub 2010 Oct 29.
PMID: 21037095

CD4+CD25+Foxp3+ regulatory T cells optimize diversity of the conventional T cell repertoire during reconstitution from lymphopenia.
Winstead CJ, Reilly CS, Moon JJ, Jenkins MK, Hamilton SE, Jameson SC, Way SS, Khoruts A.
J Immunol. 2010 May 1;184(9):4749-60. doi: 10.4049/jimmunol.0904076. Epub 2010 Mar 31.
PMID: 20357265

The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion.
Haluszczak C, Akue AD, Hamilton SE, Johnson LD, Pujanauski L, Teodorovic L, Jameson SC, Kedl RM.
J xp Med. 2009 Feb 16;206(2):435-48. doi: 10.1084/jem.20081829. Epub 2009 Feb 2.
PMID: 19188498 

Different T cell receptor signals determine CD8+ memory versus effector development.
Teixeiro E, Daniels MA, Hamilton SE, Schrum AG, Bragado R, Jameson SC, Palmer E.
Science. 2009 Jan 23;323(5913):502-5. doi: 10.1126/science.1163612.
PMID: 19164748

The nature of the lymphopenic environment dictates protective function of homeostatic-memory CD8+ T cells.
Hamilton SE, Jameson SC.
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18484-9. doi: 10.1073/pnas.0806487105. Epub 2008 Nov 19.
PMID: 19020089

CD8(+) T cell differentiation: choosing a path through T-bet.
Hamilton SE, Jameson SC.
Immunity. 2007 Aug;27(2):180-2.
PMID: 17723210

Listeriolysin O-deficient Listeria monocytogenes as a vaccine delivery vehicle: antigen-specific CD8 T cell priming and protective immunity.
Hamilton SE
, Badovinac VP, Khanolkar A, Harty JT.
J Immunol. 2006 Sep 15;177(6):4012-20.
PMID: 16951364

The generation of protective memory-like CD8+ T cells during homeostatic proliferation requires CD4+ T cells.
Hamilton SE, Wolkers MC, Schoenberger SP, Jameson SC.
Nat Immunol. 2006 May;7(5):475-81. Epub 2006 Apr 9.
PMID: 16604076

Environmental conservation: bystander CD4 T cells keep CD8 memories fresh.
Hamilton SE, Prlic M, Jameson SC.
Nat Immunol. 2004 Sep;5(9):873-4. No abstract available.
PMID: 15334079

Neutrophil involvement in cross-priming CD8+ T cell responses to bacterial antigens.
Tvinnereim AR, Hamilton SE, Harty JT.
J Immunol. 2004 Aug 1;173(3):1994-2002.
PMID: 15265934

MHC class Ia-restricted memory T cells inhibit expansion of a nonprotective MHC class Ib (H2-M3)-restricted memory response.
Hamilton SE
, Porter BB, Messingham KA, Badovinac VP, Harty JT.
Nat Immunol. 2004 Feb;5(2):159-68. Epub 2004 Jan 25.
PMID: 14745446

Regulation of CD8+ T cells undergoing primary and secondary responses to infection in the same host.
Badovinac VP, Messingham KA, Hamilton SE, Harty JT.
J Immunol. 2003 May 15;170(10):4933-42.
PMID: 12734336

Viral infection results in massive CD8+ T cell expansion and mortality in vaccinated perforin-deficient mice.
Badovinac VP, Hamilton SE, Harty JT.
Immunity. 2003 Apr;18(4):463-74.
PMID: 12705850

Quantitation of CD8+ T cell expansion, memory, and protective immunity after immunization with peptide-coated dendritic cells.
Hamilton SE
, Harty JT.
J Immunol. 2002 Nov 1;169(9):4936-44.
PMID: 12391206

CD8(+)-T-cell response to secreted and nonsecreted antigens delivered by recombinant Listeria monocytogenes during secondary infection.
Tvinnereim AR, Hamilton SE, Harty JT.
Infect Immun. 2002 Jan;70(1):153-62.
PMID: 11748177

Listeria monocytogenes infection overcomes the requirement for CD40 ligand in exogenous antigen presentation to CD8(+) T cells.
Hamilton SE
, Tvinnereim AR, Harty JT.
J Immunol. 2001 Nov 15;167(10):5603-9.
PMID:11698431